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Pan J, Liu R, Lu W, Peng H, Yang J, Zhang Q, Yu T, Huo B, Wei X, Liang H, Zhou L, Sun Y, Hu Y, Wen S, Fu J, Chiao PJ, Xia X, Liu J, Huang P. SQLE-catalyzed squalene metabolism promotes mitochondrial biogenesis and tumor development in K-ras-driven cancer. Cancer Lett 2025; 616:217586. [PMID: 40015662 DOI: 10.1016/j.canlet.2025.217586] [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] [Received: 12/03/2024] [Revised: 02/13/2025] [Accepted: 02/22/2025] [Indexed: 03/01/2025]
Abstract
It is well known that activation of oncogenic K-ras alone is insufficient to drive tumor development and that additional factors are needed for full malignant transformation, but the metabolic pathways and regulatory mechanisms that facilitate K-ras-driven cancer development remain to be characterized. Here we show that SQLE, a key enzyme in cholesterol synthesis, is upregulated in K-ras-driven cancer and its high expression is correlated with poor clinical outcome. K-ras regulates SQLE expression in a biphasic manner through reactive oxygen species and MYC signaling. Surprisingly, the pro-oncogenic role of SQLE is not mediated by promoting cholesterol synthesis, but by metabolic removal of squalene and thus mitigating its suppressive effect on the PGC-1α-mediated mitochondrial biogenesis and metabolism. Genetic silencing of SQLE in pancreatic cancer cells causes an accumulation of cellular squalene, which binds to Sp1 protein and causes a formation of a tight Sp1-TFAP2E promoter DNA complex with a highly negative binding score. This aberrant squalene/Sp1/TFAP2E promoter complex hinders the expression of TFAP2E and its downstream molecule PGC-1α, leading to suppression of mitochondrial metabolism and an almost complete inhibition of tumor formation in vivo. Importantly, administration of pharmacological squalene to mice bearing pancreatic cancer xenografts could significantly inhibit tumor growth. Our study has revealed a previously unrecognized role of SQLE in regulating gene expression and mitochondrial metabolism to facilitate K-ras-driven cancer development, and identified SQLE as a novel therapeutic target for potential treatment of pancreatic cancer.
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Affiliation(s)
- Junchen Pan
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Rui Liu
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Wenhua Lu
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Hongyu Peng
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Jing Yang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Qianrui Zhang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Tiantian Yu
- Metabolic Innovation Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bitao Huo
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China; Metabolic Innovation Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaoying Wei
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Haixi Liang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Lin Zhou
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Yameng Sun
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Yumin Hu
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Shijun Wen
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Jie Fu
- Department of Cellular and Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul J Chiao
- Department of Cellular and Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xiaojun Xia
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China
| | - Jinyun Liu
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China; Hainan Academy of Biomedical Sciences, Hainan Medical University, Haiko, Hainan, China.
| | - Peng Huang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, China; Metabolic Innovation Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
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Ungvari Z, Fekete M, Varga P, Lehoczki A, Munkácsy G, Fekete JT, Bianchini G, Ocana A, Buda A, Ungvari A, Győrffy B. Association between red and processed meat consumption and colorectal cancer risk: a comprehensive meta-analysis of prospective studies. GeroScience 2025:10.1007/s11357-025-01646-1. [PMID: 40210826 DOI: 10.1007/s11357-025-01646-1] [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: 02/11/2025] [Accepted: 04/01/2025] [Indexed: 04/12/2025] Open
Abstract
Increasing evidence suggests that red and processed meat consumption may elevate the risk of colorectal cancer (CRC), yet the magnitude and consistency of this association remain debated. This meta-analysis aims to quantify the relationship between red and processed meat intake and the risk of CRC, colon cancer, and rectal cancer using the most comprehensive set of prospective studies to date. We conducted a comprehensive search in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases from 1990 to November 2024, to identify relevant prospective studies examining red, processed, and total meat consumption in relation to colorectal, colon, and rectal cancer risk. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted for each study and pooled using a random-effects model to account for variability among studies. Statistical evaluation was executed using the online platform MetaAnalysisOnline.com. A total of 60 prospective studies were included. Red meat consumption was associated with a significantly increased risk of colon cancer (HR = 1.22, 95% CI 1.15-1.30), colorectal cancer (HR = 1.15, 95% CI 1.10-1.21), and rectal cancer (HR = 1.22, 95% CI 1.07-1.39). Processed meat consumption showed similar associations with increased risk for colon cancer (HR = 1.13, 95% CI 1.07-1.20), colorectal cancer (HR = 1.21, 95% CI 1.14-1.28), and rectal cancer (HR = 1.17, 95% CI 1.05-1.30). Total meat consumption also correlated with an elevated risk of colon cancer (HR = 1.22, 95% CI 1.11-1.35), colorectal cancer (HR = 1.17, 95% CI 1.12-1.22), and rectal cancer (HR = 1.28, 95% CI 1.10-1.48). This meta-analysis provides robust evidence that high consumption of red and processed meats is significantly associated with an increased risk of colorectal, colon, and rectal cancers. These findings reinforce current dietary recommendations advocating for the limitation of red and processed meat intake as part of cancer prevention strategies.
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Affiliation(s)
- Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College, Health Sciences Division/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
| | - Mónika Fekete
- Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
- Jozsef Fodor Center for Prevention and Healthy Aging, Semmelweis University, Budapest, Hungary
| | - Péter Varga
- Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
- Jozsef Fodor Center for Prevention and Healthy Aging, Semmelweis University, Budapest, Hungary
- Doctoral College, Health Sciences Division, Budapest, Hungary
| | - Andrea Lehoczki
- Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
- Jozsef Fodor Center for Prevention and Healthy Aging, Semmelweis University, Budapest, Hungary
- Doctoral College, Health Sciences Division, Budapest, Hungary
| | - Gyöngyi Munkácsy
- Department of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H- 1117, Budapest, Hungary
| | - János Tibor Fekete
- Department of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H- 1117, Budapest, Hungary
| | - Giampaolo Bianchini
- Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Alberto Ocana
- Experimental Therapeutics in Cancer Unit, Instituto de Investigación Sanitaria San Carlos (IdISSC), and CIBERONC, Madrid, Spain
- INTHEOS-CEU-START Laboratory, Facultad de Medicina, Universidad CEU San Pablo, 28668 Boadilla del Monte, Madrid, Spain
| | - Annamaria Buda
- Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
- Jozsef Fodor Center for Prevention and Healthy Aging, Semmelweis University, Budapest, Hungary
- Doctoral College, Health Sciences Division, Budapest, Hungary
| | - Anna Ungvari
- Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
- Jozsef Fodor Center for Prevention and Healthy Aging, Semmelweis University, Budapest, Hungary.
| | - Balázs Győrffy
- Jozsef Fodor Center for Prevention and Healthy Aging, Semmelweis University, Budapest, Hungary
- Department of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H- 1117, Budapest, Hungary
- Department of Biophysics, Medical School, University of Pecs, H- 7624, Pecs, Hungary
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Mahjourian M, Anjom-Shoae J, Mohammadi MA, Feinle-Bisset C, Sadeghi O. Associations of dietary fat types (MUFA, PUFA, SFA) and sources (animal, plant) with colorectal cancer risk: A comprehensive systematic review and dose-response meta-analysis of prospective cohort studies. Cancer Epidemiol 2025; 95:102768. [PMID: 39951860 DOI: 10.1016/j.canep.2025.102768] [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] [Received: 10/08/2024] [Revised: 01/25/2025] [Accepted: 02/05/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND AND OBJECTIVES While dietary fat intake has long been implicated as a risk factor for colorectal cancer, evidence from prospective cohort studies remains inconsistent. Moreover, previous meta-analyses examining the link between dietary fat intake and risk of colorectal cancer have not explored the dose-response relationships. Therefore, the current systematic review and meta-analysis was conducted to assess the dose-response associations of intakes of specific types (MUFA, PUFA and SFA) and sources (animal, plant) of dietary fat with the risk of colorectal, colon or rectal cancer. METHODS A comprehensive literature search of relevant online databases was performed to detect eligible studies until May 2023, identifying 21 prospective cohort studies with a total sample size of 2311,737 participants. The follow-up periods ranged from 7 to 19.4 years, during which 21,125 cases of colorectal, colon or rectal cancer were recorded. RESULTS Comparing extreme intake levels of total fat revealed the summary relative risk (RR) of 1.05 (95 % CI: 0.96-1.15) for colorectal cancer, 0.99 (95 % CI: 0.87-1.11) for colon cancer, and 1.09 (0.95 % CI: 0.93-1.13) for rectal cancer, indicating no significant association. Neither animal nor plant fat intake was associated with the risk of cancers. While no significant findings were also observed for MUFA or PUFA, the highest versus lowest comparison showed that a high intake of SFA was associated with a reduced risk of both colorectal 0.91 (95 % CI: 0.85-0.99) and colon cancer 0.86 (95 % CI: 0.75-0.98). However, in the non-linear dose-response analysis, the inverse association was seen within a certain range (<40 g/day). CONCLUSIONS These findings suggest that dietary SFA intake, less than 40 g/day, may have a protective effect against colorectal cancer. Further studies are needed to confirm our findings.
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Affiliation(s)
| | - Javad Anjom-Shoae
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | | | - Christine Feinle-Bisset
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - Omid Sadeghi
- Nutrition and Food Security Research Centre and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran; Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Ren YM, Zhuang ZY, Xie YH, Yang PJ, Xia TX, Xie YL, Liu ZH, Kang ZR, Leng XX, Lu SY, Zhang L, Chen JX, Xu J, Zhao EH, Wang Z, Wang M, Cui Y, Tan J, Liu Q, Jiang WH, Xiong H, Hong J, Chen YX, Chen HY, Fang JY. BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism. Cell Host Microbe 2024; 32:1519-1535.e7. [PMID: 39106870 DOI: 10.1016/j.chom.2024.07.012] [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] [Received: 06/02/2023] [Revised: 01/21/2024] [Accepted: 07/11/2024] [Indexed: 08/09/2024]
Abstract
Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.
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Affiliation(s)
- Yi-Meng Ren
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Zi-Yan Zhuang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Yuan-Hong Xie
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Peng-Jie Yang
- Chinese Academy of Sciences Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
| | - Tian-Xue Xia
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Yi-Le Xie
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Zhu-Hui Liu
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Zi-Ran Kang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Xiao-Xu Leng
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Shi-Yuan Lu
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Lu Zhang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Jin-Xian Chen
- Division of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jia Xu
- Division of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - En-Hao Zhao
- Division of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Zheng Wang
- Division of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Ming Wang
- Division of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Yun Cui
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Juan Tan
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Qiang Liu
- Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Wei-Hong Jiang
- Chinese Academy of Sciences Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
| | - Hua Xiong
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Jie Hong
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
| | - Hao-Yan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai 200001, China.
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Pouzou JG, Zagmutt FJ. Guidelines to restrict consumption of red meat to under 350 g/wk based on colorectal cancer risk are not consistent with health evidence. Nutrition 2024; 122:112395. [PMID: 38492553 DOI: 10.1016/j.nut.2024.112395] [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] [Received: 12/01/2023] [Revised: 01/25/2024] [Accepted: 02/10/2024] [Indexed: 03/18/2024]
Abstract
BACKGROUND The Nordic Nutrition Recommendations of 2023 (NNR2023) incorporate sustainability, health, and nutrition in their food-based dietary guidelines (FBDGs). NNR2023 recommends a consumption of ≤350 g/wk of unprocessed red meat (RM) based on association with colorectal cancer (CRC). This recommendation is lower than other FBDGs such as the World Cancer Research Fund (WCRF) recommendation it is based on (350-500 g/wk). OBJECTIVE To evaluate the empirical evidence and models cited by the NNR2023 to support the RM guidance. METHODS We fitted least-assumption (LA) dose-response (DR) models to the studies included in two systematic reviews (SRs) selected by NNR2023 on the RM and CRC association. We compared them against six parametric models reported in the two SRs. We evaluated the statistical significance of modeled relative risks (RR) at different consumption levels. RESULTS Twenty-one studies (20,604,188 patient-years) were analyzed. We found no significant association (RR = 1.04, 0.99-1.09) between 350g/wk of RM and CRC using the LA models, in agreement with the least restrictive models reported by Lescinsky et al., 2022 (RR = 1.11[0.89-1.38]) and WCRF (RR= 1.01[0.96-1.07]). The association was significant at 350 g/wk only under restricting assumptions such as monotonicity RR=1.3[1.01-1.64], and linearity RR = 1.06 [1.00-1.12]. No significant empirical association is observed under 567 g/wk based on evidence used by NNR2023. CONCLUSIONS The sources cited by NNR2023 do not support a consumption restriction of ≤350 g/wk of RM due to CRC, and other studies omitted by NNR2023 do not support association between RM and CRC. We show that model assumptions rather than empirical evidence drive this recommendation. Model uncertainty should be explicitly incorporated in FBDGs.
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Pouzou JG, Zagmutt FJ. Observational Dose-Response Meta-Analysis Methods May Bias Risk Estimates at Low Consumption Levels: The Case of Meat and Colorectal Cancer. Adv Nutr 2024; 15:100214. [PMID: 38521239 PMCID: PMC11061242 DOI: 10.1016/j.advnut.2024.100214] [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] [Received: 10/10/2023] [Revised: 03/07/2024] [Accepted: 03/11/2024] [Indexed: 03/25/2024] Open
Abstract
Observational studies of foods and health are susceptible to bias, particularly from confounding between diet and other lifestyle factors. Common methods for deriving dose-response meta-analysis (DRMA) may contribute to biased or overly certain risk estimates. We used DRMA models to evaluate the empirical evidence for colorectal cancer (CRC) association with unprocessed red meat (RM) and processed meats (PM), and the consistency of this association for low and high consumers under different modeling assumptions. Using the Global Burden of Disease project's systematic reviews as a start, we compiled a data set of studies of PM with 29 cohorts contributing 23,522,676 person-years and of 23 cohorts for RM totaling 17,259,839 person-years. We fitted DRMA models to lower consumers only [consumption < United States median of PM (21 g/d) or RM (56 g/d)] and compared them with DRMA models using all consumers. To investigate impacts of model selection, we compared classical DRMA models against an empirical model for both lower consumers only and for all consumers. Finally, we assessed if the type of reference consumer (nonconsumer or mixed consumer/nonconsumer) influenced a meta-analysis of the lowest consumption arm. We found no significant association with consumption of 50 g/d RM using an empirical fit with lower consumption (relative risk [RR] 0.93 (0.8-1.02) or all consumption levels (1.04 (0.99-1.10)), while classical models showed RRs as high as 1.09 (1.00-1.18) at 50g/day. PM consumption of 20 g/d was not associated with CRC (1.01 (0.87-1.18)) when using lower consumer data, regardless of model choice. Using all consumption data resulted in association with CRC at 20g/day of PM for the empirical models (1.07 (1.02-1.12)) and with as little as 1g/day for classical models. The empirical DRMA showed nonlinear, nonmonotonic relationships for PM and RM. Nonconsumer reference groups did not affect RM (P = 0.056) or PM (P = 0.937) association with CRC in lowest consumption arms. In conclusion, classical DRMA model assumptions and inclusion of higher consumption levels influence the association between CRC and low RM and PM consumption. Furthermore, a no-risk limit of 0 g/d consumption of RM and PM is inconsistent with the evidence.
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Affiliation(s)
- Jane G Pouzou
- EpiX Analytics, LLC. Fort Collins, CO, United States
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Erazo-Oliveras A, Muñoz-Vega M, Salinas ML, Wang X, Chapkin RS. Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk. FEBS J 2024; 291:1299-1352. [PMID: 36282100 PMCID: PMC10126207 DOI: 10.1111/febs.16665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 09/09/2022] [Accepted: 10/24/2022] [Indexed: 11/07/2022]
Abstract
Cellular membranes serve as an epicentre combining extracellular and cytosolic components with membranous effectors, which together support numerous fundamental cellular signalling pathways that mediate biological responses. To execute their functions, membrane proteins, lipids and carbohydrates arrange, in a highly coordinated manner, into well-defined assemblies displaying diverse biological and biophysical characteristics that modulate several signalling events. The loss of membrane homeostasis can trigger oncogenic signalling. More recently, it has been documented that select membrane active dietaries (MADs) can reshape biological membranes and subsequently decrease cancer risk. In this review, we emphasize the significance of membrane domain structure, organization and their signalling functionalities as well as how loss of membrane homeostasis can steer aberrant signalling. Moreover, we describe in detail the complexities associated with the examination of these membrane domains and their association with cancer. Finally, we summarize the current literature on MADs and their effects on cellular membranes, including various mechanisms of dietary chemoprevention/interception and the functional links between nutritional bioactives, membrane homeostasis and cancer biology.
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Affiliation(s)
- Alfredo Erazo-Oliveras
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Mónica Muñoz-Vega
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Michael L. Salinas
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Xiaoli Wang
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
| | - Robert S. Chapkin
- Program in Integrative Nutrition and Complex Diseases; Texas A&M University; College Station, Texas, 77843; USA
- Department of Nutrition; Texas A&M University; College Station, Texas, 77843; USA
- Center for Environmental Health Research; Texas A&M University; College Station, Texas, 77843; USA
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8
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Jiang W, Jin WL, Xu AM. Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities. Int J Biol Sci 2024; 20:2044-2071. [PMID: 38617549 PMCID: PMC11008265 DOI: 10.7150/ijbs.92274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 02/27/2024] [Indexed: 04/16/2024] Open
Abstract
Cholesterol is crucial for cell survival and growth, and dysregulation of cholesterol homeostasis has been linked to the development of cancer. The tumor microenvironment (TME) facilitates tumor cell survival and growth, and crosstalk between cholesterol metabolism and the TME contributes to tumorigenesis and tumor progression. Targeting cholesterol metabolism has demonstrated significant antitumor effects in preclinical and clinical studies. In this review, we discuss the regulatory mechanisms of cholesterol homeostasis and the impact of its dysregulation on the hallmarks of cancer. We also describe how cholesterol metabolism reprograms the TME across seven specialized microenvironments. Furthermore, we discuss the potential of targeting cholesterol metabolism as a therapeutic strategy for tumors. This approach not only exerts antitumor effects in monotherapy and combination therapy but also mitigates the adverse effects associated with conventional tumor therapy. Finally, we outline the unresolved questions and suggest potential avenues for future investigations on cholesterol metabolism in relation to cancer.
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Affiliation(s)
- Wen Jiang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, P. R. China
| | - Wei-Lin Jin
- Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
| | - A-Man Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, P. R. China
- Anhui Public Health Clinical Center, Hefei 230022, P. R. China
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9
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Linz MO, Lorincz-Comi N, Kuwatch AA, Cooper GS. Patient Decisions Regarding Rescheduling Colonoscopies Postponed Due to the COVID-19 Pandemic. Dig Dis Sci 2023; 68:4339-4349. [PMID: 37794293 DOI: 10.1007/s10620-023-08119-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 09/19/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND Due to the COVID-19 pandemic, elective colonoscopies were postponed in Ohio from 3/17/2020 to 5/1/2020. When the ban was lifted, canceled patients determined whether to reschedule their colonoscopy in the midst of the ongoing pandemic. AIMS We aim to determine whether demographic, colorectal cancer (CRC) risk, and COVID-19 morbidity and mortality risk factors are associated with rescheduling of colonoscopies canceled by the COVID-19 pandemic. METHODS A medical record review of 420 participants ages 40-74 at a midwestern academic health system with elective colonoscopies canceled from 3/17/2020 to 5/1/2020 due to the COVID-19 pandemic was performed. RESULTS More than half of participants (71.0%) rescheduled their colonoscopy within the next 8 months. Indication for colonoscopy being 'surveillance following adenoma', colonoscopy ordered by primary care provider rather than gastroenterologist, and dyslipidemia were independently associated with rescheduling colonoscopy. Higher body mass index, indication for colonoscopy being simply 'screening for CRC,' and stool testing were associated with not rescheduling. Diagnoses associated with colorectal cancer risk such as adenomas, personal or family history of colorectal cancer, and inflammatory bowel disease were not associated with rescheduling, nor were other comorbidities associated with increased COVID-19 severity. 4.5% (19/420) opted for stool fecal immunochemical test or Cologuard testing. CONCLUSIONS Most patients rescheduled their colonoscopy despite the risk of virus exposure, suggesting that concern of missed colorectal cancer diagnosis outweighed coronavirus concerns. Patient trust in referring providers may be important for rescheduling, and colonoscopy indications were independently associated with rescheduling status.
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Affiliation(s)
- Marguerite O Linz
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106-5066, USA
- Comprehensive Cancer Center (GSC), Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH, 44106-5066, USA
| | - Noah Lorincz-Comi
- Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106-5066, USA
| | - Abigail A Kuwatch
- University Hospitals Quality Care Network, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106-5066, USA
| | - Gregory S Cooper
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106-5066, USA.
- Comprehensive Cancer Center (GSC), Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH, 44106-5066, USA.
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10
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Di Y, Ding L, Gao L, Huang H. Association of meat consumption with the risk of gastrointestinal cancers: a systematic review and meta-analysis. BMC Cancer 2023; 23:782. [PMID: 37612616 PMCID: PMC10463360 DOI: 10.1186/s12885-023-11218-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 07/24/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable. Therefore, we performed a systematic review and meta-analysis of prospective cohort studies to estimate the association between meat consumption and gastrointestinal cancer risk. METHODS PubMed, EmBase, and the Cochrane library databases were searched systematically for eligible studies that investigated the relation between meat consumption and the risk of developing gastrointestinal cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), pancreatic cancer (PC), and hepatocellular carcinoma (HCC) throughout February, 2023. The pooled relative risk (RR) with 95% confidence interval (CI) was assigned as an effect estimate and calculated using a random-effects model with inverse variance weighting. RESULTS Forty cohorts comprising 3,780,590 individuals were selected for the final quantitative analysis. The summary results indicated that a higher red meat consumption was associated with an increased risk of CRC (RR: 1.09; 95% CI: 1.02-1.16; P = 0.007) and CC (RR: 1.13; 95% CI: 1.03-1.25; P = 0.011). Moreover, a higher processed meat consumption was associated with an increased risk of CRC (RR: 1.19; 95% CI: 1.13-1.26; P < 0.001), CC (RR: 1.24; 95% CI: 1.13-1.26; P < 0.001), and RC (RR: 1.24; 95% CI: 1.08-1.42; P = 0.002). Furthermore, a higher total consumption of red and processed meat was associated with an increased risk of CRC (RR: 1.13; 95% CI: 1.06-1.20; P < 0.001), CC (RR: 1.17; 95% CI: 1.04-1.33; P = 0.012), and RC (RR: 1.20; 95% CI: 1.04-1.39; P = 0.016). Finally, the strength of higher consumption of total red and processed meat with the risk of GC, and higher consumption of red meat with the risk of RC in subgroup of high adjusted level was lower than subgroup of moderate adjusted level, while the strength of higher consumption of processed meat with the risk of RC and HCC in subgroup of follow-up ≥ 10.0 years was higher than subgroup of follow-up < 10.0 years. CONCLUSIONS This study found that meat consumption was associated with an increased risk of CRC, CC, and RC, and dietary intervention could be considered an effective strategy in preventing CRC.
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Affiliation(s)
- Yan Di
- Department of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Lei Ding
- Department of Oncology Surgery/ Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
| | - Luying Gao
- Department of Ultrasond/Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongyan Huang
- Department of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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11
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Lescinsky H, Afshin A, Ashbaugh C, Bisignano C, Brauer M, Ferrara G, Hay SI, He J, Iannucci V, Marczak LB, McLaughlin SA, Mullany EC, Parent MC, Serfes AL, Sorensen RJD, Aravkin AY, Zheng P, Murray CJL. Health effects associated with consumption of unprocessed red meat: a Burden of Proof study. Nat Med 2022; 28:2075-2082. [PMID: 36216940 PMCID: PMC9556326 DOI: 10.1038/s41591-022-01968-z] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 07/26/2022] [Indexed: 12/19/2022]
Abstract
Characterizing the potential health effects of exposure to risk factors such as red meat consumption is essential to inform health policy and practice. Previous meta-analyses evaluating the effects of red meat intake have generated mixed findings and do not formally assess evidence strength. Here, we conducted a systematic review and implemented a meta-regression-relaxing conventional log-linearity assumptions and incorporating between-study heterogeneity-to evaluate the relationships between unprocessed red meat consumption and six potential health outcomes. We found weak evidence of association between unprocessed red meat consumption and colorectal cancer, breast cancer, type 2 diabetes and ischemic heart disease. Moreover, we found no evidence of an association between unprocessed red meat and ischemic stroke or hemorrhagic stroke. We also found that while risk for the six outcomes in our analysis combined was minimized at 0 g unprocessed red meat intake per day, the 95% uncertainty interval that incorporated between-study heterogeneity was very wide: from 0-200 g d-1. While there is some evidence that eating unprocessed red meat is associated with increased risk of disease incidence and mortality, it is weak and insufficient to make stronger or more conclusive recommendations. More rigorous, well-powered research is needed to better understand and quantify the relationship between consumption of unprocessed red meat and chronic disease.
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Affiliation(s)
- Haley Lescinsky
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Ashkan Afshin
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA
| | - Charlie Ashbaugh
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Catherine Bisignano
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Michael Brauer
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA
- School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Giannina Ferrara
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Simon I Hay
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA
| | - Jiawei He
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA
| | - Vincent Iannucci
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Laurie B Marczak
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Susan A McLaughlin
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Erin C Mullany
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Marie C Parent
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Audrey L Serfes
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Reed J D Sorensen
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Aleksandr Y Aravkin
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA
- Department of Applied Mathematics, University of Washington, Seattle, WA, USA
| | - Peng Zheng
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA
| | - Christopher J L Murray
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USA.
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12
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Zhang R, Zeng J, Liu W, Meng J, Wang C, Shi L, Yang S, Chang J, Xing D. The role of NPC1L1 in cancer. Front Pharmacol 2022; 13:956619. [PMID: 36034854 PMCID: PMC9399402 DOI: 10.3389/fphar.2022.956619] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Lipid metabolism appears to play significant roles in the development of cancer. Numerous studies have shown that the evolution of malignancies, including breast, prostate, and colorectal cancers, involves cholesterol in a profound manner. A crucial part in the intestinal absorption of cholesterol is played by Niemann–Pick C1-like 1 (NPC1L1), a cholesterol transporter protein that is widely expressed in the small intestine and liver. The importance of NPC1L1 in tumor prognosis has been demonstrated in investigations in the interim. NPC1L1 also has the potential to develop into a new therapeutic target and a cancer marker. There is, however, no comprehensive review that summarizes NPC1L1’s function in cancer. To this end, we outlined NPC1L1’s functions in carcinogenesis and treatment, along with resources that can be used to further comprehend the connection between NPC1L1 and tumors.
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Affiliation(s)
- Renshuai Zhang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Jun Zeng
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Wenjing Liu
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Jingsen Meng
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Chao Wang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Lingyu Shi
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Shanbo Yang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Jing Chang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Dongming Xing
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Life Sciences, Tsinghua University, Beijing, China
- *Correspondence: Dongming Xing,
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13
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Wan Y, Wu K, Wang L, Yin K, Song M, Giovannucci EL, Willett WC. Dietary fat and fatty acids in relation to risk of colorectal cancer. Eur J Nutr 2022; 61:1863-1873. [DOI: 10.1007/s00394-021-02777-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 12/06/2021] [Indexed: 12/31/2022]
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El Asri A, Ouldim K, Bouguenouch L, Sekal M, Moufid FZ, Kampman E, Huybrechts I, Gunter MJ, Abbaoui S, Znati K, Karkouri M, Kinany KE, Hatime Z, Deoula MMS, Chbani L, Zarrouq B, El Rhazi K. Dietary Fat Intake and KRAS Mutations in Colorectal Cancer in a Moroccan Population. Nutrients 2022; 14:318. [PMID: 35057499 PMCID: PMC8779768 DOI: 10.3390/nu14020318] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/05/2022] [Accepted: 01/09/2022] [Indexed: 01/27/2023] Open
Abstract
Epidemiologic data support an association between diet and mutations in the Kirsten-ras (KRAS) gene involved in colorectal cancer (CRC) development. This study aimed to explore the associations between fat intake and KRAS mutations in codons 12 and 13 in cases of CRC in the Moroccan population. A multicenter case-series study nested in a large-scale Moroccan CRC case-control study was conducted. Among all CRC cases recruited, 151 specimens were available for the DNA mutation analysis. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cis) for KRAS mutation status according to the fat intake variables. A KRAS mutation was detected in the CRC tumor of 34.4% of the patients among whom 65.4% had a single mutation at codon 12 and 34.6% had a single mutation at codon 13. Compared to low levels of consumption, a positive association was observed between high polyunsaturated fatty acids (PUFA) consumption (>16.9 g/day) and prevalence of KRAS mutations (OR = 2.15, 95% CI = 1.01-4.59). No statistically significant associations were observed for total fat, monounsaturated fatty acids, saturated fatty acids and KRAS mutations. The results of this study suggest that PUFA may be relevant in the etiology of CRC, possibly through the generation of G > A transitions at the KRAS oncogene. Further studies are needed to verify and explain this finding.
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Affiliation(s)
- Achraf El Asri
- Laboratory of Epidemiology and Research in Health Sciences, Department of Epidemiology and Public Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.E.K.); (Z.H.); (M.M.S.D.); (B.Z.); (K.E.R.)
| | - Karim Ouldim
- Medical Genetics and Oncogenetics Unit, Hassan II University Hospital, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.O.); (L.B.); (F.Z.M.)
- Cancer Research Institute, Fez 20192, Morocco
| | - Laila Bouguenouch
- Medical Genetics and Oncogenetics Unit, Hassan II University Hospital, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.O.); (L.B.); (F.Z.M.)
| | - Mohammed Sekal
- Department of Anatomy and Cytopathology, Hassan II University Hospital, Sidi Mohammed Ben Abdallah University, Fez 30000, Morocco; (M.S.); (L.C.)
| | - Fatima Zahra Moufid
- Medical Genetics and Oncogenetics Unit, Hassan II University Hospital, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.O.); (L.B.); (F.Z.M.)
| | - Ellen Kampman
- Division of Human Nutrition and Health, Wageningen University and Research, 69000 Wageningen, The Netherlands;
| | - Inge Huybrechts
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France; (I.H.); (M.J.G.)
| | - Marc J. Gunter
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France; (I.H.); (M.J.G.)
| | - Sanae Abbaoui
- Faculty of Medicine and Pharmacy, Ibn Zohr University, Agadir 80035, Morocco;
| | - Kaoutar Znati
- Department of Pathology, Ibn Sina University Hospital, Mohammed V University, Rabat 10001, Morocco;
| | - Mehdi Karkouri
- Pathologic Anatomy and Cytology Laboratory, Ibn Rochd University Hospital, Casablanca 20360, Morocco;
| | - Khaoula El Kinany
- Laboratory of Epidemiology and Research in Health Sciences, Department of Epidemiology and Public Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.E.K.); (Z.H.); (M.M.S.D.); (B.Z.); (K.E.R.)
| | - Zineb Hatime
- Laboratory of Epidemiology and Research in Health Sciences, Department of Epidemiology and Public Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.E.K.); (Z.H.); (M.M.S.D.); (B.Z.); (K.E.R.)
| | - Meimouna Mint Sidi Deoula
- Laboratory of Epidemiology and Research in Health Sciences, Department of Epidemiology and Public Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.E.K.); (Z.H.); (M.M.S.D.); (B.Z.); (K.E.R.)
| | - Laila Chbani
- Department of Anatomy and Cytopathology, Hassan II University Hospital, Sidi Mohammed Ben Abdallah University, Fez 30000, Morocco; (M.S.); (L.C.)
| | - Btissame Zarrouq
- Laboratory of Epidemiology and Research in Health Sciences, Department of Epidemiology and Public Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.E.K.); (Z.H.); (M.M.S.D.); (B.Z.); (K.E.R.)
- Department of Biology and Geology, Teachers Training College (Ecole Normale Superieure), Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco
| | - Karima El Rhazi
- Laboratory of Epidemiology and Research in Health Sciences, Department of Epidemiology and Public Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco; (K.E.K.); (Z.H.); (M.M.S.D.); (B.Z.); (K.E.R.)
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15
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Li Y, Sun M. Is dietary cholesterol intake associated with risk of colorectal cancer? An updated systematic review and meta-analysis of observational studies. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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16
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Kwon RJ, Park EJ, Lee SY, Lee Y, Hwang C, Kim C, Cho YH. Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study. Lipids Health Dis 2021; 20:104. [PMID: 34511128 PMCID: PMC8436523 DOI: 10.1186/s12944-021-01539-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/31/2021] [Indexed: 11/10/2022] Open
Abstract
Background Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown. Methods Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann–Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC. Results The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan–Meier and multivariate regression analyses. Conclusions As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.
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Affiliation(s)
- Ryuk Jun Kwon
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Eun-Ju Park
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Sang Yeoup Lee
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Youngin Lee
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Chungsu Hwang
- Department of Pathology, Pusan National University School of Medicine, 626-780, Yangsan, South Korea
| | - Choongrak Kim
- Department of Statistics, Pusan National University, 609-735, Busan, South Korea
| | - Young Hye Cho
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea.
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17
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Qu R, Ma Y, Tao L, Bao X, Zhou X, Wang B, Li F, Lu S, Tuo L, Zhan S, Zhang Z, Fu W. Features of colorectal cancer in China stratified by anatomic sites: A hospital-based study conducted in university-affiliated hospitals from 2014 to 2018. Chin J Cancer Res 2021; 33:500-511. [PMID: 34584375 PMCID: PMC8435820 DOI: 10.21147/j.issn.1000-9604.2021.04.07] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 07/26/2021] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE The clinical and biological characteristics of colorectal cancer have been found to differ depending on the anatomic site of the cancer. However, for Chinese patients, there is limited information on the proportion of cases at each site and the related features. In this study, we explored the location, distribution and other features of colorectal cancers at each anatomic site in Chinese patients. METHODS We conducted a hospital-based study using hospitalization summary reports from 10 Peking University-affiliated hospitals from 2014 to 2018; the reports covered a total of 2,097,347 hospitalizations. Incident cases were chosen as the study population, and their epidemiological features were further analyzed. RESULTS A total of 20,739 colorectal cancer patients were identified. Rectum was the most common location (48.3%) of the cancer, whereas the proportions of patients with distal and proximal colon cancer were 24.5% and 18.6%, respectively. Patients with rectal cancer were predominantly male and were the youngest for all anatomical sites (each P<0.001). The highest proportion of emergency admissions, the longest hospital stays and the highest hospitalization costs were found in patients with proximal colon cancer (each P<0.001). The proximal colon cancer subgroup included the highest proportions of patients with medical histories of cholecystectomy, cholecystolithiasis and/or gallbladder polyps and appendectomy (P=0.009, P<0.001 and P<0.001, respectively). The distal colon cancer subgroup included the highest proportions of patients with medical histories of diabetes and hypertension (P<0.001, respectively). CONCLUSIONS The patterns of colorectal cancer observed in this study differ from those reported for Western patients and show a significantly higher proportion of patients with rectal cancer. Different epidemiological features were also found based on anatomic sites. Further studies based on tumor location should be conducted to facilitate more accurate screening and treatment.
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Affiliation(s)
- Ruize Qu
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Yanpeng Ma
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Liyuan Tao
- Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing 100191, China
| | - Xiaoyuan Bao
- Medical Information Center, Peking University Health Science Center, Beijing 100191, China
| | - Xin Zhou
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Bingyan Wang
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Fei Li
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Siyi Lu
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Lin Tuo
- Department of Hospital Management, Peking University Health Science Center, Beijing 100191, China
| | - Siyan Zhan
- Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing 100191, China
| | - Zhipeng Zhang
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Wei Fu
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
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18
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Farvid MS, Sidahmed E, Spence ND, Mante Angua K, Rosner BA, Barnett JB. Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies. Eur J Epidemiol 2021; 36:937-951. [PMID: 34455534 DOI: 10.1007/s10654-021-00741-9] [Citation(s) in RCA: 181] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 03/15/2021] [Indexed: 02/06/2023]
Abstract
Red meat and processed meat consumption has been hypothesized to increase risk of cancer, but the evidence is inconsistent. We performed a systematic review and meta-analysis of prospective studies to summarize the evidence of associations between consumption of red meat (unprocessed), processed meat, and total red and processed meat with the incidence of various cancer types. We searched in MEDLINE and EMBASE databases through December 2020. Using a random-effect meta-analysis, we calculated the pooled relative risk (RR) and 95% confidence intervals (CI) of the highest versus the lowest category of red meat, processed meat, and total red and processed meat consumption in relation to incidence of various cancers. We identified 148 published articles. Red meat consumption was significantly associated with greater risk of breast cancer (RR = 1.09; 95% CI = 1.03-1.15), endometrial cancer (RR = 1.25; 95% CI = 1.01-1.56), colorectal cancer (RR = 1.10; 95% CI = 1.03-1.17), colon cancer (RR = 1.17; 95% CI = 1.09-1.25), rectal cancer (RR = 1.22; 95% CI = 1.01-1.46), lung cancer (RR = 1.26; 95% CI = 1.09-1.44), and hepatocellular carcinoma (RR = 1.22; 95% CI = 1.01-1.46). Processed meat consumption was significantly associated with a 6% greater breast cancer risk, an 18% greater colorectal cancer risk, a 21% greater colon cancer risk, a 22% greater rectal cancer risk, and a 12% greater lung cancer risk. Total red and processed meat consumption was significantly associated with greater risk of colorectal cancer (RR = 1.17; 95% CI = 1.08-1.26), colon cancer (RR = 1.21; 95% CI = 1.09-1.34), rectal cancer (RR = 1.26; 95% CI = 1.09-1.45), lung cancer (RR = 1.20; 95% CI = 1.09-1.33), and renal cell cancer (RR = 1.19; 95% CI = 1.04-1.37). This comprehensive systematic review and meta-analysis study showed that high red meat intake was positively associated with risk of breast cancer, endometrial cancer, colorectal cancer, colon cancer, rectal cancer, lung cancer, and hepatocellular carcinoma, and high processed meat intake was positively associated with risk of breast, colorectal, colon, rectal, and lung cancers. Higher risk of colorectal, colon, rectal, lung, and renal cell cancers were also observed with high total red and processed meat consumption.
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Affiliation(s)
- Maryam S Farvid
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Elkhansa Sidahmed
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Nicholas D Spence
- Department of Sociology and Department of Health and Society, University of Toronto, Toronto, ON, Canada
| | | | - Bernard A Rosner
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Junaidah B Barnett
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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19
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Abstract
The incidence and mortality associated with colorectal cancer (CRC) diagnosed in patients under the age of 50 have been steadily increasing. The exact etiology of these epidemiologic trends is unclear. This chapter will provide a comprehensive review on the topic of early age onset colorectal cancer (EAO-CRC), defined as colorectal cancer (CRC) diagnosed in patients under the age of 50. Topics reviewed will include the epidemiology of EAO-CRC around the world, clinical and pathological features of EAO-CRC in contrast to later age onset CRC (CRC diagnosed on those over the age of 50) and the observed molecular and somatic characteristics. This chapter will review the etiologies to EAO-CRC and the established, as well as proposed risk factors for disease. Evidence-based approaches to prevention, early detection, treatment and survivorship will be presented.
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Affiliation(s)
- Swati G Patel
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, United States.
| | - Caitlin C Murphy
- Division of Epidemiology, Department of Population & Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Christopher H Lieu
- Division of Medical Oncology, Gastrointestinal Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Heather Hampel
- Division of Human Genetics, Biospecimen Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States
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20
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Nguyen S, Li H, Yu D, Cai H, Gao J, Gao Y, Luu H, Tran H, Xiang YB, Zheng W, Shu XO. Dietary fatty acids and colorectal cancer risk in men: A report from the Shanghai Men's Health Study and a meta-analysis. Int J Cancer 2021; 148:77-89. [PMID: 32638381 PMCID: PMC11067784 DOI: 10.1002/ijc.33196] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 06/26/2020] [Accepted: 06/29/2020] [Indexed: 12/21/2022]
Abstract
Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59 986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) was not significantly associated with CRC risk. Multivariate hazard ratios (HRs) and respective 95% confidence intervals (CIs) for Quartile 4 vs Quartile 1 were 0.92 (0.74-1.14; Ptrend = 0.47) for SFA, 0.95 (0.79-1.16; Ptrend = 0.74) for MUFA and 1.18 (0.95-1.46; Ptrend = 0.21) for PUFA. No significant associations were found for total n-6 PUFA or total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid and eicosapentaenoic acid were associated with 11% to 12% reduced risk, and linoleic acid a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men.
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Affiliation(s)
- Sang Nguyen
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Honglan Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
| | - Danxia Yu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Hui Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Jing Gao
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, No.227 South Chongqing Road, Shanghai 200025, PR China
| | - Yutang Gao
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
| | - Hung Luu
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Huong Tran
- Hanoi Medical University, Vietnam National Cancer Institute, Hanoi, Vietnam
| | - Yong-Bing Xiang
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
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21
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Loke YL, Chew MT, Ngeow YF, Lim WWD, Peh SC. Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota. Front Cell Infect Microbiol 2020; 10:603086. [PMID: 33364203 PMCID: PMC7753026 DOI: 10.3389/fcimb.2020.603086] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 10/28/2020] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk.
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Affiliation(s)
- Yean Leng Loke
- Centre for Biomedical Physics, School of Healthcare and Medical Sciences, Sunway University, Petaling Jaya, Malaysia
| | - Ming Tsuey Chew
- Centre for Biomedical Physics, School of Healthcare and Medical Sciences, Sunway University, Petaling Jaya, Malaysia
| | - Yun Fong Ngeow
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Malaysia.,Centre for Research on Communicable Diseases, Universiti Tunku Abdul Rahman, Kajang, Malaysia
| | - Wendy Wan Dee Lim
- Department of Gastroenterology, Sunway Medical Centre, Petaling Jaya, Malaysia
| | - Suat Cheng Peh
- Ageing Health and Well-Being Research Centre, Sunway University, Petaling Jaya, Malaysia.,Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, Petaling Jaya, Malaysia
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22
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Yang Z, Wei X, Pan Y, Min Z, Xu J, Yu B. Colon cancer combined with obesity indicates improved survival- research on relevant mechanism. Aging (Albany NY) 2020; 12:23778-23794. [PMID: 33197880 PMCID: PMC7762486 DOI: 10.18632/aging.103972] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 07/30/2020] [Indexed: 12/11/2022]
Abstract
Obesity contributes to the incidence of various tumors, including colon cancer. However, the impact of obesity on patients’ survival and related mechanisms remains unclear. Multi-omics data of 227 cases of colon cancer patients combined with clinical characteristics data were acquired from The Cancer Genome Atlas (TCGA) database. We confirmed obesity as an independent prognostic factor for improved overall survival of colon cancer patients. We demonstrated that hypoxia pathways were repressed in obese patients by regulating miR-210. Immune checkpoints PD-1 and LAG3 were also downregulated in obese patients, which indicated enhanced immune surveillance. The frequency of PIK3CA and KRAS mutations was decreased in obese patients. The sites and types of TP53 mutation were alternated in obesity patients. In conclusion, our research demonstrated the potential mechanisms of prolonged survival in colon cancer patients combined with obesity, which may provide potential value for improving the prognosis of colon cancer.
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Affiliation(s)
- Zhou Yang
- Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
| | - Xiyi Wei
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu, China
| | - Yitong Pan
- Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211116, China
| | - Zhijun Min
- Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
| | - Jingyuan Xu
- Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.,Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Bo Yu
- Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.,Department of General Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai 201399, China
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23
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Ha NT, Lee CH. Roles of Farnesyl-Diphosphate Farnesyltransferase 1 in Tumour and Tumour Microenvironments. Cells 2020; 9:cells9112352. [PMID: 33113804 PMCID: PMC7693003 DOI: 10.3390/cells9112352] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 10/23/2020] [Accepted: 10/24/2020] [Indexed: 12/14/2022] Open
Abstract
Farnesyl-diphosphate farnesyltransferase 1 (FDFT1, squalene synthase), a membrane-associated enzyme, synthesizes squalene via condensation of two molecules of farnesyl pyrophosphate. Accumulating evidence has noted that FDFT1 plays a critical role in cancer, particularly in metabolic reprogramming, cell proliferation, and invasion. Based on these advances in our knowledge, FDFT1 could be a potential target for cancer treatment. This review focuses on the contribution of FDFT1 to the hallmarks of cancer, and further, we discuss the applicability of FDFT1 as a cancer prognostic marker and target for anticancer therapy.
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24
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Jiang T, Zhang G, Lou Z. Role of the Sterol Regulatory Element Binding Protein Pathway in Tumorigenesis. Front Oncol 2020; 10:1788. [PMID: 33014877 PMCID: PMC7506081 DOI: 10.3389/fonc.2020.01788] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Accepted: 08/11/2020] [Indexed: 12/15/2022] Open
Abstract
Metabolic changes are a major feature of tumors, including various metabolic forms, such as energy, lipid, and amino acid metabolism. Sterol regulatory element binding proteins (SREBPs) are important modules in regulating lipid metabolism and play an essential role in metabolic diseases. In the previous decades, the regulatory range of SREBPs has been markedly expanded. It was found that SREBPs also played a critical role in tumor development. SREBPs are involved in energy supply, lipid supply, immune environment and inflammatory environment shaping in tumor cells, and as a protective umbrella to support the malignant proliferation of tumor cells. Natural medicine and traditional Chinese medicine, as an important part of drug therapy, demonstrates the multifaceted effects of SREBPs regulation. This review summarizes the core processes in the involvement of SREBPs in tumors and provides a comprehensive understanding of the pathways through which natural drugs target the SREBP pathway and regulate tumor progression.
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Affiliation(s)
- Tao Jiang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Guangji Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhaohuan Lou
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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25
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Warsinggih, Irawan B, Labeda I, Lusikooy RE, Sampetoding S, Kusuma MI, Uwuratuw JA, Syarifuddin E, Prihantono, Faruk M. Association of superoxide dismutase enzyme with staging and grade of differentiation colorectal cancer: A cross-sectional study. Ann Med Surg (Lond) 2020; 58:194-199. [PMID: 32994983 PMCID: PMC7505864 DOI: 10.1016/j.amsu.2020.08.032] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 08/17/2020] [Indexed: 02/09/2023] Open
Abstract
Introduction The increase of superoxide dismutase (SOD) level in colorectal cancer (CRC) patients based on the examination of staging and grade of differentiation still evidently represents a clinical problem. SOD level raises at a certain staging and reduce at a certain grade of differentiation. For that reason, this study aimed to assess the association between SOD and the variables analyzed in this study. Materials and methods This study was observational study using a cross-sectional research design aimed to measure the association between SOD and staging as well as grade of differentiation in CRC incidence. The study was conducted in our institution from January until March 2018. Results Statistical analyses of the data derived from the laboratory indicated that age and histopathological examination (TNM staging) had statistically significant correlation with SOD1 level. This significant correlation was proven from results of the statistical analyses of each variable at p = 0.039 (age) and p = 0.001 (TNM staging) respectively. Subsequent tests concerning the correlation between age and TNM staging on SOD1 level revealed that the study samples in the category of 30-49 age years old showed statistically significant correlation with SOD1 level with p = 0.009. Conclusion The increase of grade of differentiation was proportional to the increase of SOD1 level as antioxidant against cancer in CRC patients.
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Affiliation(s)
- Warsinggih
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Budi Irawan
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Ibrahim Labeda
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Ronald Erasio Lusikooy
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Samuel Sampetoding
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - M Ihwan Kusuma
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Julianus Aboyaman Uwuratuw
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Erwin Syarifuddin
- Division of Digestive, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Prihantono
- Division of Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Muhammad Faruk
- Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
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26
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Gachpazan M, Kashani H, Khazaei M, Hassanian SM, Rezayi M, Asgharzadeh F, Ghayour-Mobarhan M, Ferns GA, Avan A. The Impact of Statin Therapy on the Survival of Patients with Gastrointestinal Cancer. Curr Drug Targets 2020; 20:738-747. [PMID: 30539694 DOI: 10.2174/1389450120666181211165449] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 10/25/2018] [Accepted: 12/05/2018] [Indexed: 12/13/2022]
Abstract
Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins affect several potential pathways, including cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website clinicaltrials.gov. Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting. However, randomized controlled trials on specific cancer types in relation to statin use, as well as studies on populations without a clinical indication for using statins, have elucidated some potential underlying biological mechanisms, and the investigation of different statins is probably warranted. It would be useful for these trials to incorporate the assessment of tumour biomarkers predictive of statin response in their design. This review summarizes the recent preclinical and clinical studies that assess the application of statins in the treatment of gastrointestinal cancers with particular emphasize on their association with cancer risk.
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Affiliation(s)
- Meysam Gachpazan
- Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Modern Sciences and Technologies; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hoda Kashani
- Department of Modern Sciences and Technologies; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biochemistry; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Rezayi
- Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Modern Sciences and Technologies; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fereshteh Asgharzadeh
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, United Kingdom
| | - Amir Avan
- Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Modern Sciences and Technologies; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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27
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The Pivotal Role of the Dysregulation of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets. Cancers (Basel) 2020; 12:cancers12061410. [PMID: 32486083 DOI: 10.3390/cancers12061410] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/23/2020] [Accepted: 05/28/2020] [Indexed: 12/12/2022] Open
Abstract
Cholesterol plays an important role in cellular homeostasis by maintaining the rigidity of cell membranes, providing a medium for signaling transduction, and being converted into other vital macromolecules, such as sterol hormones and bile acids. Epidemiological studies have shown the correlation between cholesterol content and cancer incidence worldwide. Accumulating evidence has shown the emerging roles of the dysregulation of cholesterol metabolism in cancer development. More specifically, recent reports have shown the distinct role of cholesterol in the suppression of immune cells, regulation of cell survival, and modulation of cancer stem cells in cancer. Here, we provide a comprehensive review of the epidemiological analysis, functional roles, and mechanistic action of cholesterol homeostasis in regard to its contribution to cancer development. Based on the existing data, cholesterol homeostasis is identified to be a new key player in cancer pathogenesis. Lastly, we also discuss the therapeutic implications of natural compounds and cholesterol-lowering drugs in cancer prevention and treatment. In conclusion, intervention in cholesterol metabolism may offer a new therapeutic avenue for cancer treatment.
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28
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Chiodi I, Mondello C. Life style factors, tumor cell plasticity and cancer stem cells. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2020; 784:108308. [PMID: 32430096 DOI: 10.1016/j.mrrev.2020.108308] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 12/15/2022]
Abstract
Cancers are heterogeneous tissues and a layer of heterogeneity is determined by the presence of cells showing stemness traits, known as cancer stem cells (CSCs). Evidence indicates that CSCs are important players in tumor development, progression and relapse. Oncogenic transformation of normal stem cells can give rise to CSCs, but CSCs can also originate from de-differentiation of bulk tumor cells. Thus, factors promoting the increase of normal stem cell pools or stimulating the acquisition of stemness features by tumor cells can have serious consequences on cancer origin and progression. In this review, we will first give an overview of the CSC model of cancer development and we will then discuss the role of life style factors, such as high caloric diet, alcohol drinking and smoking, on the widening of stem cell pools and the induction of CSC features in tumors. Finally, we will discuss some healthy life style factors that can help to prevent cancer.
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Affiliation(s)
- Ilaria Chiodi
- Istituto di Genetica Molecolare L. L. Cavalli-Sforza, CNR, via Abbiategrasso 207, 27100, Pavia, Italy
| | - Chiara Mondello
- Istituto di Genetica Molecolare L. L. Cavalli-Sforza, CNR, via Abbiategrasso 207, 27100, Pavia, Italy.
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29
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Cholesterol and beyond - The role of the mevalonate pathway in cancer biology. Biochim Biophys Acta Rev Cancer 2020; 1873:188351. [PMID: 32007596 DOI: 10.1016/j.bbcan.2020.188351] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/14/2020] [Accepted: 01/30/2020] [Indexed: 02/07/2023]
Abstract
Cancer is a multifaceted global disease. Transformation of a normal to a malignant cell takes several steps, including somatic mutations, epigenetic alterations, metabolic reprogramming and loss of cell growth control. Recently, the mevalonate pathway has emerged as a crucial regulator of tumor biology and a potential therapeutic target. This pathway controls cholesterol production and posttranslational modifications of Rho-GTPases, both of which are linked to several key steps of tumor progression. Inhibitors of the mevalonate pathway induce pleiotropic antitumor-effects in several human malignancies, identifying the pathway as an attractive candidate for novel therapies. In this review, we will provide an overview about the role and regulation of the mevalonate pathway in certain aspects of cancer initiation and progression and its potential for therapeutic intervention in oncology.
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30
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Visweswaran M, Arfuso F, Warrier S, Dharmarajan A. Aberrant lipid metabolism as an emerging therapeutic strategy to target cancer stem cells. Stem Cells 2019; 38:6-14. [PMID: 31648395 DOI: 10.1002/stem.3101] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 08/25/2019] [Accepted: 09/10/2019] [Indexed: 12/12/2022]
Abstract
Emerging evidence in cancer metabolomics has identified reprogrammed metabolic pathways to be a major hallmark of cancer, among which deregulated lipid metabolism is a prominent field receiving increasing attention. Cancer stem cells (CSCs) comprise <0.1% of the tumor bulk and possess high self-renewal, tumor-initiating properties, and are responsible for therapeutic resistance, disease recurrence, and tumor metastasis. Hence, it is imperative to understand the metabolic rewiring occurring in CSCs, especially their lipid metabolism, on which there have been recent reports. CSCs rely highly upon lipid metabolism for maintaining their stemness properties and fulfilling their biomass and energy demands, ultimately leading to cancer growth and invasion. Hence, in this review we will shed light on the aberrant lipid metabolism that CSCs exploit to boost their survival, which comprises upregulation in de novo lipogenesis, lipid droplet synthesis, lipid desaturation, and β-oxidation. Furthermore, the metabolic regulators involved in the process, such as key lipogenic enzymes, are also highlighted. Finally, we also summarize the therapeutic strategies targeting the key regulators involved in CSCs' lipid metabolism, which thereby demonstrates the potential to develop powerful and novel therapeutics against the CSC lipid metabolome.
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Affiliation(s)
- Malini Visweswaran
- Stem Cell and Cancer Biology Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Western Australia, Australia
| | - Frank Arfuso
- Stem Cell and Cancer Biology Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Western Australia, Australia
| | - Sudha Warrier
- Division of Cancer Stem Cells and Cardiovascular Regeneration, School of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India
| | - Arun Dharmarajan
- Stem Cell and Cancer Biology Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Western Australia, Australia.,Department of Biomedical Sciences, Faculty of Biomedical Sciences, Technology and Research, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India
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Yang J, McDowell A, Kim EK, Seo H, Lee WH, Moon CM, Kym SM, Lee DH, Park YS, Jee YK, Kim YK. Development of a colorectal cancer diagnostic model and dietary risk assessment through gut microbiome analysis. Exp Mol Med 2019; 51:1-15. [PMID: 31582724 PMCID: PMC6802675 DOI: 10.1038/s12276-019-0313-4] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 06/09/2019] [Accepted: 06/25/2019] [Indexed: 12/15/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common form of cancer and poses a critical public health threat due to the global spread of westernized diets high in meat, cholesterol, and fat. Although the link between diet and colorectal cancer has been well established, the mediating role of the gut microbiota remains elusive. In this study, we sought to elucidate the connection between the gut microbiota, diet, and CRC through metagenomic analysis of bacteria isolated from the stool of CRC (n = 89) and healthy (n = 161) subjects. This analysis yielded a dozen genera that were significantly altered in CRC patients, including increased Bacteroides, Fusobacterium, Dorea, and Porphyromonas prevalence and diminished Pseudomonas, Prevotella, Acinetobacter, and Catenibacterium carriage. Based on these altered genera, we developed two novel CRC diagnostic models through stepwise selection and a simplified model using two increased and two decreased genera. As both models yielded strong AUC values above 0.8, the simplified model was applied to assess diet-based CRC risk in mice. Mice fed a westernized high-fat diet (HFD) showed greater CRC risk than mice fed a regular chow diet. Furthermore, we found that nonglutinous rice, glutinous rice, and sorghum consumption reduced CRC risk in HFD-fed mice. Collectively, these findings support the critical mediating role of the gut microbiota in diet-induced CRC risk as well as the potential of dietary grain intake to reduce microbiota-associated CRC risk. Further study is required to validate the diagnostic prediction models developed in this study as well as the preventive potential of grain consumption to reduce CRC risk.
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Affiliation(s)
- Jinho Yang
- MD Healthcare Inc., Seoul, Republic of Korea
- Department of Health and Safety Convergence Science, Korea University, Seoul, Republic of Korea
| | | | | | - Hochan Seo
- MD Healthcare Inc., Seoul, Republic of Korea
| | - Won Hee Lee
- MD Healthcare Inc., Seoul, Republic of Korea
| | - Chang-Mo Moon
- Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Sung-Min Kym
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea
| | - Young-Koo Jee
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea.
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Yu B, Zhang M, Chen J, Wang L, Peng X, Zhang X, Wang H, Wang A, Zhao D, Pang D, OuYang H, Tang X. Abnormality of hepatic triglyceride metabolism in Apc Min/+ mice with colon cancer cachexia. Life Sci 2019; 227:201-211. [PMID: 31002917 DOI: 10.1016/j.lfs.2019.04.041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 04/10/2019] [Accepted: 04/16/2019] [Indexed: 01/01/2023]
Abstract
AIMS Colorectal cancer syndrome has been one of the greatest concerns in the world. Although several epidemiological studies have shown that hepatic low lipoprotein lipase (LPL) mRNA expression may be associated with dyslipidemia and tumor progression, it is still not known whether the liver plays an essential role in hyperlipidemia of ApcMin/+ mice. MAIN METHODS We measured the expression of metabolic enzymes that involved fatty acid uptake, de novo lipogenesis (DNL), β-oxidation and investigated hepatic triglyceride production in the liver of wild-type and ApcMin/+ mice. KEY FINDINGS We found that hepatic fatty acid uptake and DNL decreased, but there was no significant difference in fatty acid β-oxidation. Interestingly, the production of hepatic very low-density lipoprotein-triglyceride (VLDL-TG) decreased at 20 weeks of age, but marked steatosis was observed in the livers of the ApcMin/+ mouse. To further explore hypertriglyceridemia, we assessed the function of hepatic glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) for the first time. GPIHBP1 is governed by the transcription factor octamer-binding transcription factor-1 (Oct-1) which are involved in the nuclear factor-κB (NF-κB) signaling pathway in the liver of ApcMin/+ mice. Importantly, it was also confirmed that sn50 (100 μg/mL, an inhibitor of the NF-κB) reversed the tumor necrosis factor α (TNFα)-induced Oct-1 and GPIHBP1 reduction in HepG2 cells. SIGNIFICANCE Altogether, these findings highlighted a novel role of GPIHBP1 that might be responsible for hypertriglyceridemia in ApcMin/+ mice. Hypertriglyceridemia in these mice may be associated with their hepatic lipid metabolism development.
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Affiliation(s)
- Biao Yu
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Mingjun Zhang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Jiahuan Chen
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Lingyu Wang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Xiaohuan Peng
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Xinwei Zhang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - He Wang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Anbei Wang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Dazhong Zhao
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Daxin Pang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Hongsheng OuYang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China
| | - Xiaochun Tang
- Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, No.5333 Xi'an Road, Lvyuan District, Changchun 130062, Jilin Province, China.
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Goncalves MD, Hopkins BD, Cantley LC. Dietary Fat and Sugar in Promoting Cancer Development and Progression. ANNUAL REVIEW OF CANCER BIOLOGY-SERIES 2019. [DOI: 10.1146/annurev-cancerbio-030518-055855] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The uncontrolled cellular growth that characterizes tumor formation requires a constant delivery of nutrients. Since the 1970s, researchers have wondered if the supply of nutrients from the diet could impact tumor development. Numerous studies have assessed the impact of dietary components, specifically sugar and fat, to increased cancer risk. For the most part, data from these trials have been inconclusive; however, this does not indicate that dietary factors do not contribute to cancer progression. Rather, the dietary contribution may be dependent on tumor, patient, and context, making it difficult to detect in the setting of large trials. In this review, we combine data from prospective cohort trials with mechanistic studies in mice to argue that fat and sugar can play a role in tumorigenesis and disease progression. We find that certain tumors may respond directly to dietary sugar (colorectal and endometrial cancers) and fat (prostate cancer) or indirectly to the obese state (breast cancer).
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Affiliation(s)
- Marcus D. Goncalves
- Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA;, ,
- Division of Endocrinology, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA
| | - Benjamin D. Hopkins
- Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA;, ,
| | - Lewis C. Cantley
- Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA;, ,
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Kim M, Park K. Dietary Fat Intake and Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Studies. Nutrients 2018; 10:nu10121963. [PMID: 30545042 PMCID: PMC6315498 DOI: 10.3390/nu10121963] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 12/07/2018] [Accepted: 12/10/2018] [Indexed: 12/11/2022] Open
Abstract
Dietary fat intake is associated with the risk of colorectal cancer (CRC); however, the results of epidemiological studies on this are controversial. Therefore, this study aimed to summarize the available scientific evidence regarding the association between dietary fat and the risk of CRC. We conducted a systematic search of PubMed, Web of Science, and the Cochrane library for articles related to dietary fat and the risk of CRC. The summary relative risks with 95% confidence intervals (CI) were calculated via a random effect model. Begg’s test was used to detect publication bias. A total of 18 articles were identified. The pooled relative risk with 95% CI for the risk of CRC were 1.00 (95% CI: 0.90–1.12), 0.97 (95% CI: 0.86–1.10), 1.08 (95% CI: 0.92–1.26), and 0.99 (95% CI: 0.93–1.04) for total fat, saturated fatty acid, monounsaturated fatty acid, and polyunsaturated fatty acid, respectively. No significant associations were found in subgroup analyses. Begg’s test for all exposures revealed no publication bias (total fat, p = 0.3; saturated fatty acid, p = 0.1; monounsaturated fatty acid, p = 0.08; polyunsaturated fatty acid, p = 0.2). The studies included in this review and meta-analysis revealed that dietary fats and fatty acids had no effects on the risk of CRC.
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Affiliation(s)
- Minkyeong Kim
- Department of Food and Nutrition, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
| | - Kyong Park
- Department of Food and Nutrition, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
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Abstract
Phospholipids are major constituents of biological membranes. The fatty acyl chain composition of phospholipids determines the biophysical properties of membranes and thereby affects their impact on biological processes. The composition of fatty acyl chains is also actively regulated through a deacylation and reacylation pathway called Lands' cycle. Recent studies of mouse genetic models have demonstrated that lysophosphatidylcholine acyltransferases (LPCATs), which catalyze the incorporation of fatty acyl chains into the sn-2 site of phosphatidylcholine, play important roles in pathophysiology. Two LPCAT family members, LPCAT1 and LPCAT3, have been particularly well studied. LPCAT1 is crucial for proper lung function due to its role in pulmonary surfactant biosynthesis. LPCAT3 maintains systemic lipid homeostasis by regulating lipid absorption in intestine, lipoprotein secretion, and de novo lipogenesis in liver. Mounting evidence also suggests that changes in LPCAT activity may be potentially involved in pathological conditions, including nonalcoholic fatty liver disease, atherosclerosis, viral infections, and cancer. Pharmacological manipulation of LPCAT activity and membrane phospholipid composition may provide new therapeutic options for these conditions.
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Affiliation(s)
- Bo Wang
- Department of Pathology and Laboratory Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, California 90272, USA;
| | - Peter Tontonoz
- Department of Pathology and Laboratory Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, California 90272, USA;
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Yang J, Yu J. The association of diet, gut microbiota and colorectal cancer: what we eat may imply what we get. Protein Cell 2018; 9:474-487. [PMID: 29713943 PMCID: PMC5960467 DOI: 10.1007/s13238-018-0543-6] [Citation(s) in RCA: 198] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 04/10/2018] [Indexed: 12/15/2022] Open
Abstract
Despite the success of colonoscopy screening and recent advances in cancer treatment, colorectal cancer (CRC) still remains one of the most commonly diagnosed and deadly cancers, with a significantly increased incidence in developing countries where people are adapting to Western lifestyle. Diet has an important impact on risk of CRC. Multiple epidemiological studies have suggested that excessive animal protein and fat intake, especially red meat and processed meat, could increase the risk of developing CRC while fiber could protect against colorectal tumorigenesis. Mechanisms have been investigated by animal studies. Diet could re-shape the community structure of gut microbiota and influence its function by modulating the production of metabolites. Butyrate, one of the short-chain fatty acids (SCFAs), which act as a favorable source for colonocytes, could protect colonic epithelial cells from tumorigenesis via anti-inflammatory and antineoplastic properties through cell metabolism, microbiota homeostasis, antiproliferative, immunomodulatory and genetic/epigenetic regulation ways. In contrast, protein fermentation and bile acid deconjugation, which cause damage to colonic cells through proinflammatory and proneoplastic ways, lead to increased risk of developing CRC. In conclusion, a balanced diet with an increased abundance of fiber should be adopted to reduce the risk and prevent CRC.
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Affiliation(s)
- Jia Yang
- State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jun Yu
- State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
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Fuentes NR, Kim E, Fan YY, Chapkin RS. Omega-3 fatty acids, membrane remodeling and cancer prevention. Mol Aspects Med 2018; 64:79-91. [PMID: 29627343 DOI: 10.1016/j.mam.2018.04.001] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 03/27/2018] [Accepted: 04/04/2018] [Indexed: 12/20/2022]
Abstract
Proteins are often credited as the macromolecule responsible for performing critical cellular functions, however lipids have recently garnered more attention as our understanding of their role in cell function and human health becomes more apparent. Although cellular membranes are the lipid environment in which many proteins function, it is now apparent that protein and lipid assemblies can be organized to form distinct micro- or nanodomains that facilitate signaling events. Indeed, it is now appreciated that cellular function is partly regulated by the specific spatiotemporal lipid composition of the membrane, down to the nanosecond and nanometer scale. Furthermore, membrane composition is altered during human disease processes such as cancer and obesity. For example, an increased rate of lipid/cholesterol synthesis in cancerous tissues has long been recognized as an important aspect of the rewired metabolism of transformed cells. However, the contribution of lipids/cholesterol to cellular function in disease models is not yet fully understood. Furthermore, an important consideration in regard to human health is that diet is a major modulator of cell membrane composition. This can occur directly through incorporation of membrane substrates, such as fatty acids, e.g., n-3 polyunsaturated fatty acids (n-3 PUFA) and cholesterol. In this review, we describe scenarios in which changes in membrane composition impact human health. Particular focus is placed on the importance of intrinsic lipid/cholesterol biosynthesis and metabolism and extrinsic dietary modification in cancer and its effect on plasma membrane properties.
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Affiliation(s)
- Natividad R Fuentes
- Program in Integrative Nutrition & Complex Diseases, Texas A&M University, USA; Faculty of Toxicology, Texas A&M University, USA
| | - Eunjoo Kim
- Program in Integrative Nutrition & Complex Diseases, Texas A&M University, USA; Department of Molecular and Cellular Medicine, Texas A&M University, USA
| | - Yang-Yi Fan
- Program in Integrative Nutrition & Complex Diseases, Texas A&M University, USA; Department of Nutrition & Food Science, Texas A&M University, USA
| | - Robert S Chapkin
- Program in Integrative Nutrition & Complex Diseases, Texas A&M University, USA; Faculty of Toxicology, Texas A&M University, USA; Department of Nutrition & Food Science, Texas A&M University, USA; Center for Translational Environmental Health Research, Texas A&M University, USA.
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Wang B, Rong X, Palladino END, Wang J, Fogelman AM, Martín MG, Alrefai WA, Ford DA, Tontonoz P. Phospholipid Remodeling and Cholesterol Availability Regulate Intestinal Stemness and Tumorigenesis. Cell Stem Cell 2018; 22:206-220.e4. [PMID: 29395055 PMCID: PMC5807072 DOI: 10.1016/j.stem.2017.12.017] [Citation(s) in RCA: 220] [Impact Index Per Article: 31.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 10/31/2017] [Accepted: 12/20/2017] [Indexed: 02/02/2023]
Abstract
Adequate availability of cellular building blocks, including lipids, is a prerequisite for cellular proliferation, but excess dietary lipids are linked to increased cancer risk. Despite these connections, specific regulatory relationships between membrane composition, intestinal stem cell (ISC) proliferation, and tumorigenesis are unclear. We reveal an unexpected link between membrane phospholipid remodeling and cholesterol biosynthesis and demonstrate that cholesterol itself acts as a mitogen for ISCs. Inhibition of the phospholipid-remodeling enzyme Lpcat3 increases membrane saturation and stimulates cholesterol biosynthesis, thereby driving ISC proliferation. Pharmacologic inhibition of cholesterol synthesis normalizes crypt hyperproliferation in Lpcat3-deficient organoids and mice. Conversely, increasing cellular cholesterol content stimulates crypt organoid growth, and providing excess dietary cholesterol or driving endogenous cholesterol synthesis through SREBP-2 expression promotes ISC proliferation in vivo. Finally, disruption of Lpcat3-dependent phospholipid and cholesterol homeostasis dramatically enhances tumor formation in Apcmin mice. These findings identify a critical dietary-responsive phospholipid-cholesterol axis regulating ISC proliferation and tumorigenesis.
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Affiliation(s)
- Bo Wang
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Xin Rong
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Elisa N D Palladino
- Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, Saint Louis University, St. Louis, MO, USA
| | - Jiafang Wang
- Department of Pediatrics, Division of Gastroenterology and Nutrition, Mattel Children's Hospital, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Alan M Fogelman
- Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Martín G Martín
- Department of Pediatrics, Division of Gastroenterology and Nutrition, Mattel Children's Hospital, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Waddah A Alrefai
- Research and Development, Jesse Brown VA Medical Center, Chicago, IL, USA; Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - David A Ford
- Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, Saint Louis University, St. Louis, MO, USA
| | - Peter Tontonoz
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
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Kaindi DWM, Kogi-Makau W, Lule GN, Kreikemeyer B, Renault P, Bonfoh B, Schelling E, Zinsstag J, Lacroix C, Meile L, Jans C, Hattendorf J. Investigating the association between African spontaneously fermented dairy products, faecal carriage of Streptococcus infantarius subsp. infantarius and colorectal adenocarcinoma in Kenya. Acta Trop 2018; 178:10-18. [PMID: 29079186 PMCID: PMC5766739 DOI: 10.1016/j.actatropica.2017.10.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 10/18/2017] [Accepted: 10/22/2017] [Indexed: 12/22/2022]
Abstract
Consumption of traditional fermented dairy products (tFDP) in Africa leads to the ingestion of up to 108Streptococcus infantarius subspecies infantarius (Sii) per millilitre of spontaneously fermented milk. Sii is a member of the Streptococcus bovis/Streptococcus equinus complex (SBSEC) for which some members are associated particularly with colorectal cancer or endocarditis. The extent of health risks to tFDP consumers is largely unknown. A hospital-based unmatched case-control study was conducted at Kenyatta National Hospital, Nairobi (Kenya) on 80 cases and 193 controls that were selected exhaustively from patients attending colonoscopy at the hospital. Logistic regression models adjusted for age, sex and residency were used in the statistical analysis. Consumption of tFDP was not associated with CRC (odds ratio (OR) 1.4; 95% Confidence interval (CI) 0.7-2.7; p=0.34). Risk factors associated with CRC included age above 40 years, and consumption of processed meat and alcohol. Faecal carriage of Sii was significantly higher in persons with colon tumours and polyps compared to controls (8.4% vs 21.6%: OR: 4.6; CI 1.3-15.9). Patients with haemorrhoids represented an unexpected carrier group with significantly higher Sii faecal carriage (30.4%, CI: 17.7-45.8). Consumption of tFDP does not represent risk factors for CRC whereas Sii seems to be associated with CRC. However, there is urgent need to assess this finding also in the general population, investigate the causality of SBSEC, Sii and CRC as well as compare the phylogenetic, functional and genomic relationship between human and dairy Sii with regards to the ongoing application of Sii in FDP production.
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Affiliation(s)
- Dasel W M Kaindi
- Department of Food Science, Nutrition and Technology, University of Nairobi, P. O. Box 29053 - 00625, Nairobi, Kenya.
| | - Wambui Kogi-Makau
- Department of Food Science, Nutrition and Technology, University of Nairobi, P. O. Box 29053 - 00625, Nairobi, Kenya.
| | - Godfrey N Lule
- School of Medicine, University of Nairobi, P. O. Box 19676, Nairobi, Kenya.
| | - Bernd Kreikemeyer
- Institute of Medical Microbiology, Virology, Hygiene and Bacteriology, Rostock University Medical Center Rostock, Schillingallee 70, 18055 Rostock, Germany.
| | - Pierre Renault
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
| | - Bassirou Bonfoh
- Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS), Km 17, Adiopodoumé, Rte Dabou, 01 BP 1303 Abidjan 01, Cote d'Ivoire; Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
| | - Esther Schelling
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
| | - Jakob Zinsstag
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
| | - Christophe Lacroix
- Laboratory of Food Biotechnology, Institute of Food Nutrition and Health, Department of Health Science and Technology, ETH Zurich, LFV C22, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.
| | - Leo Meile
- Laboratory of Food Biotechnology, Institute of Food Nutrition and Health, Department of Health Science and Technology, ETH Zurich, LFV C22, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.
| | - Christoph Jans
- Laboratory of Food Biotechnology, Institute of Food Nutrition and Health, Department of Health Science and Technology, ETH Zurich, LFV C22, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.
| | - Jan Hattendorf
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
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Abstract
OPINION STATEMENT Colorectal cancer (CRC) is the third most common cancer worldwide. CRC has been thought to be less common in Asia compared to Western countries. However, the incidence rates of CRC in Asia are high and there is an increasing trend in the Asian population. Furthermore, colorectal cancer accounts for the greatest number of all incidences of CRC in Asia. The increasing adoption of a Western lifestyle, particularly in dietary habits, is likely the most important factor contributing to the rapid increase in colon cancer incidence; it is noteworthy that trends for rectal cancer were flat. The etiology of colon and rectal cancer is a bit different. The risks of distal colon and rectal cancers are more likely to be related to environmental factors, such as polluted surface water sources, alcohol consumption, and habitual smoking. The lack of great change in the incidence of rectal cancer might be due to weaker associations with such lifestyle factors. Therefore, it has been hypothesized that proximal and distal sections of the colon and rectum are two different organs in terms of function and genetic background. It may mean differences in differential sensitivities and exposures to carcinogens. However, despite the decrease in whole incidence, the CRC incidence in young adults in Western countries are reversely increasing, especially in rectal cancer, due to reasons largely unknown. Although the treatment algorithm is different between Asia and western countries, globally, the survival rate for patients with rectal cancer has risen during the past 10 years. Screening contributes a great deal to reducing the incidence and improving survival. Most countries in Asia, such as China, need nationwide registration and screening systems to provide better data.
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Affiliation(s)
- Yanhong Deng
- Department of Medical Oncology, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Supported by National Key Clinical Discipline, The Sixth Affiliated Hospital, Sun Yat-sen University , 26 Yuancun Er Heng Road, Guangzhou, 510655, China.
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Momenyan S, Ghalane S, Sarvi F, Azizi R, Kabiri F. The Association between Lifestyle, Occupational, and Reproductive Factors and Colorectal Cancer Risk. Asian Pac J Cancer Prev 2017; 18:2157-2162. [PMID: 28843250 PMCID: PMC5697475 DOI: 10.22034/apjcp.2017.18.8.2157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Objective: Association of lifestyle, reproductive and environmental factors has been investigated with increased risk of colorectal cancer in different studies. We explored evidence and investigated association between various risk factors and colorectal cancer. Methods: This case- control study was conducted 155 colorectal cancer patients and 150 hospital-controls. We obtained detailed lifestyle, occupational, reproductive information from both groups. Chi-Square test and Logistic regression model were used to evaluate the risk factors of colorectal cancer. Results: The results showed that frequent intake of fruits, chicken, fish and alcohol drinking were associated with risk for colorectal cancer. Agricultural occupation (OR=7.003, 95% CI=2.19-22.38) and industrial exposure (OR=1.97, 95% CI=0.91-4.22) were associated significantly with risk for colorectal cancer. Regarding reproductive factors, women who reported less than 3 pregnancies was associated with an increased risk of colorectal carcinoma (OR=2.88, 95% CI=1.15-7.17). We did not find significant association between other reproductive factors and colorectal cancer risk in women after adjusting for demographic factors. Conclusion: In this case-control study we observed that agricultural occupation, industrial exposure and high consumption of fish and less than 3 pregnancies in women were associated with an increased risk of colorectal carcinoma.
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Affiliation(s)
- Somayeh Momenyan
- Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Bile acids and colon cancer: Is FXR the solution of the conundrum? Mol Aspects Med 2017; 56:66-74. [DOI: 10.1016/j.mam.2017.04.002] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 03/20/2017] [Accepted: 04/07/2017] [Indexed: 02/07/2023]
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Sharma I, Zhu Y, Woodrow JR, Mulay S, Parfrey PS, Mclaughlin JR, Hebert JR, Shivappa N, Li Y, Zhou X, Wang PP. Inflammatory diet and risk for colorectal cancer: A population-based case-control study in Newfoundland, Canada. Nutrition 2017; 42:69-74. [PMID: 28870481 DOI: 10.1016/j.nut.2017.05.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 05/08/2017] [Accepted: 05/17/2017] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Chronic inflammation is implicated in causing cancer. Diet plays an important role in regulating chronic inflammation by altering circulating levels of inflammatory biomarkers. Effect of single food or nutrient on cancer often is inconclusive; perhaps due to dietary interactions and multicolinearity. The aim of this study was to determine prediagnostic inflammatory potential of overall diet in relation to risk for colorectal cancer (CRC). METHODS In all, 547 patients with CRC from Newfoundland Familial Colorectal Cancer Registry and 685 controls from the general population were identified. Data on sociodemographic, medical history, lifestyle, and a 169-item food frequency questionnaire were collected retrospectively from both groups. Energy-adjusted Dietary Inflammatory Index (DII) score was calculated and used as both categorical and continuous variables for analysis. Odds ratio was estimated using multivariable logistic regression after adjusting potential confounders. A linear test for trend was performed using the median value in each quartile. RESULTS Overall energy-adjusted mean DII score was -0.81 (range -5.19 to 6.93). Cases (-0.73 ± 1.5) had slightly higher DII scores than controls (-0.89 ± 1.6; P = 0.04). After adjusting the potential confounders, a statistically significant association was found between DII score and CRC risk. Using DII as a continuous variable (odds ratio [OR]continuous 1.10, 95% confidence interval [CI] 1.01-1.20) and categorical variable (ORquartile 1 versus 4 1.65, 95% CI 1.13-2.42; Ptrend = 0.02). CONCLUSION Our findings indicate that proinflammatory diets are associated with an increased risk for CRC in the Newfoundland population.
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Affiliation(s)
- Ishor Sharma
- Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | - Yun Zhu
- Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | - Jennifer R Woodrow
- Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | - Shree Mulay
- Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | - Patrick S Parfrey
- Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | | | - James R Hebert
- Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina, USA; Cancer Prevention and Control Program, University of South Carolina, Columbia, South Carolina, USA
| | - Nitin Shivappa
- Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina, USA; Cancer Prevention and Control Program, University of South Carolina, Columbia, South Carolina, USA
| | - Yuming Li
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of Chinese People's Armed Police Force, Tianjin, China
| | - Xin Zhou
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of Chinese People's Armed Police Force, Tianjin, China
| | - Peizhong Peter Wang
- Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Abstract
A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trend<0·01) for total phytosterols. An inverse association was also found between the consumption of β-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.
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Das V, Kalita J, Pal M. Predictive and prognostic biomarkers in colorectal cancer: A systematic review of recent advances and challenges. Biomed Pharmacother 2016; 87:8-19. [PMID: 28040600 DOI: 10.1016/j.biopha.2016.12.064] [Citation(s) in RCA: 178] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 12/15/2016] [Accepted: 12/15/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. Since CRC is largely asymptomatic until alarm features develop to advanced stages, the implementation of the screening programme is very much essential to reduce cancer incidence and mortality rates. CRC occurs predominantly from accumulation of genetic and epigenetic changes in colon epithelial cells, which later gets transformed into adenocarcinomas. SCOPE OF REVIEW The current challenges of screening paradigm and diagnostic ranges are from semi-invasive methods like colonoscopy to non-invasive stool-based test, have resulted in over-diagnosis and over-treatment of CRC. Hence, new screening initiatives and deep studies are required for early diagnosis of CRC. In this regard, we not only summarise current predictive and prognostic biomarkers with their potential for diagnostic and therapeutic applications, but also describe current limitations, future perspectives and challenges associated with the progression of CRC. MAJOR CONCLUSIONS Currently many potential biomarkers have already been successfully translated into clinical practice eg. Fecal haemoglobin, Carcinoembryonic antigen (CEA) and CA19.9, although these are not highly promising diagnostic target for personalized medicine. So there is a critical need for reliable, minimally invasive, highly sensitive and specific genetic markers of an individualised and optimised patient treatment at the earliest disease stage possible. GENERAL SIGNIFICANCE Identification of a new biomarker, or a set of biomarkers to the development of a valid, and clinical sensible assay that can be served as an alternative tool for early diagnosis of CRC and open up promising new targets in therapeutic intervention strategies.
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Affiliation(s)
- Vishal Das
- Biotechnology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India
| | - Jatin Kalita
- Biotechnology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India
| | - Mintu Pal
- Biotechnology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India.
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Fiorentino M, Landais E, Bastard G, Carriquiry A, Wieringa FT, Berger J. Nutrient Intake Is Insufficient among Senegalese Urban School Children and Adolescents: Results from Two 24 h Recalls in State Primary Schools in Dakar. Nutrients 2016; 8:E650. [PMID: 27775598 PMCID: PMC5084037 DOI: 10.3390/nu8100650] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 09/05/2016] [Accepted: 10/14/2016] [Indexed: 11/16/2022] Open
Abstract
Due to rapid urbanization and high food prices and in the absence of nutrition programs, school children from urban areas in West Africa often have insufficient and inadequate diet leading to nutrient deficiencies that affect their health and schooling performance. Acute malnutrition and micronutrient deficiencies are prevalent in children from primary state schools of Dakar (Senegal). The objectives of the present study were to assess the overall diet of these children, to report insufficient/excessive energy and nutrient intakes and to investigate association between insufficient nutrient intake and micronutrient deficiencies. Children attending urban state primary schools in the Dakar area were selected through a two-stage random cluster sampling (30 schools × 20 children). Dietary intake data were obtained from two 24 h recalls and blood samples were collected from 545 children (aged 5-17 years, 45% < 10 years, 53% girls) and adjusted for intra-individual variability to estimate nutrient usual intakes. Energy intake was insufficient and unbalanced with insufficient contribution of protein and excessive contribution of fat to global energy intake in one third of the children. Proportions of children with insufficient intake were: 100% for calcium, 100% for folic acid, 79% for vitamin A, 69% for zinc, 53% for vitamin C and 46% for iron. Insufficient iron and protein intake were risk factors for iron deficiency (odds ratio, OR 1.5, 2.2). Insufficient zinc intake and energy intake from protein were risk factors for zinc deficiency (OR 1.8, 3.0, 1.7, 2.9). Insufficient iron and vitamin C intake, and insufficient energy intake from protein were risk factors for marginal vitamin A status (OR 1.8, 1.8, 3.3). To address nutritional deficiencies associated with a diet deficient in energy, protein and micronutrients, nutrition education or school feeding programs are needed in urban primary schools of Senegal.
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Affiliation(s)
- Marion Fiorentino
- UMR 204 Nutripass IRD-UM-SupAgro, Institut de Recherche pour le Développement, 911 Avenue d'Agropolis, Montpellier 34394, France.
| | - Edwige Landais
- UMR 204 Nutripass IRD-UM-SupAgro, Institut de Recherche pour le Développement, 911 Avenue d'Agropolis, Montpellier 34394, France.
| | | | - Alicia Carriquiry
- Department of Statistics, Iowa State University, Ames, IA 50011, USA.
| | - Frank T Wieringa
- UMR 204 Nutripass IRD-UM-SupAgro, Institut de Recherche pour le Développement, 911 Avenue d'Agropolis, Montpellier 34394, France.
| | - Jacques Berger
- UMR 204 Nutripass IRD-UM-SupAgro, Institut de Recherche pour le Développement, 911 Avenue d'Agropolis, Montpellier 34394, France.
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Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. Understanding its pathophysiology is essential for developing efficient strategies to treat this disease. Lipidome, the sum of total lipids, related enzymes, receptors and signaling pathways, plays crucial roles in multiple cellular processes, such as metabolism, energy storage, proliferation and apoptosis. Dysregulation of lipid metabolism and function contributes to the development of CRC, and can be used towards the evaluation of prognosis. The strategies targeting lipidome have been applied in clinical trails and showed promising results. Here we discuss recent advances in abnormal lipid metabolism in CRC, the mechanisms by which the lipidome regulates tumorigenesis and tumor progression, and suggest potential therapeutic targets for clinical trials.
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Affiliation(s)
- Guifang Yan
- Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Liqi Li
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Bo Zhu
- Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yongsheng Li
- Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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Sehdev A, O'Neil BH. The Role of Aspirin, Vitamin D, Exercise, Diet, Statins, and Metformin in the Prevention and Treatment of Colorectal Cancer. Curr Treat Options Oncol 2016; 16:43. [PMID: 26187794 DOI: 10.1007/s11864-015-0359-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Colorectal cancer (CRC) is a worldwide health problem leading to significant morbidity and mortality. Several strategies based on either lifestyle modifications or pharmacological interventions have been developed in an attempt to reduce the risk of CRC. In this review article, we discuss these interventions including aspirin (and other non-steroidal anti-inflammatory drugs), vitamin D, exercise, diet, statins, and metformin. Depending upon the risk of developing CRC, the current evidence supports the beneficial role of aspirin, vitamin D, diet, and exercise especially in high-risk individuals (advanced adenoma or CRC). However, even with these established interventions, there are significant knowledge gaps such as doses of aspirin and 25-hydroxy vitamin D are not well established. Similarly, there is no convincing data from randomized controlled trials that a high fiber diet or a low animal fat diet reduces the risk of CRC. Some potential interventions, such as statins and metformin, do not have convincing data for clinical use even in high-risk individuals. However, these may have emerging roles in the prevention and treatment of CRC. Greater understanding of molecular mechanisms and the application of genomic tools to risk stratify an individual and tailor the interventions based on that individual's risk will help further advance the field. Some of this work is already underway and is a focus of this article.
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Affiliation(s)
- Amikar Sehdev
- Division of Hematology Oncology, Department of Medicine, Indiana University, 535 Barnhill Dr., RT 130B, Indianapolis, IN, 46202, USA,
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Kuzu OF, Noory MA, Robertson GP. The Role of Cholesterol in Cancer. Cancer Res 2016; 76:2063-70. [PMID: 27197250 DOI: 10.1158/0008-5472.can-15-2613] [Citation(s) in RCA: 478] [Impact Index Per Article: 53.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 02/08/2016] [Indexed: 12/19/2022]
Abstract
The roles played by cholesterol in cancer development and the potential of therapeutically targeting cholesterol homeostasis is a controversial area in the cancer community. Several epidemiologic studies report an association between cancer and serum cholesterol levels or statin use, while others suggest that there is not one. Furthermore, the Cancer Genome Atlas (TCGA) project using next-generation sequencing has profiled the mutational status and expression levels of all the genes in diverse cancers, including those involved in cholesterol metabolism, providing correlative support for a role of the cholesterol pathway in cancer development. Finally, preclinical studies tend to more consistently support the role of cholesterol in cancer, with several demonstrating that cholesterol homeostasis genes can modulate development. Because of space limitations, this review provides selected examples of the epidemiologic, TCGA, and preclinical data, focusing on alterations in cholesterol homeostasis and its consequent effect on patient survival. In melanoma, this focused analysis demonstrated that enhanced expression of cholesterol synthesis genes was associated with decreased patient survival. Collectively, the studies in melanoma and other cancer types suggested a potential role of disrupted cholesterol homeostasis in cancer development but additional studies are needed to link population-based epidemiological data, the TCGA database results, and preclinical mechanistic evidence to concretely resolve this controversy. Cancer Res; 76(8); 2063-70. ©2016 AACR.
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Affiliation(s)
- Omer F Kuzu
- Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
| | - Mohammad A Noory
- Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
| | - Gavin P Robertson
- Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Penn State Hershey Melanoma Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Penn State Melanoma Therapeutics Program, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. The Foreman Foundation for Melanoma Research, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
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BI DAPENG, YIN CHENGHUA, ZHANG XIAOYUE, YANG NANA, XU JIAYOU. miR-183 functions as an oncogene by targeting ABCA1 in colon cancer. Oncol Rep 2016; 35:2873-9. [DOI: 10.3892/or.2016.4631] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2015] [Accepted: 10/13/2015] [Indexed: 11/05/2022] Open
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