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Wei L, Ding E, Lu D, Rui Z, Shen J, Fan G. Assessing the effect of modifiable risk factors on hepatocellular carcinoma: evidence from a bidirectional Mendelian randomization analysis. Discov Oncol 2025; 16:437. [PMID: 40164825 PMCID: PMC11958933 DOI: 10.1007/s12672-025-02177-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 03/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND The pathogenesis of hepatocellular carcinoma (HCC) involves a variety of environmental risk factors, some of which have yet to be fully clarified. Using the Mendelian randomization (MR) approach, this study comprehensively investigates the causal effect of genetically predicted modifiable risk factors on HCC. METHODS Genetic variants related to the 50 risk factors that had been identified in previous research were derived from genome-wide association studies. Summary statistics for the discovery cohort and validation cohort of HCC were sourced from the FinnGen consortium and the UK Biobank, respectively. Bidirectional MR analysis and sensitivity analysis were performed to establish causative risk factors for HCC. RESULTS Through the inverse variance weighted method, the results of the discovery cohort indicated that waist circumference, nonalcoholic fatty liver disease (NAFLD), alanine aminotransferase (ALT) levels, and aspartate aminotransferase (AST) levels were significantly linked to HCC occurrence risk. Furthermore, body fat percentage, glycated hemoglobin (HbA1c), obesity class 1-3, waist-to-hip ratio, iron, ferritin, transferrin saturation, and urate had suggestive associations with HCC. The validation cohort further confirmed that NAFLD and ALT levels were strongly related to HCC. Reverse MR indicated that genetic susceptibility to HCC was connected to NAFLD and transferrin saturation. Sensitivity analyses showed that most of the findings were robust. CONCLUSION This MR study delivers evidence of the complex causal relationship between modifiable risk factors and HCC. These findings offer new insights into potential prevention and treatment strategies for HCC.
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Affiliation(s)
- Lijuan Wei
- Department of Nuclear Medicine, Tianjin First Central Hospital, Tianjin, China
| | - Enci Ding
- Department of Nuclear Medicine, Tianjin First Central Hospital, Tianjin, China
| | - Dongyan Lu
- Department of Nuclear Medicine, Tianjin First Central Hospital, Tianjin, China
| | - Zhongying Rui
- Department of Nuclear Medicine, Tianjin First Central Hospital, Tianjin, China
| | - Jie Shen
- Department of Nuclear Medicine, Tianjin First Central Hospital, Tianjin, China
| | - Guoju Fan
- Department of Vascular Surgery, The Second Hospital of Tianjin Medical University, No. 23, Pingjiang Road, Hexi District, Tianjin, 300211, China.
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Li Y, Shu J, Tan P, Dong X, Zhang M, He T, Yang Z, Zhang X, Giovannucci EL, Liu Z, Zhou Z, Li Q, Xu Y, Xu X, Peng T, Lu J, Zhang Y, Zhu H, Fang A. Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study. Br J Nutr 2024; 132:1411-1422. [PMID: 39506332 DOI: 10.1017/s0007114524001776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2024]
Abstract
Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.
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Affiliation(s)
- Yunshan Li
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jing Shu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Peishan Tan
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xiaocong Dong
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Mingjie Zhang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Tongtong He
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zhijun Yang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xuehong Zhang
- Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Yale University School of Nursing, Orange, CT, USA
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Zhaoyan Liu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zhongguo Zhou
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Qijiong Li
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yanjun Xu
- Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People's Republic of China
| | - Xiaojun Xu
- Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People's Republic of China
| | - Tianyou Peng
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jialin Lu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Yaojun Zhang
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Huilian Zhu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Aiping Fang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
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Polpichai N, Saowapa S, Danpanichkul P, Chan SY, Sierra L, Blagoie J, Rattananukrom C, Sripongpun P, Kaewdech A. Beyond the Liver: A Comprehensive Review of Strategies to Prevent Hepatocellular Carcinoma. J Clin Med 2024; 13:6770. [PMID: 39597914 PMCID: PMC11594971 DOI: 10.3390/jcm13226770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/06/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND/OBJECTIVES Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily developing in the context of chronic liver disease. Traditional prevention has focused on liver-specific interventions like antiviral therapies and surveillance. However, extrahepatic factors also significantly contribute to HCC risk. This review explores comprehensive strategies for HCC prevention, including both hepatic and extrahepatic factors. METHODS An extensive literature search of peer-reviewed articles up to October 2024 was conducted, focusing on studies addressing HCC prevention strategies. Studies that focused on both hepatic and extrahepatic factors were included. Data were extracted and synthesized to provide an overview of current prevention strategies and their effectiveness in reducing HCC incidence. RESULTS Hepatitis B vaccination and antiviral treatments for hepatitis B and C significantly reduce HCC incidence. Lifestyle modifications-such as reducing alcohol consumption, maintaining a healthy weight through diet and exercise, and smoking cessation-are crucial in lowering HCC risk. Environmental measures to limit exposure to aflatoxins and other hazards also contribute to prevention. Regular surveillance of high-risk groups enables early detection and improves survival rates. Emerging strategies like immunotherapy and gene therapy show potential for further reducing HCC risk. CONCLUSIONS A comprehensive approach combining medical interventions, lifestyle changes, and environmental controls is essential for effectively decreasing HCC incidence globally. Implementing these combined measures could significantly reduce the global burden of HCC.
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Affiliation(s)
- Natchaya Polpichai
- Department of Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA; (N.P.); (S.-Y.C.); (J.B.)
| | - Sakditad Saowapa
- Department of Medicine, Texas Tech University Health Science Center, Lubbock, TX 79430, USA; (S.S.); (P.D.)
| | - Pojsakorn Danpanichkul
- Department of Medicine, Texas Tech University Health Science Center, Lubbock, TX 79430, USA; (S.S.); (P.D.)
| | - Shu-Yen Chan
- Department of Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA; (N.P.); (S.-Y.C.); (J.B.)
| | - Leandro Sierra
- Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA;
| | - Johanna Blagoie
- Department of Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA; (N.P.); (S.-Y.C.); (J.B.)
| | - Chitchai Rattananukrom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen 40002, Thailand;
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
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Liu Z, Yuan H, Suo C, Zhao R, Jin L, Zhang X, Zhang T, Chen X. Point-based risk score for the risk stratification and prediction of hepatocellular carcinoma: a population-based random survival forest modeling study. EClinicalMedicine 2024; 75:102796. [PMID: 39263676 PMCID: PMC11388332 DOI: 10.1016/j.eclinm.2024.102796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 09/13/2024] Open
Abstract
Background The precise associations between common clinical biomarkers and hepatocellular carcinoma (HCC) risk remain unclear but hold valuable insights for HCC risk stratification and prediction. Methods We examined the linear and nonlinear associations between the baseline levels of 32 circulating biomarkers and HCC risk in the England cohort of UK Biobank (UKBB) (n = 397,702). The participants were enrolled between 2006 and 2010 and followed up to 31st October 2022. The primary outcome is incident HCC cases. We then employed random survival forests (RSF) to select the top ten most informative biomarkers, considering their association with HCC, and developed a point-based risk score to predict HCC. The performance of the risk score was evaluated in three validation sets including UKBB Scotland and Wales cohort (n = 52,721), UKBB non-White-British cohort (n = 29,315), and the Taizhou Longitudinal Study in China (n = 17,269). Findings Twenty-five biomarkers were significantly associated with HCC risk, either linearly or nonlinearly. Based on the RSF model selected biomarkers, our point-based risk score showed a concordance index of 0.866 in the England cohort and varied between 0.814 and 0.849 in the three validation sets. HCC incidence rates ranged from 0.95 to 30.82 per 100,000 from the lowest to the highest quintiles of the risk score in the England cohort. Individuals in the highest risk quintile had a 32-73 times greater risk of HCC compared to those in the lowest quintile. Moreover, over 70% of HCC cases were detected in individuals within the top risk score quintile across all cohorts. Interpretation Our simple risk score enables the identification of high-risk individuals of HCC in the general population. However, including some biomarkers, such as insulin-like growth factor 1, not routinely measured in clinical practice may increase the model's complexity, highlighting the need for more accessible biomarkers that can maintain or improve the predictive accuracy of the risk score. Funding This work was supported by the National Natural Science Foundation of China (grant numbers: 82204125) and the Science and Technology Support Program of Taizhou (TS202224).
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Affiliation(s)
- Zhenqiu Liu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Huangbo Yuan
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Renjia Zhao
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Li Jin
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Yale University School of Nursing, Orange, CT, USA
| | - Tiejun Zhang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, China
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Cho Y, Kim BH, Park JW. Preventive strategy for nonalcoholic fatty liver disease-related hepatocellular carcinoma. Clin Mol Hepatol 2023; 29:S220-S227. [PMID: 36353768 PMCID: PMC10029950 DOI: 10.3350/cmh.2022.0360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 09/05/2022] [Indexed: 11/12/2022] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, including Asia. Most patients with NAFLD-related HCC are at a much-advanced stage and older age at the time of diagnosis than those with virus-related HCC because they have not undergone HCC surveillance. This review provides an overview of the mechanism of hepatocarcinogenesis in NAFLD, preventive strategies for NAFLDrelated HCC, and strategies for the surveillance of patients with NAFLD.
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Affiliation(s)
- Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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Bone Densities Assessed by Hounsfield Units at L5 in Computed Tomography Image Independently Predict Hepatocellular Carcinoma Development in Cirrhotic Patients. J Clin Med 2022; 11:jcm11195562. [PMID: 36233438 PMCID: PMC9573236 DOI: 10.3390/jcm11195562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 09/12/2022] [Accepted: 09/20/2022] [Indexed: 11/24/2022] Open
Abstract
A previous study identified that bone density (BD) assessed by Hounsfield unit (HU) at T12 in computed tomography (CT) image was a predictor for hepatocellular carcinoma (HCC) development in cirrhotic patients. Here, we conducted a verification study, where clinical variables together with BDs (assessed from three different bone areas: T12, L5, and femur trochanter) were assessed for their predictive values for time-to-HCC development in cirrhotic patients. Univariate Cox proportional hazard analysis showed that age (p = 0.017), T12 BD (p = 0.013) and L5 BD (p = 0.005), but not femur BD, were significant predictors. Multivariate analysis revealed that L5 BD was the only independent factor associated with time-to-HCC development (adjusted p = 0.007). Kaplan-Meier analysis confirmed that BD which was lower than median HU was associated with a shorter time-to-HCC development for both T12 BD and L5 BD (p = 0.001 each). Longitudinal follow-ups for BDs in HCC patients having received serial CT imaging studies unveiled a significantly rapid reduction in BD, right before HCC was diagnosed (p = 0.025 when compared with the average BD reduction rate). In conclusion, BD assessed by HU at L5 was an independent predictor for HCC development in cirrhotic patients. Rapid BD reduction during CT scan follow-ups could serve as a warning sign for HCC development.
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Huang Y, Yuan Y, Chen S, Xu D, Xiao L, Wang X, Qin W, Liu B. Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19. Front Immunol 2022; 13:985781. [PMID: 36275701 PMCID: PMC9583923 DOI: 10.3389/fimmu.2022.985781] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 08/01/2022] [Indexed: 11/16/2022] Open
Abstract
Coronavirus disease 2019 (COVID‐19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.
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Affiliation(s)
- Yongbiao Huang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ye Yuan
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sheng Chen
- Department of general surgery, Shangrao People's Hospital, Shangrao, China
| | - Duo Xu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lingyan Xiao
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xi Wang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wan Qin
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Liu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Bo Liu,
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Ravaioli F, Pivetti A, Di Marco L, Chrysanthi C, Frassanito G, Pambianco M, Sicuro C, Gualandi N, Guasconi T, Pecchini M, Colecchia A. Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease. Int J Mol Sci 2022; 23:ijms23169016. [PMID: 36012285 PMCID: PMC9409132 DOI: 10.3390/ijms23169016] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/09/2022] [Accepted: 08/11/2022] [Indexed: 12/12/2022] Open
Abstract
Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the different liver etiologies and the condition of advanced chronic liver disease (cirrhosis) with related complications. To date, patients with liver disease, regardless of underlying etiology, have been shown to have reduced levels of vitamin D. There is also evidence of the predictive role of vitamin D values in complications and progression of advanced disease. However, specific indications of vitamin D supplementation are not conclusive concerning what is already recommended in the general population. Future studies should make an effort to unify and validate the role of vitamin D supplementation in chronic liver disease.
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Affiliation(s)
- Federico Ravaioli
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
- Department of Medical and Surgical Sciences, University of Bologna, 40128 Bologna, Italy
- Correspondence:
| | - Alessandra Pivetti
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Lorenza Di Marco
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Christou Chrysanthi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Gabriella Frassanito
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Martina Pambianco
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Chiara Sicuro
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Noemi Gualandi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Tomas Guasconi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Maddalena Pecchini
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
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Cisneros-Garza L, González-Huezo M, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño G, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez M, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva J, Gabutti-Thomas J, Guerrero-Ixtlahuac J, Higuera-de-la-Tijera F, Huitzil-Meléndez D, Kimura-Hayama E, López-Hernández P, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz M, Ruíz-García E, Sánchez-Ávila J, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:216-234. [DOI: 10.1016/j.rgmxen.2021.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/21/2021] [Indexed: 12/24/2022] Open
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10
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Cisneros-Garza LE, González-Huezo MS, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño GA, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez MA, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva JA, Gabutti-Thomas JA, Guerrero-Ixtlahuac J, Higuera-de-la-Tijera F, Huitzil-Meléndez D, Kimura-Hayama E, López-Hernández PA, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz MA, Ruíz-García E, Sánchez-Ávila JF, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:216-234. [PMID: 35431142 DOI: 10.1016/j.rgmx.2021.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/21/2021] [Indexed: 01/04/2025]
Abstract
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.
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Affiliation(s)
- L E Cisneros-Garza
- Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - C Moctezuma-Velázquez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - M Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - G A Álvarez-Treviño
- Unidad de Medicina de Alta Especialidad 25 IMSS, Monterrey, Nuevo León, Mexico
| | | | - L Bornstein-Quevedo
- InmunoQ, Laboratorio de Patología, Inmunohistoquímica y Biología Molecular, Mexico City, Mexico
| | | | | | | | | | | | - J A Gabutti-Thomas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - D Huitzil-Meléndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - P A López-Hernández
- Unidad de Medicina de Alta Especialidad 25 IMSS, Monterrey, Nuevo León, Mexico
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, Mexico
| | | | - M A Morales-Ruiz
- Centro Oncológico Estatal Issemym, Toluca, Estado de México, Mexico
| | - E Ruíz-García
- Instituto Nacional de Cancerología, Mexico City, Mexico
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, Mexico
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11
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Goto RL, Tablas MB, Prata GB, Espírito Santo SG, Fernandes AAH, Cogliati B, Barbisan LF, Romualdo GR. Vitamin D 3 supplementation alleviates chemically-induced cirrhosis-associated hepatocarcinogenesis. J Steroid Biochem Mol Biol 2022; 215:106022. [PMID: 34774723 DOI: 10.1016/j.jsbmb.2021.106022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 10/05/2021] [Accepted: 11/07/2021] [Indexed: 11/19/2022]
Abstract
Vitamin D3 (VD3) deficiency has been associated with increased risk for cirrhosis and hepatocellular carcinoma, a highly incident malignant neoplasia worldwide. On the other hand, VD3 supplementation has shown some beneficial effects in clinical studies and rodent models of chronic liver disease. However, preventive effects of dietary VD3 supplementation in cirrhosis-associated hepatocarcinogenesis is still unknow. To investigate this purpose, male Wistar rats submitted to a combined diethylnitrosamine- and thioacetamide-induced model were concomitantly supplemented with VD3 (5,000 and 10,000 IU/kg diet) for 25 weeks. Liver samples were collected for histological, biochemical and molecular analysis. Serum samples were used to measure 25-hydroxyvitamin D [25(OH)D] and alanine aminotransferase levels. Both VD3 interventions decreased hepatic collagen deposition and pro-inflammatory p65 protein levels, while increased hepatic antioxidant catalase and glutathione peroxidase activities and serum 25(OH)D, without a clear dose-response effect. Nonetheless, only the highest concentration of VD3 increased hepatic protein levels of VD receptor, while decreased the number of large preneoplastic glutathione-S-transferase- (>0.5 mm²) and keratin 8/18-positive lesions, as well the multiplicity of hepatocellular adenomas. Moreover, this intervention increased hepatic antioxidant Nrf2 protein levels and glutathione-S-transferase activity. In summary, dietary VD3 supplementation - in special the highest intervention - showed antifibrotic and antineoplastic properties in chemically-induced cirrhosis-associated hepatocarcinogenesis. The positive modulation of Nrf2 antioxidant axis may be mechanistically involved with these beneficial effects, and may guide future clinical studies.
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MESH Headings
- Adenoma, Liver Cell/chemically induced
- Adenoma, Liver Cell/metabolism
- Adenoma, Liver Cell/pathology
- Adenoma, Liver Cell/prevention & control
- Alanine Transaminase/blood
- Alanine Transaminase/genetics
- Animals
- Carcinoma, Hepatocellular/chemically induced
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/prevention & control
- Catalase/blood
- Catalase/genetics
- Chemoprevention/methods
- Collagen/genetics
- Collagen/metabolism
- Dietary Supplements
- Diethylnitrosamine/toxicity
- Gene Expression Regulation/drug effects
- Glutathione Peroxidase/blood
- Glutathione Peroxidase/genetics
- Glutathione Transferase/genetics
- Glutathione Transferase/metabolism
- Keratins/genetics
- Keratins/metabolism
- Liver/drug effects
- Liver/metabolism
- Liver/pathology
- Liver Cirrhosis/chemically induced
- Liver Cirrhosis/drug therapy
- Liver Cirrhosis/metabolism
- Liver Cirrhosis/pathology
- Liver Neoplasms/chemically induced
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Liver Neoplasms/prevention & control
- Male
- NF-E2-Related Factor 2/genetics
- NF-E2-Related Factor 2/metabolism
- Neoplasm Proteins/genetics
- Neoplasm Proteins/metabolism
- Nucleocytoplasmic Transport Proteins/genetics
- Nucleocytoplasmic Transport Proteins/metabolism
- Rats
- Rats, Wistar
- Receptors, Calcitriol/genetics
- Receptors, Calcitriol/metabolism
- Thioacetamide/toxicity
- Vitamin D/administration & dosage
- Vitamin D/analogs & derivatives
- Vitamin D/blood
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Affiliation(s)
- Renata L Goto
- São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil
| | - Mariana B Tablas
- São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil
| | - Gabriel B Prata
- São Paulo State University (UNESP), Medical School, Department of Pathology, Botucatu, SP, Brazil
| | - Sara G Espírito Santo
- São Paulo State University (UNESP), Medical School, Department of Pathology, Botucatu, SP, Brazil
| | - Ana Angélica H Fernandes
- São Paulo State University (UNESP), Biosciences Institute, Department of Chemical and Biological Sciences, Botucatu, SP, Brazil
| | - Bruno Cogliati
- University of São Paulo (USP), School of Veterinary Medicine and Animal Science, Department of Pathology, São Paulo, SP, Brazil
| | - Luis F Barbisan
- São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil
| | - Guilherme R Romualdo
- São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil; São Paulo State University (UNESP), Medical School, Department of Pathology, Botucatu, SP, Brazil.
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Alam W, Ullah H, Santarcangelo C, Di Minno A, Khan H, Daglia M, Arciola CR. Micronutrient Food Supplements in Patients with Gastro-Intestinal and Hepatic Cancers. Int J Mol Sci 2021; 22:8014. [PMID: 34360782 PMCID: PMC8347237 DOI: 10.3390/ijms22158014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 02/05/2023] Open
Abstract
Colorectal carcinogenesis is the second most common cause of mortality across all types of malignancies, followed by hepatic and stomach cancers. Chemotherapy and radiotherapy are key approaches to treating cancer patients, but these carry major concerns, such as a high risk of side effects, poor accessibility, and the non-selective nature of chemotherapeutics. A number of natural products have been identified as countering various forms of cancer with fewer side effects. The potential impact of vitamins and minerals on long-term health, cognition, healthy development, bone formation, and aging has been supported by experimental and epidemiological studies. Successful treatment may thus be highly influenced by the nutritional status of patients. An insufficient diet could lead to detrimental effects on immune status and tolerance to treatment, affecting the ability of chemotherapy to destroy cancerous cells. In recent decades, most cancer patients have been taking vitamins and minerals to improve standard therapy and/or to decrease the undesirable side effects of the treatment together with the underlying disease. On the other hand, taking dietary supplements during cancer therapy may affect the effectiveness of chemotherapy. Thus, micronutrients in complementary oncology must be selected appropriately and should be taken at the right time. Here, the potential impact of micronutrients on gastro-intestinal and hepatic cancers is explored and their molecular targets are laid down.
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Affiliation(s)
- Waqas Alam
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; (W.A.); (H.K.)
| | - Hammad Ullah
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
| | - Cristina Santarcangelo
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
| | - Alessandro Di Minno
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
- CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; (W.A.); (H.K.)
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| | - Carla Renata Arciola
- Laboratorio di Patologia delle Infezioni Associate all’Impianto, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via San Giacomo 14, 40136 Bologna, Italy
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13
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Adelani IB, Rotimi OA, Maduagwu EN, Rotimi SO. Vitamin D: Possible Therapeutic Roles in Hepatocellular Carcinoma. Front Oncol 2021; 11:642653. [PMID: 34113565 PMCID: PMC8185231 DOI: 10.3389/fonc.2021.642653] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 04/06/2021] [Indexed: 12/23/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a unique type of liver cancer instigated by underlying liver diseases. Pre-clinical evidence suggests that HCC progression, like other cancers, could be aided by vitamin D deficiency. Vitamin D is a lipid-soluble hormone usually obtained through sunlight. Vitamin D elucidates its biological responses by binding the vitamin D receptor; thus, promoting skeletal mineralization, and maintain calcium homeostasis. Other reported Vitamin D functions include specific roles in proliferation, angiogenesis, apoptosis, inflammation, and cell differentiation. This review highlighted studies on vitamin D's functional roles in HCC and discussed the specific therapeutic targets from various in vivo, in vitro and clinical studies over the years. Furthermore, it described recent advancements in vitamin D's anticancer effects and its metabolizing enzymes' roles in HCC development. In summary, the review elucidated specific vitamin D-associated target genes that play critical functions in the inhibition of tumorigenesis through inflammation, oxidative stress, invasion, and apoptosis in HCC progression.
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14
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Zhou J, Ge X, Fan X, Wang J, Miao L, Hang D. Associations of vitamin D status with colorectal cancer risk and survival. Int J Cancer 2021; 149:606-614. [PMID: 33783821 DOI: 10.1002/ijc.33580] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 12/11/2022]
Abstract
Biological evidence suggests that vitamin D has numerous anticancer functions, but the associations between vitamin D status and colorectal cancer (CRC) risk and survival remain inconclusive. Based on UK Biobank, we prospectively evaluated the associations of season-standardized 25-hydroxyvitamin D (25(OH)D) concentrations with CRC risk among 360 061 participants, and with survival among 2509 CRC cases. We observed an inverse linear relationship between 25(OH)D concentrations and CRC risk (P for linearity = .01; HR per 1-SD increment, 0.95; 95% CI, 0.91-0.99). Compared to the lowest quartile of 25(OH)D, the highest quartile was associated with a 13% (HR, 0.87; 95% CI, 0.77-0.98) lower risk of CRC. For CRC survival, compared to those in the lowest quartile of 25(OH)D, cases in the highest quartile had a 20% (HR, 0.80; 95% CI, 0.65-0.99) lower risk for overall death. Our findings indicate that higher concentrations of serum 25(OH)D are associated with lower incidence and improved survival of CRC, suggesting a role of vitamin D in the pathogenesis of CRC.
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Affiliation(s)
- Jian Zhou
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Xianxiu Ge
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Xikang Fan
- Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jiayu Wang
- Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Lin Miao
- Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Dong Hang
- Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
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15
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Yi Z, Wang L, Tu X. Effect of Vitamin D Deficiency on Liver Cancer Risk: A Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev 2021; 22:991-997. [PMID: 33906289 PMCID: PMC8325142 DOI: 10.31557/apjcp.2021.22.4.991] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 04/21/2021] [Indexed: 01/11/2023] Open
Abstract
Epidemiological studies have showed that vitamin D deficiency can increase the risk of liver cancers. Hence, we conducted a meta-analysis to explore the relationship between 25-hydroxyvitamin D [25(OH)D] levels and liver cancer risk. METHODS Cochrane Library, Medline, Web of Science, and Embase were searched up to Mar. 2020, and the references of those studies were also searched by hand. A meta-analysis of 11 studies was performed which met the inclusion criteria. Six case-control studies and five cohort studies were included. RESULTS A total of 11 studies (6 case-control and 5 cohort studies) with 12,895 incident cases were included in the meta-analysis. The meta-analysis showed that liver cancer risk was significantly increased for vitamin D deficiency, and the pooled RR and its 95% CIs was 2.16 (1.2, 3.88; P = 0.01). In comparative analyses between 25(OH)D levels in patients with hepatocellular carcinoma(HCC) and those in the control group individuals, the summary RR of liver cancer was -1.11 (95% CI=-1.96 to -0.25). The subgroup analysis of the different geographical region of the population showed that the risk of liver cancer in Asian subgroup, European subgroup and Egyptian subgroup increased for vitamin D deficiency (RR=1.34,95% CI 0.72 to 2.48, p <0.00001; RR=2.53,95% CI 1.62 to 3.93,p <0.0001;RR=29.5,95% CI 4.14 to 209.93, P=0.88). CONCLUSION The results of this meta-analysis indicate that vitamin D deficiency is associated with increased risk of liver cancer. The 25(OH)D3 levels are lower in HCC patients than those in health controls. Maintenance of sufficient serum vitamin D levels would be beneficial for prevention of liver cancer.
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Affiliation(s)
- Zhenghui Yi
- Department of General Surgery, Civil Aviation General Hospital, No.1 Gaojing, Chaoyang Street, Beijing, China.
| | - Linjie Wang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
| | - Xiangqun Tu
- Department of General Surgery, Civil Aviation General Hospital, No.1 Gaojing, Chaoyang Street, Beijing, China.
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16
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Non-Musculoskeletal Benefits of Vitamin D beyond the Musculoskeletal System. Int J Mol Sci 2021; 22:ijms22042128. [PMID: 33669918 PMCID: PMC7924658 DOI: 10.3390/ijms22042128] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/13/2021] [Accepted: 02/17/2021] [Indexed: 02/06/2023] Open
Abstract
Vitamin D, a fat-soluble prohormone, is endogenously synthesized in response to sunlight or taken from dietary supplements. Since vitamin D receptors are present in most tissues and cells in the body, the mounting understanding of the role of vitamin D in humans indicates that it does not only play an important role in the musculoskeletal system, but has beneficial effects elsewhere as well. This review summarizes the metabolism of vitamin D, the research regarding the possible risk factors leading to vitamin D deficiency, and the relationships between vitamin D deficiency and numerous illnesses, including rickets, osteoporosis and osteomalacia, muscle weakness and falls, autoimmune disorders, infectious diseases, cardiovascular diseases (CVDs), cancers, and neurological disorders. The system-wide effects of vitamin D and the mechanisms of the diseases are also discussed. Although accumulating evidence supports associations of vitamin D deficiency with physical and mental disorders and beneficial effects of vitamin D with health maintenance and disease prevention, there continue to be controversies over the beneficial effects of vitamin D. Thus, more well-designed and statistically powered trials are required to enable the assessment of vitamin D’s role in optimizing health and preventing disease.
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17
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Jang HY, Choi GH, Hwang SH, Jang ES, Kim JW, Ahn JM, Choi Y, Cho JY, Han HS, Lee J, Chung JW, Baeg JY, Jeong SH. Sarcopenia and visceral adiposity predict poor overall survival in hepatocellular carcinoma patients after curative hepatic resection. Transl Cancer Res 2021; 10:854-866. [PMID: 35116415 PMCID: PMC8799077 DOI: 10.21037/tcr-20-2974] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 11/27/2020] [Indexed: 12/15/2022]
Abstract
Background This study investigated the association of 3 components of body composition (sarcopenia, intramuscular fat deposition and visceral adiposity) with the overall or recurrence-free survival of hepatocellular carcinoma (HCC) patients who underwent curative hepatic resection. Methods One hundred sixty newly diagnosed and surgically treated HCC patients were retrospectively enrolled from 2003 to 2011. Three items of body composition were measured using the 3rd lumbar level image of preoperative computed tomography (CT): psoas muscle index (PMI), psoas muscle attenuation (PMA), and visceral adipose tissue index (VATI). Sex-specific optimal cut-off for each item was determined from receiver-operating characteristic curves. Results The HCC patients showed a median age of 55 years, 75% of male, 78% of hepatitis B surface antigen positivity, and 96% of Child-Pugh A. The sarcopenic group (PMI less than the sex-specific cutoff of 3.33 cm2/m2 for men and 2.38 cm2/m2 for women) had 17.5% of the patients with a lower PMA (more fat deposition) but similar VATI compared to the non-sarcopenic group. PMI showed a positive correlation with PMA (ρ=0.493, P<0.001), while there was no significant correlation between PMI and VATI, and between PMA and VATI. On the multivariate analysis, a high PMI and low VATI were independent factors affecting overall survival while PMA was not. Nevertheless, PMI and VATI were not independent factors for recurrence-free survival. Conclusions In curatively resected HCC patients, sarcopenia and high visceral adiposity predict poor overall survival but not recurrence-free survival, while PMA did not predict overall survival.
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Affiliation(s)
- Hee Yoon Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Gwang Hyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Sung Ho Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Joong Mo Ahn
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Youngrok Choi
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Jaebong Lee
- Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Jung Wha Chung
- Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo-si, Gyeonggi-do, Republic of Korea
| | - Joo Yeong Baeg
- Department of Internal Medicine, Sheikh khalifa Speciality Hospital, Ras al Khaimah, United Arab Emirates
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea
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Stepien M, Keski-Rahkonen P, Kiss A, Robinot N, Duarte-Salles T, Murphy N, Perlemuter G, Viallon V, Tjønneland A, Rostgaard-Hansen AL, Dahm CC, Overvad K, Boutron-Ruault MC, Mancini FR, Mahamat-Saleh Y, Aleksandrova K, Kaaks R, Kühn T, Trichopoulou A, Karakatsani A, Panico S, Tumino R, Palli D, Tagliabue G, Naccarati A, Vermeulen RCH, Bueno-de-Mesquita HB, Weiderpass E, Skeie G, Ramón Quirós J, Ardanaz E, Mokoroa O, Sala N, Sánchez MJ, Huerta JM, Winkvist A, Harlid S, Ohlsson B, Sjöberg K, Schmidt JA, Wareham N, Khaw KT, Ferrari P, Rothwell JA, Gunter M, Riboli E, Scalbert A, Jenab M. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study. Int J Cancer 2021; 148:609-625. [PMID: 32734650 DOI: 10.1002/ijc.33236] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 06/16/2020] [Accepted: 06/26/2020] [Indexed: 12/19/2022]
Abstract
Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
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Affiliation(s)
- Magdalena Stepien
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Pekka Keski-Rahkonen
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Agneta Kiss
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Nivonirina Robinot
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Talita Duarte-Salles
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Gabriel Perlemuter
- INSERM UMRS U996 - Intestinal Microbiota, Macrophages and Liver Inflammation, Clamart, France
- Université Paris-Sud, Clamart, France
- AP-HP, Hepato-gastroenterology and Nutrition, Antoine-Béclère Hospital, Clamart, France
| | - Vivian Viallon
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Anne Tjønneland
- Diet, Genes and Environment Unit, Danish Cancer Society Research Center, Copenhagen, Denmark
| | | | - Christina C Dahm
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Marie-Christine Boutron-Ruault
- CESP, Faculté de médecine-Université Paris-Sud, Faculté de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Francesca Romana Mancini
- CESP, Faculté de médecine-Université Paris-Sud, Faculté de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Yahya Mahamat-Saleh
- CESP, Faculté de médecine-Université Paris-Sud, Faculté de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Krasimira Aleksandrova
- Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anna Karakatsani
- Hellenic Health Foundation, Athens, Greece
- Second Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece
| | - Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, Provincial Health Authority (ASP) Ragusa, Ragusa, Italy
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy
| | - Giovanna Tagliabue
- Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessio Naccarati
- Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM) Torino, Torino, Italy
| | - Roel C H Vermeulen
- Institute of Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Hendrik Bastiaan Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Elisabete Weiderpass
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Guri Skeie
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | | | - Eva Ardanaz
- Navarra Public Health Institute, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Olatz Mokoroa
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain
| | - Núria Sala
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain
| | - Maria-Jose Sánchez
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. Granada. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - José María Huerta
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain
| | - Anna Winkvist
- The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Department of Public Health and Clinical Medicine, Nutrition Research, Umeå University, Umeå, Sweden
| | - Sophia Harlid
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Bodil Ohlsson
- Skåne University Hospital, Department of Internal Medicine, Lund University, Malmö, Sweden
| | - Klas Sjöberg
- Skåne University Hospital, Department of Gastroenterology and Nutrition, Lund University, Malmö, Sweden
| | - Julie A Schmidt
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Nick Wareham
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Kay-Tee Khaw
- University of Cambridge, School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Pietro Ferrari
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Joseph A Rothwell
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Institut Gustave Roussy, Villejuif, France
| | - Marc Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Augustin Scalbert
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
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19
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Kusnik A, Hunter N, Rasbach E, Miethke T, Reissfelder C, Ebert MP, Teufel A. Co-Medication and Nutrition in Hepatocellular Carcinoma: Potentially Preventative Strategies in Hepatocellular Carcinoma. Dig Dis 2021; 39:526-533. [PMID: 33429390 DOI: 10.1159/000514277] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 01/11/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, with about 841,000 new cases and 782,000 deaths annually. Given the clearly defined population at risk, mostly patients with liver cirrhosis, prevention of HCC could be highly effective. SUMMARY Besides regular ultrasound surveillance, numerous publications have suggested protective effects of diverse drugs and nutrients. However, none of those preventive options has made it into clinical routine or practice guidelines. We therefore summarize the current status of preventive effects of drugs such as statins, acetylsalicylic acid (ASA), and metformin, but also dietary aspects and nutrients such as coffee, tea, and vitamin D supplementation. A successful implementation of some of these strategies may potentially lead to improved prevention of HCC development in patients with liver cirrhosis. Key Messages: Accumulating data suggest that particularly ASA, antidiabetic therapies, and statins may substantially decrease HCC incidence in patients at risk.
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Affiliation(s)
- Alexander Kusnik
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,Center for Preventive Medicine and Digital Health Baden-Württemberg (CPDBW), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Nicole Hunter
- Institute of Medical Microbiology and Hygiene, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Erik Rasbach
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Thomas Miethke
- Institute of Medical Microbiology and Hygiene, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias Philip Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,Center for Preventive Medicine and Digital Health Baden-Württemberg (CPDBW), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Teufel
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,Center for Preventive Medicine and Digital Health Baden-Württemberg (CPDBW), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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20
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Li S, Saviano A, Erstad DJ, Hoshida Y, Fuchs BC, Baumert T, Tanabe KK. Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges. J Clin Med 2020; 9:E3817. [PMID: 33255794 PMCID: PMC7760293 DOI: 10.3390/jcm9123817] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/11/2020] [Accepted: 11/17/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high risk of developing HCC. Primary prevention seeks to eliminate cancer predisposing risk factors while tertiary prevention aims to prevent HCC recurrence. Secondary prevention targets patients with baseline chronic liver disease. Various epidemiological and experimental studies have identified candidates for secondary prevention-both etiology-specific and generic prevention strategies-including statins, aspirin, and anti-diabetic drugs. The introduction of multi-cell based omics analysis along with better characterization of the hepatic microenvironment will further facilitate the identification of targets for prevention. In this review, we will summarize HCC risk factors, pathogenesis, and discuss strategies of HCC prevention. We will focus on secondary prevention and also discuss current challenges in translating experimental work into clinical practice.
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Affiliation(s)
- Shen Li
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
| | - Antonio Saviano
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, 67000 Strasbourg, France;
| | - Derek J. Erstad
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
| | - Yujin Hoshida
- Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Department of Internal Medicine, Dallas, TX 75390, USA;
| | - Bryan C. Fuchs
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
| | - Thomas Baumert
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, 67000 Strasbourg, France;
| | - Kenneth K. Tanabe
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
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21
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Motomura T, Uchiyama H, Iguchi T, Ninomiya M, Yoshida R, Honboh T, Sadanaga N, Akashi T, Matsuura H. Impact of Osteopenia on Oncologic Outcomes After Curative Resection for Pancreatic Cancer. In Vivo 2020; 34:3551-3557. [PMID: 33144467 DOI: 10.21873/invivo.12198] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/28/2020] [Accepted: 09/29/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND/AIM We evaluated the relationship between low bone mineral density (BMD), also called osteopenia, and prognosis in patients who underwent resection for pancreatic cancer (PC). PATIENTS AND METHODS We enrolled 91 consecutive patients who underwent curative resections for PC between May 2009 and January 2019. Their BMDs were measured at the Th11 vertebra using computed tomography. Patients were then divided by age-adjusted standard BMD values into the osteopenia group (n=34) and the non-osteopenia group (n=57). Their overall survival (OS) and recurrence-free survival (RFS) were compared (log-rank test). RESULTS The two groups did not differ in age, BMI, tumor marker, operation time, blood loss, postoperative complications or stage. The osteopenia group had significantly worse 3-year rates for OS (46% vs. 30%, p=0.04) and RFS (41% vs. 26%, p=0.01). In multivariate analysis, osteopenia was an independent prognostic factor for RFS (HR=2.16, p=0.01). CONCLUSION Osteopenia is an adverse prognostic factor for patients with resected PC.
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Affiliation(s)
- Takashi Motomura
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Hideaki Uchiyama
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Tomohiro Iguchi
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Mizuki Ninomiya
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Rintaro Yoshida
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Takuya Honboh
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Noriaki Sadanaga
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Tetsuro Akashi
- Department of Internal Medicine, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
| | - Hiroshi Matsuura
- Department of Surgery, Saiseikai Fukuoka, General Hospital, Fukuoka, Japan
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22
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Simon TG, Chan AT. Lifestyle and Environmental Approaches for the Primary Prevention of Hepatocellular Carcinoma. Clin Liver Dis 2020; 24:549-576. [PMID: 33012445 PMCID: PMC7536356 DOI: 10.1016/j.cld.2020.06.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Patients with chronic liver disease are at increased risk of developing hepatocellular carcinoma (HCC). Most patients diagnosed with HCC have limited treatment options and a poor overall prognosis, with a 5-year survival less than 15%. Preventing the development of HCC represents the most important strategy. However, current guidelines lack specific recommendations for primary prevention. Lifestyle factors may be central in the pathogenesis of HCC, and primary prevention strategies focused on lifestyle modification could represent an important approach to the prevention of HCC. Both experimental and epidemiologic studies have identified promising chemopreventive agents for the primary prevention of HCC.
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Affiliation(s)
- Tracey G. Simon
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA
| | - Andrew T. Chan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston MA,Broad Institute, Boston MA,Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston MA
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23
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Sarcopenia associates with increased risk of hepatocellular carcinoma among male patients with cirrhosis. Clin Nutr 2020; 39:3132-3139. [DOI: 10.1016/j.clnu.2020.01.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 01/20/2020] [Accepted: 01/28/2020] [Indexed: 02/07/2023]
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24
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Liu H, Jiang X, Qiao Q, Chen L, Matsuda K, Jiang G, Yu T, Wang Y, Lin H, Liang X, Cai X. Association of circulating 25-Hydroxyvitamin D and its related genetic variations with hepatocellular carcinoma incidence and survival. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1080. [PMID: 33145299 PMCID: PMC7575935 DOI: 10.21037/atm-20-1637] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Vitamin D plays a key role of anti-cancer process, however, the association of vitamin D level and its related genetic variants with hepatocellular carcinoma (HCC) risk and prognosis is not fully understood. Methods We enrolled 100 HCC patients and 8,242 health controls from Sir Run Run Shaw Hospital. Logistic regression model was used to calculate the odds ratio (OR) and 95% CI for HCC risk according to serum 25(OH)D concentration. Mendelian randomization (MR) approach was also conducted to validate the potential causal association of 25(OH)D with HCC risk. Hazard ratio (HR) for the association of SNPs with overall survival and disease-free survival was assessed by multivariate Cox hazard proportional regression model. Results Plasma 25(OH)D level greater than 20 ng/mL increased HCC risk (OR =7.56, 95% CI: 4.58–12.50). MR analysis also showed a slightly increased risk of HCC by 25(OH)D increasing, yet did not reach statistical significance (OR =1.03, 95% CI: 0.31–3.47). With regard to HCC survival, compared to patients with rs8018720 GG genotype, patients with rs8018720 CC/CG genotype had a longer disease-free survival time (HR =0.39, 95% CI: 0.18–0.81). There was an interaction between rs12785878 and 25(OH)D level in continuous scale for HCC mortality. An interaction between rs12785878 and dichotomized 25(OH)D concentration for disease-free survival of HCC patients was also confirmed. Conclusions There is hazard of circulating 25(OH)D concentration for HCC occurrence, but protective effect of the interaction between circulating 25(OH)D concentration and its related genetic variation for HCC prognosis. Further study is needed to confirm or refute these findings in a larger population.
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Affiliation(s)
- Hui Liu
- Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xia Jiang
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Qiaohua Qiao
- Department of Family Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Liying Chen
- Department of Family Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Koichi Matsuda
- Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Guangyi Jiang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tunan Yu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yifan Wang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Hui Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiao Liang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiujun Cai
- Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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25
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Zhang Y, Jiang X, Li X, Găman MA, Kord-Varkaneh H, Rahmani J, Salehi-Sahlabadi A, Day AS, Xu Y. Serum Vitamin D Levels and Risk of Liver Cancer: A Systematic Review and Dose-Response Meta-Analysis of Cohort Studies. Nutr Cancer 2020; 73:1-9. [PMID: 32705896 DOI: 10.1080/01635581.2020.1797127] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Data regarding the relationship between serum vitamin D levels and the risk of liver cancer are conflicting. Therefore, we performed a systematic review and dose-response meta-analysis of all available data of cohort studies on the association of 25-OH-vitamin-D levels with the risk of hepatocellular carcinoma. We conducted a systematic search in PubMed-MEDLINE, Scopus, Cochrane and Web of Science databases for prospective observational studies conducted on the general population from inception to May 2019. Six studies provided data from 6357 participants. According to the pooled HR, the subjects with the highest serum concentrations of vitamin D had a 47% lower risk of liver cancer vs. the subjects with the lowest serum concentrations of vitamin D (pooled HR: 0.53, 95% CI: 0.41-0.68; P < 0.001). There was no significant heterogeneity among the studies (P = 0.431, I2 = 0.0). The pooled HR from the random-effects dose-response model indicated an indirect significant linear association between vitamin D and the risk of liver cancer (coef = -0.017, P < 0.001). However, there was no significant nonlinear dose-response association between serum vitamin D and the risk of liver cancer (coef = -0.0001, P = 0.342). The evidence from this meta-analysis suggests that there may be an inverse relationship between serum vitamin D levels and the risk of liver cancer.
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Affiliation(s)
- Yonggui Zhang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xuefeng Jiang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xiangjun Li
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Science, Jilin University, Changchun, China
| | - Mihnea-Alexandru Găman
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.,Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Hamed Kord-Varkaneh
- Department of Clinical Nutrition and Dietetics, Student Research Committee, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jamal Rahmani
- Department of Clinical Nutrition and Dietetics, Student Research Committee, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ammar Salehi-Sahlabadi
- Department of Clinical Nutrition and Dietetics, Student Research Committee, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Andrew S Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Yan Xu
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China
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26
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Hu MJ, Niu QS, Wu HB, Lu XL, Wang L, Tong XR, Huang F. Association of thyroid cancer risk with plasma 25-hydroxyvitamin D and vitamin D binding protein: a case-control study in China. J Endocrinol Invest 2020; 43:799-808. [PMID: 31863361 DOI: 10.1007/s40618-019-01167-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 12/16/2019] [Indexed: 01/08/2023]
Abstract
PURPOSE To investigate the association of thyroid cancer (TC) with 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (DBP) and examine whether there was an interaction between 25(OH)D and DBP in relation to TC risk. METHODS A matched case-control study based on multiple hospitals included 506 pairs of cases with newly diagnosed TC and controls. All subjects were divided into the quartiles according to the distribution of 25(OH)D and DBP in controls. Odds ratio (OR) and 95% confidence intervals (CIs) for the association of TC with 25(OH)D and DBP were estimated by conditional logistic regression. RESULTS Comparing the highest to lowest quartiles, a decreased TC risk was respectively associated with plasma 25(OH)D (OR 0.63, 95% CI 0.40-1.00, P-trend = 0.046) and DBP (OR 0.49, 95% CI 0.32-0.77, P-trend = 0.001). However, the association between DBP and TC might be modified by 25(OH)D (P-interaction = 0.014) and physical activity (P-interaction = 0.017). Compared to participants with 25(OH)D and DBP concentrations respectively below medians, those with both concentrations above medians had a lower risk of TC (OR 0.56, 95% CI 0.39-0.82). In stratified analysis based on clinical characteristics of tumor, significantly negative association between 25(OH)D, and DBP and TC were observed among the cases with early stage of tumor progression. CONCLUSIONS This study suggested that 25(OH)D and DBP had protective effects against TC. But the negative association between TC and DBP might be modified by 25(OH)D and physical activity.
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Affiliation(s)
- M-J Hu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China
| | - Q-S Niu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China
| | - H-B Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China
| | - X-L Lu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China
| | - L Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China
| | - X-R Tong
- Second Department of Clinical Medicine, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China
| | - Fen Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China.
- Central Laboratory of Preventive Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China.
- Laboratory for Environmental Toxicology, Anhui Medical University, No. 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China.
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27
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Battling IL-17, the troublemaker in alcohol-induced hepatocellular carcinoma. J Hepatol 2020; 72:809-812. [PMID: 32122724 DOI: 10.1016/j.jhep.2020.02.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 02/18/2020] [Accepted: 02/18/2020] [Indexed: 12/04/2022]
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28
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Kozeniecki M, Ludke R, Kerner J, Patterson B. Micronutrients in Liver Disease: Roles, Risk Factors for Deficiency, and Recommendations for Supplementation. Nutr Clin Pract 2019; 35:50-62. [PMID: 31840874 DOI: 10.1002/ncp.10451] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Micronutrients are essential components of the diet and are required to maintain fundamental bodily functions. Liver disease has a profound effect on nutrient intake, metabolism of nutrients, and nutrition status, often resulting in some degree of malnutrition, including micronutrient deficiency. Vitamin and mineral deficiencies can impair metabolic processes at the cellular and biochemical level even before clinical and physical alterations are seen. It is essential that micronutrient status is evaluated as part of a comprehensive nutrition assessment for all patients with chronic or advanced liver disease. Early intervention to correct suspected or confirmed deficiencies may minimize symptoms and improve clinical outcomes and quality of life. In this narrative review, different types of liver disease and associated micronutrient abnormalities are outlined, and methods of micronutrient assessment and supplementation are discussed.
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Affiliation(s)
- Michelle Kozeniecki
- Department of Nutrition Services, Froedtert Hospital, Milwaukee, Wisconsin, USA
| | - Rachel Ludke
- Department of Nutrition Services, Froedtert Hospital, Milwaukee, Wisconsin, USA
| | - Jennifer Kerner
- Transplant Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Brittney Patterson
- Clinical Nutrition Department, Stanford Health Care, Stanford, California, USA
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A Review of the Potential Benefits of Increasing Vitamin D Status in Mongolian Adults through Food Fortification and Vitamin D Supplementation. Nutrients 2019; 11:nu11102452. [PMID: 31615079 PMCID: PMC6835745 DOI: 10.3390/nu11102452] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 10/02/2019] [Accepted: 10/07/2019] [Indexed: 02/06/2023] Open
Abstract
Serum 25-hydroxyvitamin D (25(OH)D) concentrations are low in Mongolia, averaging 22 ng/mL in summer and only 8 ng/mL in winter. Mongolians have high incidence and/or prevalence of several diseases linked to low 25(OH)D concentrations, including ischemic heart disease, malignant neoplasms, cirrhosis of the liver, ischemic stroke, lower respiratory tract infections, preterm birth complications, and diabetes mellitus. Fortifying regularly consumed foods such as flour, milk, and edible oils with vitamin D3 could raise 25(OH)D concentrations by about 10 ng/mL. However, to achieve 25(OH)D concentrations of 30–40 ng/mL in adults, vitamin D intakes of 1000 to 4000 IU/day would be required, making personal supplement use necessary. On the basis of prospective observational studies and clinical trials of disease incidence or known mortality rates and adverse pregnancy and birth outcomes, raising mean serum 25(OH)D concentrations to 40 ng/mL would likely reduce incidence and mortality rates for those and other diseases, reduce the rate of adverse pregnancy and birth outcomes, and increase mean life expectancy by one year or more.
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Han J, Guo X, Yu X, Liu S, Cui X, Zhang B, Liang H. 25-Hydroxyvitamin D and Total Cancer Incidence and Mortality: A Meta-Analysis of Prospective Cohort Studies. Nutrients 2019; 11:nu11102295. [PMID: 31561503 PMCID: PMC6835972 DOI: 10.3390/nu11102295] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 09/18/2019] [Accepted: 09/20/2019] [Indexed: 12/24/2022] Open
Abstract
Epidemiological studies have suggested inconclusive associations between 25-hydroxyvitamin D and total cancer incidence and mortality. The aim of this study was to quantitatively assess these associations by combining results from prospective cohort studies. A systematic literature search was implemented in PubMed and Scopus databases in April 2019. Comparing the highest with the lowest categories, the multivariate-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using a random-effects model. A trend estimation was performed using a two-stage, dose-response, meta-analysis method. Twenty-three independent prospective studies were included for data synthesis. Eight studies investigated the association between 25-hydroxyvitamin D and the risk of cancer incidence (7511 events and 70,018 participants), and the summary estimate showed that 25-hydroxyvitamin D is marginally associated with cancer risk (Summary RR = 0.86; 95% CI: 0.73, 1.02; I2 = 70.8%; p = 0.001). Sixteen studies investigated the association between 25-hydroxyvitamin D and the risk of cancer mortality (8729 events and 101,794 participants), and a higher 25-hydroxyvitamin D concentration was inversely associated with the risk of cancer mortality (Summary RR = 0.81; 95% CI: 0.71, 0.93; I2 = 48.8%, p = 0.012). Dose-response analysis indicated that the risk of cancer incidence was reduced by 7% (RRs = 0.93; 95% CI: 0.91, 0.96), and the risk of cancer mortality was reduced by 2% (RRs = 0.98; 95% CI: 0.97, 0.99), with each 20 nmol/L increment of 25-hydroxyvitamin D concentration. This meta-analysis provides evidence that a higher 25-hydroxyvitamin D concentration is associated with a lower cancer incidence and cancer mortality.
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Affiliation(s)
- Jianmin Han
- Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China.
| | - Xiaofei Guo
- Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China.
| | - Xiao Yu
- Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China.
| | - Shuang Liu
- Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China.
| | - Xinyue Cui
- Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China.
| | - Bo Zhang
- Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China.
| | - Hui Liang
- Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China.
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Serum folate concentrations at diagnosis are associated with hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort study. Br J Nutr 2019; 121:1376-1388. [DOI: 10.1017/s0007114519000734] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AbstractExisting data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
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Wu YQ, Fan WZ, Xue M, Guo J, Wei JL, Wang Y, Yao W, Zhao Y, Li JP. 25-OH-vitamin D deficiency identifies poor tumor response in hepatocellular carcinoma treated with transarterial chemoembolization. Clin Transl Oncol 2019; 22:70-80. [PMID: 31183764 DOI: 10.1007/s12094-019-02146-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 04/08/2019] [Indexed: 01/25/2023]
Abstract
PURPOSE Vitamin D is implicated linked to liver cancer and chronic liver diseases, but its association with tumor response in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) remains unclear. This study aimed to determine whether vitamin D levels influence tumor response in HCC patients treated with TACE. METHODS A total of 58 HCC patients undergoing TACE were enrolled in the study. Serum 25-hydroxyvitamin D (25-OHD) levels were determined at baseline and 1 day after TACE using electrochemiluminescence immunoassay. Response to TACE was evaluated after a 4-6 week interval. Univariate and multivariate analyses with Cox regression model were performed to determine the risk factors associated with tumor response. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of baseline 25-OHD levels on tumor response in HCC patients undergoing TACE. RESULTS 43.1% of HCC patients showed 25-OHD deficiency. Baseline 25-OHD level was associated with liver cirrhosis (P = 0.025), vascular invasion (P = 0.031), Barcelona Clinic Liver Cancer stage (P = 0.002) and an alanine aminotransferase increase after TACE (P = 0.021). Serum 25-OHD level was significantly decreased 1 day after TACE (P = 0.045). Multiple tumor numbers (P = 0.034) and low baseline 25-OHD levels (P = 0.040) were independently correlated with poor tumor response after TACE. ROC curve analysis showed that baseline 25-OHD levels present better predictive performance for OR in those patients, compared with other current clinical test pointers. CONCLUSION Our study suggested that 25-OHD deficiency at baseline is a prognostic indicator for a poor tumor response in hepatocellular carcinoma treated with TACE.
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Affiliation(s)
- Y-Q Wu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - W-Z Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - M Xue
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - J Guo
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - J-L Wei
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - Y Wang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - W Yao
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - Y Zhao
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China
| | - J-P Li
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China.
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Vitamin D3 from Ultraviolet-B Exposure or Oral Intake in Relation to Cancer Incidence and Mortality. Curr Nutr Rep 2019; 8:203-211. [DOI: 10.1007/s13668-019-0262-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Goyal H, Perisetti A, Rahman MR, Levin A, Lippi G. Vitamin D and Gastrointestinal Cancers: A Narrative Review. Dig Dis Sci 2019; 64:1098-1109. [PMID: 30511197 DOI: 10.1007/s10620-018-5400-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 11/27/2018] [Indexed: 12/14/2022]
Abstract
Calcitriol (1,25(OH)2D3) performs various activities throughout the body. Although low serum 25-hydroxyvitamin D [25(OH)D] levels are associated with several disease processes such as risk of fractures and falls, hypertension, cardiovascular disease, and diabetes mellitus, recent evidence attests that this important hormone also regulates several cellular pathways involved in cancer development and progression. Calcitriol modulates several genes controlling gut physiology and calcium homeostasis and also maintains the integrity of epithelial barriers, regulates the absorption of phosphate and calcium, and modulates host defense against pathogens and inflammatory response by interplaying with several types of secretory and immune cells. Vitamin D deficiency is significantly related to increased risk of developing certain types of cancer. This deficiency can be prevented by vitamin D supplementation which is both economical and safe. This can lower the risk of developing cancer and also improve the prognosis of patients with gastrointestinal malignancy, but epidemiological data remain inconsistent. Several retrospective observational studies have demonstrated the benefits of vitamin D supplementation, but a few randomized controlled trials have not seemingly supported the beneficial role of vitamin D supplementation in gastrointestinal cancers. Therefore, in this literature review, we aimed to examine the possible role of vitamin D in gastrointestinal malignancies, including gastric, esophageal, pancreatic, hepatic, and colorectal cancers.
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Affiliation(s)
- Hemant Goyal
- Mercer University School of Medicine, 707 Pine St, Macon, GA, 31201, USA.
| | - Abhilash Perisetti
- University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
| | - M Rubayat Rahman
- University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR, 72205, USA
| | - Avi Levin
- Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
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35
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Matsuda A, Ishiguro K, Yan IK, Patel T. Therapeutic Efficacy of Vitamin D in Experimental c-MET-β-Catenin-Driven Hepatocellular Cancer. Gene Expr 2019; 19:151-159. [PMID: 30157994 PMCID: PMC6466179 DOI: 10.3727/105221618x15355518848281] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Aberrant activation of β-catenin signaling is frequently observed in hepatocellular cancer. Although Wnt/β-catenin signaling can be targeted by vitamin D, therapeutic use of vitamin D for this purpose is not currently established. We evaluated the therapeutic use of vitamin D or its analogs using a synthetic transgenic mouse of hepatocarcinogenesis induced by mutant β-catenin, and MET overexpression in which 75% of mice develop well-differentiated HCC within 8 weeks in the absence of fibrosis. Vitamin D receptor expression was similar in both tumoral and nontumoral tissue. There was no significant difference in overall survival, or in tumor progression assessed by imaging, biochemical, or tumor cell burden assessments in mice receiving a vitamin D-supplemented diet containing 12.0 IU VD/g (HVD) compared with a standard diet (SD) containing 2.3 IU VD/g. Furthermore, systemic treatment with calcitriol [vitamin D analog 1α,25(OH)₂D₃] or EB1089 (synthetic vitamin D analog) by intraperitoneal injection for 4 weeks prolonged median survival but did not increase overall survival compared with controls. Although tumor formation was delayed in males compared with that in females, there was no difference in overall survival between males and females. In conclusion, although 1α,25(OH)₂D₃ is reported to inhibit β-catenin signaling, as well as proliferation, migration, and differentiation in cancer cells, neither dietary supplementation with vitamin D nor treatment with vitamin D analogs altered the formation or growth of HCC associated with β-catenin activation. These results conclusively demonstrate the lack of utility of targeting vitamin D for therapy of HCC in this setting.
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Affiliation(s)
- Akiko Matsuda
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | - Kaori Ishiguro
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | - Irene K. Yan
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | - Tushar Patel
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
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Buonomo AR, Scotto R, Zappulo E, Nerilli M, Pinchera B, Perruolo G, Formisano P, Nappa S, Gentile I. Severe Vitamin D Deficiency Increases Mortality Among Patients With Liver Cirrhosis Regardless of the Presence of HCC. In Vivo 2019; 33:177-182. [PMID: 30587620 DOI: 10.21873/invivo.11456] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 10/08/2018] [Accepted: 10/12/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study was to investigate the association between vitamin D deficiency (<10 mg/ml) and mortality in patients with and without hepatocellular carcinoma (HCC) in a cohort of patients with liver cirrhosis. MATERIALS AND METHODS A prospective study was conducted among 345 patients with liver cirrhosis. RESULTS At enrolment, 46 (13.3%) patients had HCC. Severe vitamin D deficiency was associated with mortality (p<0.01). At the survival analysis, alpha-fetoprotein >10 ng/ml (p=0.003), vitamin D deficiency (p<0.001), a Model for End-Stage Liver Disease score ≥15 (p<0.001), Child-Pugh class B and C (versus A) (p<0.001) and the presence of active HCC (p<0.001) were strongly associated with death. At the multivariate Cox regression analysis, only Child-Pugh class B and C (versus A) and vitamin D deficiency were found to be significantly associated with death during the follow-up period (p<0.001 and p=0.006, respectively). CONCLUSION Vitamin D deficiency is common in patients with HCC, it is associated with active HCC and it negatively affects the overall survival of patients with cirrhosis.
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Affiliation(s)
- Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, Federico II University of Naples, Naples, Italy
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, Federico II University of Naples, Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, Federico II University of Naples, Naples, Italy
| | - Mariagiovanna Nerilli
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, Federico II University of Naples, Naples, Italy
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, Federico II University of Naples, Naples, Italy
| | - Giuseppe Perruolo
- Department of Medical Translational Sciences, Federico II University of Naples, Naples, Italy
| | - Pietro Formisano
- Department of Medical Translational Sciences, Federico II University of Naples, Naples, Italy
| | - Salvatore Nappa
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, Federico II University of Naples, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, Federico II University of Naples, Naples, Italy
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Abstract
Vitamin D, traditionally well known for its role in maintaining optimal health through its contribution to calcium metabolism and skeletal health, has received increased attention over the past two decades, with considerable focus being placed on its nonskeletal benefits. This paper is a narrative review of the nonskeletal health benefits of vitamin D, of particular interest to inhabitants of Mediterranean countries, namely, autism, cancer, cardiovascular disease, chronic obstructive pulmonary disease, dental caries, diabetes mellitus, erectile dysfunction, hypertension, metabolic syndrome, respiratory tract infections, all-cause mortality, and pregnancy and birth outcomes, because of the relatively high incidence and/or prevalence of these disorders in this region. Currently, the best evidence is coming out of observational studies related to serum 25-hydroxyvitamin D [25(OH)D] concentrations. Vitamin D clinical trials have generally been poorly designed and conducted, usually being based on vitamin D dose rather than 25(OH)D concentration. The optimal 25(OH)D concentration is above 75 nmol/l (30 ng/ml), with even better health outcomes in the range of 100-150 nmol/l. Achieving these concentrations with vitamin D3 supplements will require 1000-4000 IU/day of vitamin D3. Sensible sun exposure should also be encouraged. Countries should also consider fortifying grain and dairy products with vitamin D3.
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Affiliation(s)
- William B Grant
- Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA, 94164-1603, USA.
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VoPham T. Environmental risk factors for liver cancer and nonalcoholic fatty liver disease. CURR EPIDEMIOL REP 2019; 6:50-66. [PMID: 31080703 DOI: 10.1007/s40471-019-0183-2] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Purpose of review The objective of this review was to summarize recent epidemiologic research examining the associations between environmental exposures and liver cancer and nonalcoholic fatty liver disease (NAFLD). Recent findings There were 28 liver cancer studies showing positive associations for exposures to aflatoxin, air pollution, polycyclic aromatic hydrocarbons, asbestos, chimney sweeping occupation, and paints; an inverse association for ultraviolet radiation; and null/inconsistent results for organic solvents, pesticides, perfluorooctanoic acid, nuclear radiation, iron foundry occupation, and brick kiln pollution. There were n=5 NAFLD studies showing positive associations for heavy metals, methyl tertiary-butyl ether, and selenium; and no association with trihalomethanes. Summary Evidence suggests that particular environmental exposures may be associated with liver cancer and NAFLD. Future liver cancer studies should examine specific histological subtypes and assess historical environmental exposures. Future NAFLD research should examine incident, biopsy-confirmed cases and the potential role of obesity and/or diabetes in studies of environmental factors and NAFLD.
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Affiliation(s)
- Trang VoPham
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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Ferrándiz-Pulido C, Torres IB, Juárez-Dobjanschi C, Zarzoso-Muñoz I, Berastegui C, Castells L, García-Patos V, Moreso F. Vitamin D deficiency in solid-organ transplant recipients from a Spanish Mediterranean population. Clin Exp Dermatol 2019; 44:e103-e109. [PMID: 30701578 DOI: 10.1111/ced.13915] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/10/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND Solid-organ transplant recipients (SOTRs) are at risk of developing vitamin D deficiency, mainly caused by reduced sunlight exposure with subsequent low vitamin D synthesis in the skin. AIM To analyse whether SOTRs from a Spanish Mediterranean region were vitamin D-deficient. METHODS This was a cross-sectional, descriptive and observational study in a transplantation-specialized Dermatological Unit from a Mediterranean area to determine the calcidiol levels of a cohort of 78 consecutively attending patients not receiving vitamin D supplements. Serum 25(OH)D3 levels were determined and clinical characteristics were collected. Logistic regression analysis was used to analyse variables associated with dichotomized 25(OH)D3 levels (≤ or > 10 ng/mL). RESULTS The cohort comprised 30 lung, 29 kidney and 19 liver transplant recipients. Mean calcidiol was 18 ± 9 ng/mL. Deficiency of 25(OH)D3 was present in 19% of patients, while 68% had insufficient levels and 13% had sufficient levels. Following multivariate logistic regression analysis, the season of blood sampling remained the only predictor of deficient 25(OH)D3 levels. CONCLUSION Despite living in a mid-latitude country with sunny weather, our SOTR population was at high risk of developing hypovitaminosis D, especially in autumn/winter. Avoiding sun exposure is important to prevent skin cancer, but careful monitoring of vitamin D status is recommended, with supplementation if hypovitaminosis D is detected.
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Affiliation(s)
- C Ferrándiz-Pulido
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - I B Torres
- Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - C Juárez-Dobjanschi
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - I Zarzoso-Muñoz
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - C Berastegui
- Department of Pneumology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - L Castells
- Department of Internal Medicine-Hepatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - V García-Patos
- Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - F Moreso
- Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
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40
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Vitamin D Receptor Fok I Polymorphism and Risk of Hepatocellular Carcinoma in HBV-Infected Patients. HEPATITIS MONTHLY 2019. [DOI: 10.5812/hepatmon.85075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Fang AP, Chen PY, Wang XY, Liu ZY, Zhang DM, Luo Y, Liao GC, Long JA, Zhong RH, Zhou ZG, Xu YJ, Xu XJ, Ling WH, Chen MS, Zhang YJ, Zhu HL. Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort. Int J Cancer 2019; 144:2823-2832. [PMID: 30426509 DOI: 10.1002/ijc.31991] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/19/2018] [Accepted: 11/06/2018] [Indexed: 12/23/2022]
Abstract
Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22-2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36-3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89-1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99-2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.
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Affiliation(s)
- Ai-Ping Fang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
| | - Pei-Yan Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Yan Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zhao-Yan Liu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Dao-Ming Zhang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yun Luo
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Gong-Cheng Liao
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Jing-An Long
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Rong-Huan Zhong
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zhong-Guo Zhou
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Yan-Jun Xu
- Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
| | - Xiao-Jun Xu
- Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
| | - Wen-Hua Ling
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
| | - Min-Shan Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Yao-Jun Zhang
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Hui-Lian Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
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Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn) 2018; 22:141-150. [PMID: 30455585 PMCID: PMC6238087 DOI: 10.5114/wo.2018.78941] [Citation(s) in RCA: 148] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 08/25/2018] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver responsible for an increasing number of cancer-related deaths, especially in developing economies of Asia and Africa. A plethora of risk factors have been described in the literature. Some of the important ones include chronic viral hepatitis, liver cirrhosis, environmental toxins such as aflatoxin, non-alcoholic fatty liver disease, lifestyle factors like alcohol consumption, smoking, and dietary factors, metabolic diseases like diabetes mellitus and obesity, and genetic and hereditary disorders. The development of HCC is complex involving sustained inflammatory damage leading to hepatocyte necrosis, regeneration, and fibrotic deposition. It also poses multiple challenges in diagnosis and treatment despite advances in diagnostic, surgical, and other therapeutic advancements. This is a narrative review of findings of multiple studies that were retrieved from electronic databases like PubMed, MEDLINE, Embase, Google Scholar, Scopus, and Cochrane. We summarise the current knowledge regarding the epidemiology and various risk factors for the development of HCC with a brief note on various prevention strategies.
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Athuluri-Divakar SK, Hoshida Y. Generic chemoprevention of hepatocellular carcinoma. Ann N Y Acad Sci 2018; 1440:23-35. [PMID: 30221358 DOI: 10.1111/nyas.13971] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 08/21/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023]
Abstract
Chronic fibrotic liver disease caused by viral or metabolic etiologies is a high-risk condition for developing hepatocellular carcinoma (HCC). Even after curative treatment of early-stage HCC tumor, the carcinogenic microenvironment persists in the remnant diseased liver and supports the development of de novo HCC tumors (de novo HCC recurrence). Therefore, prevention of HCC development in patients at risk of not only first-primary but also second-primary HCC tumors is theoretically the most impactful strategy to improve patient prognosis. However, no such therapy has been established to date. One major challenge is the identification of clinically relevant targets that can be achieved by utilizing the reverse-engineering strategy of chemoprevention discovery, which integrates omics information from clinical cohorts with completed follow-up for cancer development. Clinical and experimental studies have suggested etiology-specific and generic candidate HCC chemoprevention strategies, including statins, antidiabetic drugs, selective molecular targeted agents, and dietary and nutritional substances. Clinical testing of the candidate compounds can be cost-effectively performed by combining it with HCC risk biomarker evaluation to specify the target patient population most likely to benefit from the therapy. Nontoxic, generic agents will have broad clinical applicability across the diverse HCC etiologies and clinical contexts and are expected to substantially improve the still dismal prognosis of HCC.
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Affiliation(s)
- Sai Krishna Athuluri-Divakar
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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44
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R Ebrahim A, El-Mesery M, El-Karef A, Eissa LA. Vitamin D potentiates anti-tumor activity of 5-fluorouracil via modulating caspase-3 and TGF-β1 expression in hepatocellular carcinoma-induced in rats. Can J Physiol Pharmacol 2018; 96:1218-1225. [PMID: 30205014 DOI: 10.1139/cjpp-2018-0445] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
We investigated the role of vitamin D (Vit D) alone and in combination with 5-fluorouracil (5-FU) in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) in rats. Fifty male Sprague-Dawley rats were randomized into a control group and 4 groups that received TAA (200 mg/kg, i.p.) twice per week for 16 weeks. These 4 groups were further divided as follows: HCC group; 5-FU group (75 mg/kg, i.p., once weekly for 3 weeks starting from the 12th week); Vit D group (200 IU/kg daily by oral tube for 16 weeks); and 5-FU + Vit D group (received the previously mentioned dosage regimens of 5-FU and Vit D). HCC was detected by histopathological changes in liver sections and the elevation of serum α-fetoprotein (AFP). Treatment with 5-FU + Vit D significantly decreased gene expression of nuclear factor erythroid 2-related factor 2 (NrF2) and transforming growth factor β1 (TGF-β1) at both the gene and protein level and serum AFP concentrations in comparison with their corresponding monotherapy. Moreover, 5-FU + Vit D treatment enhanced apoptosis by increasing caspase-3 gene and protein expression. Conclusively, Vit D enhances antitumor activity of 5-FU in an HCC-induced model and improves liver function of treated animals. Combination therapy in a TAA-induced HCC rat model was more effective than 5-FU or Vit D through the modulation of TGF-β1, caspase-3, and NrF2 expressions.
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Affiliation(s)
- Amal R Ebrahim
- a Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| | - Mohamed El-Mesery
- a Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| | - Amro El-Karef
- b Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt
| | - Laila A Eissa
- a Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
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45
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Lai GY, Wang JB, Weinstein SJ, Parisi D, Horst RL, McGlynn KA, Männistö S, Albanes D, Freedman ND. Association of 25-Hydroxyvitamin D with Liver Cancer Incidence and Chronic Liver Disease Mortality in Finnish Male Smokers of the ATBC Study. Cancer Epidemiol Biomarkers Prev 2018; 27:1075-1082. [PMID: 29720370 PMCID: PMC6148352 DOI: 10.1158/1055-9965.epi-17-0877] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 12/19/2017] [Accepted: 04/27/2018] [Indexed: 01/23/2023] Open
Abstract
Background: Although circulating 25-hydroxyvitamin D [25(OH)D] concentrations were linked to liver cancer and chronic liver disease (CLD) in laboratory studies, few epidemiologic studies have addressed the associations.Methods: Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, we measured 25(OH)D in baseline serum of 202 incident liver cancer cases and 225 CLD deaths that occurred during nearly 25 years of follow-up, and 427 controls. ORs and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. We examined predetermined clinically defined cut-points, and season-specific and season-standardized quartiles.Results: Low serum 25(OH)D concentrations were associated with higher risk of liver cancer (<25 nmol/L vs. ≥50 nmol/L: 1.98; 95% CI, 1.22-3.20; Ptrend across categories = 0.003) and CLD mortality (1.93; 95% CI, 1.23-3.03; Ptrend = 0.006) in models adjusted for age and date of blood draw. After additional adjustment for body mass index, diabetes, smoking, and other potential confounders, the association remained statistically significant for liver cancer (1.91; 95% CI, 1.16-3.15; Ptrend = 0.008), but was somewhat attenuated for CLD mortality (1.67; 95% CI, 1.02-2.75; Ptrend = 0.05). Associations were similar for analyses using season-specific and season-standardized quartiles, and after excluding participants with diabetes, or hepatitis B or C.Conclusions: Our results suggest a possible preventive role for vitamin D against liver cancer and CLD, although the importance of the liver for vitamin D metabolism and the lack of information about underlying liver disease makes reverse causality a concern.Impact: Future studies are needed to evaluate associations of vitamin D with liver cancer and liver disease in other populations, particularly those with a different constellation of risk factors. Cancer Epidemiol Biomarkers Prev; 27(9); 1075-82. ©2018 AACR.
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Affiliation(s)
- Gabriel Y Lai
- Environmental Epidemiology Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.
| | - Jian-Bing Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, China
| | - Stephanie J Weinstein
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | | | | | - Katherine A McGlynn
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Satu Männistö
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
| | - Demetrius Albanes
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Neal D Freedman
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
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46
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VoPham T, Bertrand KA, Tamimi RM, Laden F, Hart JE. Ambient PM 2.5 air pollution exposure and hepatocellular carcinoma incidence in the United States. Cancer Causes Control 2018; 29:563-572. [PMID: 29696510 PMCID: PMC5940508 DOI: 10.1007/s10552-018-1036-x] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 04/18/2018] [Indexed: 12/15/2022]
Abstract
PURPOSE To conduct the first epidemiologic study prospectively examining the association between particulate matter air pollution < 2.5 µm in diameter (PM2.5) exposure and hepatocellular carcinoma (HCC) risk in the U.S. METHODS Surveillance, Epidemiology, and End Results (SEER) provided information on HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries across the U.S. Ambient PM2.5 exposure was estimated by linking the SEER county with a spatial PM2.5 model using a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios and 95% confidence intervals (CIs) for the association between ambient PM2.5 exposure per 10 µg/m3 increase and HCC risk adjusting for individual-level age at diagnosis, sex, race, year of diagnosis, SEER registry, and county-level information on health conditions, lifestyle, demographic, socioeconomic, and environmental factors. RESULTS Higher levels of ambient PM2.5 exposure were associated with a statistically significant increased risk for HCC (n = 56,245 cases; adjusted IRR per 10 µg/m3 increase = 1.26, 95% CI 1.08, 1.47; p < 0.01). CONCLUSIONS If confirmed in studies with individual-level PM2.5 exposure and risk factor information, these results suggest that ambient PM2.5 exposure may be a risk factor for HCC in the U.S.
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Affiliation(s)
- Trang VoPham
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.
| | - Kimberly A Bertrand
- Slone Epidemiology Center at Boston University, 72 East Concord Street, Boston, MA, 02118, USA
| | - Rulla M Tamimi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA
| | - Francine Laden
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA
- Exposure, Epidemiology and Risk Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA
| | - Jaime E Hart
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA
- Exposure, Epidemiology and Risk Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA
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47
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Mak LY, Cruz-Ramón V, Chinchilla-López P, Torres HA, LoConte NK, Rice JP, Foxhall LE, Sturgis EM, Merrill JK, Bailey HH, Méndez-Sánchez N, Yuen MF, Hwang JP. Global Epidemiology, Prevention, and Management of Hepatocellular Carcinoma. Am Soc Clin Oncol Educ Book 2018; 38:262-279. [PMID: 30231359 DOI: 10.1200/edbk_200939] [Citation(s) in RCA: 145] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
The incidence rate of hepatocellular carcinoma (HCC) is rising. It is one of the most common cancers worldwide and accounts for substantial morbidity and mortality. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, and nonalcoholic fatty liver disease (NAFLD) are the most important etiologies of HCC, and effective screening and management strategies are crucial to reduce the HCC risk. For HBV, which accounts for the majority of HCC cases, most infections were acquired via perinatal and early horizontal transmission. Universal vaccination of newborns has led to a decline in HCC incidence compared with the pre-vaccination era. Effective antiviral therapies with nucleos(t)ide analogues or pegylated interferon reduced the incidence of HCC. For HCV, the emergence of effective direct-acting antiviral (DAA) agents has substantially improved cure rates; therefore all patients with HCV should be considered for DAA treatment. The most important obstacle in eliminating HCV is access to therapy. For NAFLD, the global incidence is increasing rapidly, thus its impact on HCC incidence may be explosive. Progression to HCC in NAFLD happens particularly in those with nonalcoholic steatohepatitis (NASH) and exacerbated by metabolic syndrome, or PNPLA3 gene polymorphism. Lifestyle changes are imperative while drug therapy has yet to demonstrate substantive protective effects on HCC prevention. For management of HCC, early diagnosis via imaging surveillance among persons with HCC risk factors remains the most important strategy to identify early-stage disease appropriate for resection or transplantation.
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MESH Headings
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/prevention & control
- Carcinoma, Hepatocellular/therapy
- Disease Management
- Global Health
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/therapy
- Hepatitis B, Chronic/virology
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/therapy
- Hepatitis C, Chronic/virology
- Humans
- Incidence
- Liver Neoplasms/diagnosis
- Liver Neoplasms/epidemiology
- Liver Neoplasms/prevention & control
- Liver Neoplasms/therapy
- Non-alcoholic Fatty Liver Disease/complications
- Non-alcoholic Fatty Liver Disease/diagnosis
- Non-alcoholic Fatty Liver Disease/therapy
- Population Surveillance
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Affiliation(s)
- Lung-Yi Mak
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Vania Cruz-Ramón
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Paulina Chinchilla-López
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Harrys A Torres
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Noelle K LoConte
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - John P Rice
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Lewis E Foxhall
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Erich M Sturgis
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Janette K Merrill
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Howard H Bailey
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Nahum Méndez-Sánchez
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Man-Fung Yuen
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
| | - Jessica P Hwang
- From the Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China; Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; University of Wisconsin School of Medicine, Madison, WI; American Society of Clinical Oncology, Alexandria, VA
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VoPham T, Weaver MD, Vetter C, Hart JE, Tamimi RM, Laden F, Bertrand KA. Circadian Misalignment and Hepatocellular Carcinoma Incidence in the United States. Cancer Epidemiol Biomarkers Prev 2018; 27:719-727. [PMID: 29636342 DOI: 10.1158/1055-9965.epi-17-1052] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 01/31/2018] [Accepted: 04/05/2018] [Indexed: 12/29/2022] Open
Abstract
Background: Circadian misalignment may increase the risk of developing hepatocellular carcinoma (HCC). The aim of this study was to examine the association between distance from time zone meridian, a proxy for circadian misalignment, and HCC risk in the United States adjusting for known HCC risk factors.Methods: Surveillance, Epidemiology, and End Results (SEER) provided information on 56,347 HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries in the United States. Distance from time zone meridian was estimated using the location of each SEER county's Center of Population in a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between distance from time zone meridian and HCC risk adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level prevalence of health conditions, lifestyle factors, shift work occupation, socioeconomic status, and demographic and environmental factors.Results: A 5-degree increase in longitude moving east to west within a time zone was associated with a statistically significant increased risk for HCC (IRR, 1.07; 95% CI, 1.01-1.14, P = 0.03). A statistically significant positive association was observed among those <65 years old, while no association was observed among individuals ≥65 years old (Pfor interaction < 0.01).Conclusions: Circadian misalignment from residing in the western region of a time zone may impact hepatocarcinogenesis.Impact: Circadian misalignment may be an independent risk factor for HCC. Cancer Epidemiol Biomarkers Prev; 27(7); 719-27. ©2018 AACR.
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Affiliation(s)
- Trang VoPham
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. .,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Matthew D Weaver
- Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts.,Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts
| | - Céline Vetter
- Department of Integrative Physiology, University of Colorado, Boulder, Boulder, Colorado.,Broad Institute of Harvard and MIT, Cambridge, Massachusetts
| | - Jaime E Hart
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Rulla M Tamimi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Francine Laden
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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49
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Raoul JL, Raimbourg J, Hiret S, Adhoute X, Senellart H. [Hepatocellular carcinoma: Increase in incidence or future plague?]. Bull Cancer 2018; 105:502-507. [PMID: 29567280 DOI: 10.1016/j.bulcan.2018.02.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 02/05/2018] [Accepted: 02/06/2018] [Indexed: 12/19/2022]
Abstract
Hepatocellular carcinoma is the third most frequent cause of cancer death worldwide, particularly in Asia and Africa. Most cases complicate an underlying liver cirrhosis due to hepatitis B or C chronic virus infection or alcoholic abuse. But, following the current epidemics of obesity and type 2 diabetes, it appears that these diseases, associated in metabolic syndrome, are responsible for non alcoholic fatty liver disease at risk of HCC frequently before the stage of cirrhosis. Recent hypotheses consider that in the near future, cancer deaths due to HCC will overpass in USA those due to breast or colorectal cancers. Governments should develop policies to prevent obesity, type 2 diabetes and the metabolic syndrome as well as fight against alcoholism and hepatitis B and C virus infections.
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Affiliation(s)
- Jean-Luc Raoul
- Institut de cancérologie de l'Ouest, département d'oncologie médicale, site de Nantes, boulevard J.-Monod, 44805 Saint-Herblain cedex, France.
| | - Judith Raimbourg
- Institut de cancérologie de l'Ouest, département d'oncologie médicale, site de Nantes, boulevard J.-Monod, 44805 Saint-Herblain cedex, France
| | - Sandrine Hiret
- Institut de cancérologie de l'Ouest, département d'oncologie médicale, site de Nantes, boulevard J.-Monod, 44805 Saint-Herblain cedex, France
| | - Xavier Adhoute
- Hôpital Saint-Joseph, département d'hépato-gastroentérologie, 26, boulevard de Louvain, 13008 Marseille, France
| | - Hélène Senellart
- Institut de cancérologie de l'Ouest, département d'oncologie médicale, site de Nantes, boulevard J.-Monod, 44805 Saint-Herblain cedex, France
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50
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Budhathoki S, Hidaka A, Yamaji T, Sawada N, Tanaka-Mizuno S, Kuchiba A, Charvat H, Goto A, Kojima S, Sudo N, Shimazu T, Sasazuki S, Inoue M, Tsugane S, Iwasaki M. Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. BMJ 2018; 360:k671. [PMID: 29514781 PMCID: PMC5838719 DOI: 10.1136/bmj.k671] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. DESIGN Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. SETTING Nine public health centre areas across Japan. PARTICIPANTS 3301 incident cases of cancer and 4044 randomly selected subcohort participants. EXPOSURE Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. MAIN OUTCOME MEASURE Incidence of overall or site specific cancer. RESULTS Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. CONCLUSIONS In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites.
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Affiliation(s)
- Sanjeev Budhathoki
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Akihisa Hidaka
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Taiki Yamaji
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Norie Sawada
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Sachiko Tanaka-Mizuno
- Department of Medical Statistics, Shiga University of Medical Science, Ohtsu, Shiga, 520-2192, Japan
| | - Aya Kuchiba
- Division of Biostatistical Research, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
- Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Hadrien Charvat
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Atsushi Goto
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Satoshi Kojima
- CL New Product Development Department, Fujirebio Inc., Hachioji-shi, Tokyo, 192-0031, Japan
| | - Natsuki Sudo
- CL New Product Development Department, Fujirebio Inc., Hachioji-shi, Tokyo, 192-0031, Japan
| | - Taichi Shimazu
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shizuka Sasazuki
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Manami Inoue
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
| | - Motoki Iwasaki
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan
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