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Swerdlow AJ, Jones ME, Slater SD, Burden ACF, Botha JL, Waugh NR, Morris AD, Gatling W, Gillespie KM, Patterson CC, Schoemaker MJ. Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up. Int J Cancer 2023; 153:512-523. [PMID: 37190903 PMCID: PMC10952206 DOI: 10.1002/ijc.34548] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 03/21/2023] [Accepted: 04/03/2023] [Indexed: 05/17/2023]
Abstract
Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.
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Affiliation(s)
- Anthony J. Swerdlow
- Division of Genetics and EpidemiologyThe Institute of Cancer ResearchLondonUK
- Division of Breast Cancer ResearchThe Institute of Cancer ResearchLondonUK
| | - Michael E. Jones
- Division of Genetics and EpidemiologyThe Institute of Cancer ResearchLondonUK
| | | | | | | | | | | | - Wendy Gatling
- Department of DiabetesPoole Hospital NHS TrustDorsetUK
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Yan P, Wang Y, Yu X, Liu Y, Zhang ZJ. Type 2 diabetes mellitus and risk of head and neck cancer subtypes: a systematic review and meta-analysis of observational studies. Acta Diabetol 2021; 58:549-565. [PMID: 33389127 DOI: 10.1007/s00592-020-01643-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 11/20/2020] [Indexed: 02/06/2023]
Abstract
AIMS The association between type 2 diabetes mellitus (T2DM) and risk of head and neck cancer (HNC) remains unclear. This study aims to perform a system review and meta-analysis to explore this relationship. METHODS PubMed, Web of Science, and Embase databases were searched for studies published up to July 31, 2020, regarding the association between T2DM and HNC risk. A random-effects model was utilized to calculate summary relative risks (RRs) with corresponding 95% confidence intervals (CIs). RESULTS Fourteen case-control studies and thirteen cohort studies were included in our analysis. We observed a weak association between T2DM and risk of HNC overall, but there was no statistical significance (RR, 1.04; 95% CI, 0.88-1.23; I2 = 83.2%). Interestingly, there was a strong association in East Asia (RR, 1.46; 95% CI, 1.21-1.77; I2 = 36.6%). For HNC subtypes, T2DM conferred a significantly elevated risk in oral cancer (RR, 1.22; 95% CI, 1.01-1.47; I2 = 89.0%). However, in subgroup analyses of smoking, alcohol use, and body mass index (BMI)/obesity adjustments, the association between T2DM and oral cancer risk became insignificant. In addition, T2DM was not associated with a statistically elevated risk of pharyngeal cancer (RR, 1.18; 95% CI, 0.94-1.49; I2 = 72.9%) and laryngeal cancer (RR, 1.03; 95% CI, 0.88-1.22; I2 = 71.2%). CONCLUSIONS This meta-analysis indicates that T2DM is associated with an increased risk of HNC in East Asia. As for site-specific cancer types, the risk of oral cancer was significantly increased in T2DM patients, which appear to be mediated or confounded by smoking, alcohol use, or BMI/obesity.
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Affiliation(s)
- Pengfei Yan
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China
| | - Yongbo Wang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Xue Yu
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China
| | - Yu Liu
- Department of Statistics and Management, School of Management, Wuhan Institute of Technology, Wuhan, 430205, China
| | - Zhi-Jiang Zhang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China.
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Yang Q, Ouyang J, Sun F, Yang J. Short-Chain Fatty Acids: A Soldier Fighting Against Inflammation and Protecting From Tumorigenesis in People With Diabetes. Front Immunol 2020; 11:590685. [PMID: 33363537 PMCID: PMC7752775 DOI: 10.3389/fimmu.2020.590685] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 11/03/2020] [Indexed: 12/16/2022] Open
Abstract
Converging evidences showed that people with diabetes mellitus (DM) have significantly higher risk for different cancers, of which the exact mechanism underlying the association has not been fully realized. Short-chain fatty acids (SCFAs), the fermentation products of the intestinal microbiota, are an essential source for energy supply in gut epithelial cells. They have been reported to improve intestinal barrier integrity, prevent microbial translocation, and further dampen inflammation. Gut dysbiosis and reduction in SCFA-producing bacteria as well as SCFAs production in the intestine are commonly seen in metabolic disorders including DM and obesity. Moreover, inflammation can contribute to tumor initiation and progression through multiple pathways, such as enhancing DNA damage, accumulating mutations in tumor suppressor genes Tp53, and activating nuclear factor-kappa B (NF-κB) signaling pathways. Based on these facts, we hypothesize that lower levels of microbial SCFAs resulted from gut dysbiosis in diabetic individuals, enhance microbial translocation, and increase the inflammatory responses, inducing tumorigenesis ulteriorly. To this end, we will discuss protective properties of microbial SCFAs and explore the pivotal roles SCFAs played in the link of DM with cancer, so as to take early precautions to reduce the risk of cancer in patients with DM.
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Affiliation(s)
- Qiyu Yang
- Department of Radiation Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Hospital, Chongqing, China
| | - Jing Ouyang
- Chongqing Public Health Medical Center, Chongqing, China
| | - Fengjun Sun
- Department of Pharmacy, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, China
| | - Jiadan Yang
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Diabetes mellitus in intraductal papillary mucinous neoplasms: A systematic review and meta-analysis. Surgery 2020; 169:411-418. [PMID: 32838986 DOI: 10.1016/j.surg.2020.07.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 06/07/2020] [Accepted: 07/03/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Our current knowledge of diabetes mellitus in intraductal papillary mucinous neoplasm is very limited and its prevalence and predictive value for malignant transformation are not clear. This study sought to systematically review the literature to define the prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm and to evaluate the association of diabetes mellitus with the progression to high-grade dysplasia or invasive cancer. METHODS A PubMed/Medline systematic search was performed to identify studies reporting data on preoperative diabetes mellitus in intraductal papillary mucinous neoplasm. Articles meeting the predefined inclusion criteria were analyzed and a meta-analysis was performed. The study was preregistered (PROSPERO ID: CRD42020153581). RESULTS From the initially detected 827 studies, 27 studies including resected patients with histologically confirmed intraductal papillary mucinous neoplasm were included. The global prevalence of preoperative diabetes mellitus was 25% (1,112 of 4,412); whereas new-onset/worsening diabetes mellitus was reported in 6% of patients (68 of 1,202). The meta-analysis revealed that patients with pre-existing diabetes mellitus had an increased risk of harboring a main pancreatic duct involvement (risk ratio 1.43, 95% confidence interval: 1.21-1.69, P < .001), high-grade dysplasia (risk ratio 1.27, 95% confidence interval: 1.01-1.59, P = .04), and invasive cancer (risk ratio 1.61, 95% confidence interval: 1.33-1.95, P < .001). CONCLUSION The prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm is high, and diabetic patients demonstrate an increased risk of a more aggressive disease. Therefore, diabetes mellitus should be increasingly considered in the stratification of patients with intraductal papillary mucinous neoplasm. Further investigations to determine the mechanisms behind the association with progression should be carried out.
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Rashed WM, Kandeil MAM, Mahmoud MO, Ezzat S. Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview. J Egypt Natl Canc Inst 2020; 32:5. [PMID: 32372179 DOI: 10.1186/s43046-020-0016-x] [Citation(s) in RCA: 108] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/02/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Worldwide, hepatocellular carcinoma (HCC) is a universal problem and its epidemiological data showed variation from place to place. Hepatocellular carcinoma (HCC) is the sixth and fourth common cancer in worldwide and Egypt, respectively. Egypt ranks the third and 15th most populous country in Africa and worldwide, respectively. The aim of this review is to compare the status of HCC in Egypt to that in the worldwide from different issues; risk factors, screening and surveillance, diagnosis and treatment, prevention, as well as research strategy. MAIN BODY The risk factors for HCC in Egypt are of great importance to be reported. The risk factor for HCC are either environmental- or host/genetic-related risk factors. In the last years, there is a tangible improvement of both screening and surveillance strategies of HCC in Egypt. The unprecedented national screening campaign launched by the end of 2018 is a mirror image of this improvement. While the improvement of the HCC prevention requires the governmental health administration to implement health policies. Although the diagnosis of Egyptian HCC patients follows the international guidelines but HCC treatment options are limited in terms of cost. In addition, there are limited Egyptian reports about HCC survival and relapse. Both basic and clinical HCC research in Egypt are still limited compared to worldwide. SHORT CONCLUSION Deep analysis and understanding of factors affecting HCC burden variation worldwide help in customization of efforts exerted to face HCC in different countries especially large country like Egypt. Overall, the presence of a research strategy to fight HCC in Egyptian patients will help in the optimum allocation of available resources to reduce the numbers of HCC cases and deaths and to improve the quality of life.
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Affiliation(s)
- Wafaa M Rashed
- Department of Research, Children's Cancer Hospital-57357, Cairo, Egypt.
| | | | - Mohamed O Mahmoud
- Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Sameera Ezzat
- Department of Epidemiology and Prevention Medicine, National Liver Institute, Menoufia University, Menoufia, Egypt
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Abudawood M, Tabassum H, Almaarik B, Aljohi A. Interrelationship between oxidative stress, DNA damage and cancer risk in diabetes (Type 2) in Riyadh, KSA. Saudi J Biol Sci 2020; 27:177-183. [PMID: 31889833 PMCID: PMC6933234 DOI: 10.1016/j.sjbs.2019.06.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/10/2019] [Accepted: 06/23/2019] [Indexed: 12/20/2022] Open
Abstract
Type 2 Diabetes Mellitus (T2DM) is the most widely known type of disorder of the endocrine system marked by hyperglycemia resulting either due to deficiency of insulin and or resistance. Persistent hyperglycemia induces oxidative stress and is suggested to play a prominent role in the pathophysiology underlying T2DM. Besides, oxidative stress can result in DNA damage leading to high cancer risk. Current study aimed to evaluate status of oxidative damage, damage to DNA and cancer biomarkers in regard to increased glucose in T2DM patients and to correlate the glycemic state with cancer. A total of 150 subjects consisting of control (50) and T2DM patients (1 0 0) were enrolled. Additionally, three tertiles were created among the two groups based on levels of HbA1c (Tertile I = 5.37 ± 0.34, n = 50; Tertile II = 6.74 ± 0.20, n = 50; Tertile III = 9.21 ± 1.47, n = 50). Oxidative stress parameters including malondialedehyde (MDA) and antioxidant enzymes were measured. Damage to DNA was analyzed by measuring the levels of DNA damage adduct-8 hydroxy deoxy Guanosine (8-OHdG). To detect cancer resulting from oxidative stress, cancer biomarkers CEA, AFP, CA125, CA-15, CA19-9, prolactin were measured in these subjects. All measurements were analysed by SPSS software. Levels of MDA and antioxidant enzymes altered significantly in T2DM group at p < 0.001 and p < 0.05 level of significance. Significant DNA damage accompanied with elevated levels of CEA, CA19-9 and decreased CA125, AFP and prolactin were noted in T2DM group. CA 19-9 and CEA levels increased at p < 0.05, whereas levels of prolactin decreased significantly (p < 0.001) in T2DM group compared to control. Additionally the mean values of DNA damage adduct 8-OHdG differ significantly at P < 0.01 between the two groups. However, no significant correlation in oxidative stress parameter, antioxidant enzymes, DNA damage and neither with the highest tertile of HbA1c (>7.5%) was noted. Based on the results obtained in the present study, we conclude that there is considerable change in oxidative stress and DNA damage in T2DM patients. Hence, assumption that the oxidative stress could cause cancer in T2DM as a result of hyperglycemic state was not speculated in this study.
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Affiliation(s)
- Manal Abudawood
- Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Hajera Tabassum
- Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Basmah Almaarik
- Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ali Aljohi
- Central Military Laboratory & Blood Bank, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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Gao R, Man TS, Liang JH, Wang L, Zhu HY, Wu W, Fan L, Li JY, Yang T, Xu W. Diabetes Mellitus Is Associated with Inferior Prognosis in Patients with Chronic Lymphocytic Leukemia: A Propensity Score-Matched Analysis. Cancer Res Treat 2019; 52:189-206. [PMID: 31291713 PMCID: PMC6962470 DOI: 10.4143/crt.2019.122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 06/26/2019] [Indexed: 12/16/2022] Open
Abstract
Purpose Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL). Materials and Methods Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL–International Prognostic Index (IPI) together with DM. Results The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLL-IPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI. Conclusion Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.
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Affiliation(s)
- Rui Gao
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Tian-Shuo Man
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
| | - Jin-Hua Liang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
| | - Li Wang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
| | - Hua-Yuan Zhu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
| | - Wei Wu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
| | - Lei Fan
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
| | - Jian-Yong Li
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
| | - Tao Yang
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Wei Xu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
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Wang Y, Liu X, Yan P, Bi Y, Liu Y, Zhang ZJ. Association between type 1 and type 2 diabetes and risk of non-Hodgkin's lymphoma: A meta-analysis of cohort studies. DIABETES & METABOLISM 2019; 46:8-19. [PMID: 31039401 DOI: 10.1016/j.diabet.2019.04.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/12/2019] [Accepted: 04/14/2019] [Indexed: 12/14/2022]
Abstract
AIM Diabetes mellitus (DM) is thought to be associated with an increased risk of non-Hodgkin's lymphoma (NHL), although the evidence so far remains inconsistent. Thus, our study aimed to further assess this association. METHODS Electronic searches were performed of the PubMed, Web of Science and Embase databases up to 11 March 2019. A random-effects model was used to calculate summary relative risks (RRs) with corresponding 95% confidence intervals (CIs). RESULTS A total of 20 articles including data from 35 cohort studies matched our inclusion criteria, and 31 RRs were calculated for type 2 DM; the summary RR was 1.20 (95% CI: 1.12-1.30, I2 = 84.7%). Also, four RRs were calculated for type 1 DM, and the result was significant (RR: 1.55, 95% CI: 1.15-2.08, I2 = 0.0%). The results of subgroup analyses demonstrated that the association between DM and NHL was much more substantial in an Asian population, while sensitivity analyses suggested the robustness of a positive association between DM and NHL risk. In addition, the RR of NHL correlated negatively with duration of DM, with the highest risk found in patients within 1-2 years of DM diagnosis. CONCLUSION Our study findings suggest a moderate increase in risk of NHL in type 1 and 2 DM patients. Future studies should investigate the effects of duration of DM and antidiabetes interventions on NHL risk.
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Affiliation(s)
- Y Wang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - X Liu
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - P Yan
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - Y Bi
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China
| | - Y Liu
- Department of Statistics and Management, School of Management, Wuhan Institute of Technology, Wuhan, 430205, PR China
| | - Z-J Zhang
- Department of Preventive Medicine, School of Health Sciences, Wuhan University, No. 185 Donghu road, Wuhan 430071, PR China.
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Arthur R, Kabat GC, Kim MY, Ho GYF, Chlebowski RT, Pan K, Rohan TE. Adiposity, history of diabetes, and risk of pancreatic cancer in postmenopausal women. Ann Epidemiol 2018; 29:23-29.e1. [PMID: 30449532 DOI: 10.1016/j.annepidem.2018.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 09/05/2018] [Accepted: 09/12/2018] [Indexed: 11/29/2022]
Abstract
PURPOSE The purpose of this study was to examine the association of type II diabetes and anthropometric variables with risk of pancreatic cancer among postmenopausal women. METHODS Weight, height, waist circumference, and hip circumference were measured by trained personnel, whereas history of diabetes and weight earlier in life were self-reported. Pancreatic cancer was ascertained via central review of medical records by physician adjudicators. After exclusions, 1045 cases of pancreatic cancer were diagnosed among 156,218 women over a median follow-up of approximately 18 years. Cox proportional hazards models were used to estimate the associations of study factors with pancreatic cancer risk. RESULTS Diabetes (hazards ratio (HR): 1.30; 95% confidence intervals (95% CI): 1.01-1.66), and in particular, waist circumference, waist-to-hip ratio, and waist-to-height ratio showed positive associations with pancreatic cancer risk (HRs for highest vs. lowest level 1.38; 95% CI: 1.14-1.66, 1.40; 1.17-1.68; and 1.36; 1.13-1.64, respectively). Body mass index at the baseline showed only a borderline positive association with risk (HR: 1.21; 95% CI: 0.97-1.51). Body mass index at age 50 years, but not at ages 18 and 35 years, was also associated with increased pancreatic cancer risk. CONCLUSIONS In this study of postmenopausal women, central adiposity and, to a lesser extent, general adiposity and a history of diabetes, were associated with increased pancreatic cancer risk.
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Affiliation(s)
- Rhonda Arthur
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
| | | | - Mimi Y Kim
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | - Gloria Y F Ho
- Center for Health Innovations and Outcomes Research, Feinstein Institute for Medical Research, Northwell Health, Great Neck, NY
| | - Rowan T Chlebowski
- Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA
| | - Kathy Pan
- Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA; Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA
| | - Thomas E Rohan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
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Sona MF, Myung SK, Park K, Jargalsaikhan G. Type 1 diabetes mellitus and risk of cancer: a meta-analysis of observational studies. Jpn J Clin Oncol 2018; 48:426-433. [PMID: 29635473 DOI: 10.1093/jjco/hyy047] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 04/03/2018] [Indexed: 02/06/2023] Open
Abstract
Objective Previous observational studies have focused on the link between type 2 diabetes and the risk of cancer. However, the association between type 1 diabetes and the risk of cancer has not been well addressed. This study aimed to investigate the association between type 1 diabetes and the risk of cancer by using a meta-analysis of observational studies. Methods We searched PubMed and EMBASE for observational studies that examined the association between type 1 diabetes and cancer in April 2017. We calculated the pooled odds ratios (ORs) or relative risks (RRs) with confidence intervals (CIs) from individual studies based on a random-effects model meta-analysis. Results We included a total of 15 observational studies with two case-control studies and 13 cohort studies involving 31 893 cancer patients among a total of 1 915 179 participants in the final analysis. In the random-effects meta-analysis of all studies, patients with type 1 diabetes had an increased risk of cancer (OR or RR, 1.29; 95% CI, 1.09-1.52; n = 15; I2 = 95.2%). In the subgroup meta-analysis by type of cancer, type 1 diabetes significantly increased the risk of cancers of stomach, lung, pancreas, liver, ovary and kidney, whereas it significantly decreased the risk of breast cancer (OR or RR, 0.91; 95% CI, 0.86-0.95; n = 9; I2 = 0%). Conclusion This meta-analysis suggests that type 1 diabetes is associated with the increased risk of several types of cancer and the decreased risk of breast cancer. However, the plausible mechanisms for the decreased risk of breast cancer remain unclear. Further prospective studies with proper adjustment for possible confounding factors are warranted.
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Affiliation(s)
- Mukete Franklin Sona
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.,Regional Hospital Garoua, Ministry of Public Health, Garoua, Republic of Cameroon
| | - Seung-Kwon Myung
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy.,Cancer Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center.,Department of Family Medicine and Center for Cancer Prevention and Detection, Hospital, National Cancer Center, Goyang, Korea
| | - Keeho Park
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea
| | - Galsuren Jargalsaikhan
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.,School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
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Scotti L, Tavani A, Bosetti C, Maso LD, Talamini R, Montella M, Franceschi S, La Vecchia C. Diabetes and Risk of Non-Hodgkin Lymphoma: A Case-Control Study. TUMORI JOURNAL 2018; 93:1-3. [PMID: 17455863 DOI: 10.1177/030089160709300101] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Aims and background We investigated the relation between diabetes and the risk of non-Hodgkin lymphoma, as epidemiological results are controversial and diabetes has been related to the risk of several neoplasms. Patients and methods We analyzed the combined dataset of two Italian case-control studies conducted in 1985-1997 and 1999-2002. Cases were 671 patients, aged <85 years, with incident, histologically confirmed non-Hodgkin lymphoma, and controls were 1799 patients admitted to hospitals for acute non-neoplastic conditions. Odds ratios were estimated using unconditional multiple logistic regression models including terms for age, center, sex, residence and educational level. Results No material association between diabetes and non-Hodgkin lymphoma risk was observed, with an odds ratio of 1.12 (95% confidence intervals, 0.70-1.77). No association was found in relation to age at first diagnosis of diabetes, years since diagnosis, or in younger and older subjects at diagnosis of non-Hodgkin lymphoma. Conclusions The results of the study allow to exclude a strong association between diabetes and non-Hodgkin lymphoma, although the small number of cases with diabetes leaves open the possibility of a moderate direct relation.
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Affiliation(s)
- Lorenza Scotti
- Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
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Barami K, Lyon L, Conell C. Type 2 Diabetes Mellitus and Glioblastoma Multiforme-Assessing Risk and Survival: Results of a Large Retrospective Study and Systematic Review of the Literature. World Neurosurg 2017; 106:300-307. [PMID: 28698089 DOI: 10.1016/j.wneu.2017.06.164] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Revised: 06/27/2017] [Accepted: 06/29/2017] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Despite studies showing a positive correlation between type 2 diabetes mellitus (DM2), a modifiable risk factor, and various cancer types, the link remains controversial in the setting of glioblastoma multiforme (GBM). In this study, we assessed whether DM2 and DM2-associated factors were associated with a higher risk of developing GBM and also determined if DM2 affected the survival of patients with GBM. METHODS A cross-sectional case-control study of 1144 GBM cases diagnosed between 2000 and 2013 of which 969 patients matched for age and sex was performed to assess the association between DM2, hyperlipidemia, and obesity with the incidence of GBM. A longitudinal study of the patients with GBM was also performed to assess the association between the effect of DM2 and GBM survival. RESULTS No association was seen between DM2, hyperlipidemia, obesity, and GBM. DM2 was associated with poorer survival in univariate testing yet not in multivariate testing. Diabetic patients with GBM had good glycemic control. Older patients had poorer survival and overall survival improved over years of study. CONCLUSIONS DM2, hyperlipidemia, and obesity were not associated with increased risk of developing GBM, and DM2 itself does not seem to influence survival among these patients. This finding might be related to good glycemic control in this cohort. Survey of the literature consistently shows that hyperglycemia is associated with poorer survival. Our findings suggest that rather than the presence or absence of DM2, glycemic control seems to be more important in the survival of patients with GBM, which warrants future investigation.
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Affiliation(s)
- Kaveh Barami
- Department of Neurosurgery, Kaiser Permanente Northern California, Sacramento, California, USA.
| | - Liisa Lyon
- The Kaiser Permanente Northern California Division of Research, Oakland, California, USA
| | - Carol Conell
- The Kaiser Permanente Northern California Division of Research, Oakland, California, USA
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14
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Type 2 diabetes and the risk of non-Hodgkin's lymphoma: a report from two population-based cohort studies in China. Eur J Cancer Prev 2016; 25:149-54. [PMID: 25793918 DOI: 10.1097/cej.0000000000000150] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Coinciding with the increased incidence of non-Hodgkin's lymphoma (NHL) during the past decades, there has been a significant increase in the prevalence of diabetes mellitus in mainland China. We therefore evaluated whether type 2 diabetes (T2D) is associated with the risk of NHL using data from the Shanghai Men's Health Study (SMHS) and the Shanghai Women's Health Study (SWHS). The SMHS and SWHS are two on-going, prospective, population-based cohorts of more than 130 000 Chinese adults in urban Shanghai. Self-reported diabetes was recorded on the baseline questionnaire and updated in follow-up surveys. Cox regression models with T2D as a time-varying exposure were used to estimate hazard ratios and 95% confidence intervals, adjusting for covariates. After a median follow-up of 12.9 years for SWHS and 7.4 years for SMHS, 172 NHL cases were identified. Patients with T2D have a higher risk of incident NHL with a hazard ratio of 2.00 (95% confidence interval: 1.32-3.03) compared with those without diabetes. This positive association remained when the analysis was restricted to untreated diabetes or after excluding NHL cases that occurred within 3 years after the onset of diabetes. No interaction effect was found in the development of NHL between T2D and other potential risk factors. A linear inverse association was found between T2D duration and the risk of NHL in both men and women (Pfor linearity<0.01), with a highest risk of incident NHL in the first 5 years after the diagnosis of diabetes. Our study suggested that T2D might be associated with an increased risk of NHL.
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15
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Seliger C, Ricci C, Meier CR, Bodmer M, Jick SS, Bogdahn U, Hau P, Leitzmann MF. Diabetes, use of antidiabetic drugs, and the risk of glioma. Neuro Oncol 2015; 18:340-9. [PMID: 26093337 DOI: 10.1093/neuonc/nov100] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 05/07/2015] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Prior epidemiologic studies suggest inverse relations between diabetes and glioma risk, but the underlying mechanisms, including use of antidiabetic drugs, are unknown. METHODS We therefore performed a matched case-control analysis using the Clinical Practice Research Datalink (CPRD). We identified incident glioma cases diagnosed between 1995 and 2012 and matched each case with 10 controls on age, gender, calendar time, general practice, and years of active history in the CPRD. We performed conditional logistic regression to estimate odds ratios (ORs) with 95% CIs, adjusted for body mass index and smoking. RESULTS We identified 2005 cases and 20 050 controls. Diabetes was associated with decreased risk of glioma (OR = 0.74; 95% CI = 0.60-0.93), particularly glioblastoma (OR = 0.69; 95% CI = 0.51-0.94). Glioblastoma risk reduction was markedly pronounced among diabetic men (OR = 0.60; 95% CI = 0.40-0.90), most apparently for those with diabetes of long-term duration (OR for >5 vs 0 y = 0.46; 95% CI = 0.26-0.82) or poor glycemic control (OR for HbA1c ≥ 8 vs <6.5% = 0.20; 95% CI = 0.06-0.70). In contrast, the effect of diabetes on glioblastoma risk was absent among women (OR = 0.85; 95% CI = 0.53-1.36). No significant associations with glioma were found for use of metformin (OR for ≥ 30 vs 0 prescriptions = 0.72; 95% CI = 0.38-1.39), sulfonylureas (OR = 0.71; 95% CI = 0.39-1.30), or insulin (OR = 0.79; 95% CI = 0.37-1.69). CONCLUSIONS Antidiabetic treatment appears to be unrelated to glioma, but long-term diabetes duration and increased HbA1c both show decreased glioma risk. Stronger findings in men than women suggest low androgen levels concurrent with diabetes as a biologic mechanism.
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Affiliation(s)
- Corinna Seliger
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
| | - Cristian Ricci
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
| | - Christoph R Meier
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
| | - Michael Bodmer
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
| | - Susan S Jick
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
| | - Ulrich Bogdahn
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
| | - Peter Hau
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
| | - Michael F Leitzmann
- Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.)
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Araujo MM, Murashima AAB, Alves VM, Jamur MC, Hyppolito MA. The topical use of insulin accelerates the healing of traumatic Tympanic membrane perforations. Laryngoscope 2015; 126:156-62. [PMID: 25891948 DOI: 10.1002/lary.25300] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 02/09/2015] [Accepted: 03/09/2015] [Indexed: 12/29/2022]
Affiliation(s)
| | | | - Vani Maria Alves
- Department of Cell and Molecular Biology and Pathogenic Bioagents; Faculty of Medicine of Ribeirão Preto, University of São Paulo; Ribeirão Preto São Paulo Brazil
| | - Maria Célia Jamur
- Department of Cell and Molecular Biology and Pathogenic Bioagents; Faculty of Medicine of Ribeirão Preto, University of São Paulo; Ribeirão Preto São Paulo Brazil
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17
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Type 2 diabetes mellitus and risk of oral cancer and precancerous lesions: a meta-analysis of observational studies. Oral Oncol 2015; 51:332-40. [PMID: 25650271 DOI: 10.1016/j.oraloncology.2015.01.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 12/22/2014] [Accepted: 01/02/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Associations between type 2 diabetes mellitus (type 2 DM) and risk of oral cancer and precancerous lesions have been reported with controversial findings. We performed a meta-analysis to explore these associations. METHODS We identified studies by a literature search of MEDLINE and EMBASE through May 31, 2014, and by searching the reference lists of pertinent articles. Summary relative risk (SRR) with 95% confidence interval (CI) was calculated with a random-effects model. Between- study heterogeneity was assessed using the Cochran's Q and I(2) statistics. RESULTS A total of 13 studies (4 case-control and 9 cohort studies) on the association between type 2 DM and oral cancer were included. Overall analysis found that compared with non-diabetic individuals, individuals with type 2 DM had a significantly elevated incidence of oral cancer (SRR=1.15, 95% CI: 1.02-1.29; Pheterogeneity=0.277, I(2)=15.4%; 10 studies). Subgroup analyses found that duration of follow-up (⩾11years) significantly altered this positive association. Type 2 DM was associated with increased oral cancer mortality (SRR=1.41, 95% CI: 1.16-1.72; 4 studies). Meta-analysis of the four case-control studies showed a positive association between type 2 DM and risk of oral precancerous lesions (SRR=1.85, 95%CI: 1.23-2.80; Pheterogeneity=0.038, I(2)=57.5%). No significant public bias was found across these studies. CONCLUSIONS These findings of this meta-analysis indicate that compared with non-diabetic individuals, individuals with type 2 DM have an elevated risk of oral cancer and precancerous lesions development.
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18
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Paxton RJ, Jung SY, Vitolins MZ, Fenton J, Paskett E, Pollak M, Hays-Grudo J, Hursting SD, Chang S. Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers. Cancer Causes Control 2014; 25:1427-37. [PMID: 25238978 PMCID: PMC4316818 DOI: 10.1007/s10552-014-0434-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Accepted: 07/03/2014] [Indexed: 02/06/2023]
Abstract
PURPOSE Despite evidence that prolonged periods of sitting may influence biological mediators of cancer development, few studies have considered these relationships in a cancer-specific context. METHODS This cross-sectional study included 755 postmenopausal women enrolled in an ancillary study of the Women's Health Initiative. Plasma levels of Insulin-like growth factor-I (IGF-I), IGF-binding protein-3, leptin, insulin, C-peptide, C-reactive protein (CRP), and Interleukin (IL)-6 were measured. The time spent sitting per day was categorized as quartiles (Qs). The relationships between sedentary time and biomarkers were modified by race, physical activity, and exogenous estrogen use. RESULTS IGF-I levels among African American (AA) women were higher than those of white women across the Qs of sedentary time. Likewise, IL-6 levels in AA women were higher than those in white women at Q3 and Q4 of sedentary time. IGFBP-3 levels were higher and insulin levels were lower across the Qs of sedentary time among women meeting guidelines for physical activity than women who were not. Additionally, CRP levels were higher among estrogen users than nonusers at Q1, Q2, and Q4 of sedentary time. CONCLUSIONS These results suggest that relationship between time spent sitting and cancer-related biomarkers may not be simply linear, but differ in the context of effect modifiers.
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Affiliation(s)
- Raheem J. Paxton
- Department of Behavioral and Community Health, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Su Yon Jung
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Cancer Prevention Building, CPB7.3563, 1155 Pressler Street, Houston, TX 77030, USA
| | - Mara Z. Vitolins
- Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Jenifer Fenton
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA
| | - Electra Paskett
- Division of Cancer Prevention and Control, College of Medicine, Ohio State University, Columbus, OH, USA
| | - Michael Pollak
- Departments of Medicine and Oncology, McGill University, Montreal, QC, Canada
| | - Jennifer Hays-Grudo
- Department of Human Development and Family Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Stephen D. Hursting
- Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA
| | - Shine Chang
- Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Cancer Prevention Building, CPB7.3563, 1155 Pressler Street, Houston, TX 77030, USA
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19
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Szablewski L. Diabetes mellitus: influences on cancer risk. Diabetes Metab Res Rev 2014; 30:543-53. [PMID: 25044584 DOI: 10.1002/dmrr.2573] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2012] [Revised: 03/11/2013] [Accepted: 03/19/2013] [Indexed: 12/20/2022]
Abstract
Diabetes mellitus and cancer are common conditions, and their co-diagnosis in the same individual is not infrequent. The relative risks associated with type 2 diabetes are greater than twofold for hepatic, pancreatic, and endometrial cancers. The relative risk is somewhat lower, at 1.2-1.5-fold for colorectal, breast, and bladder cancers. In comparison, the relative risk of lung cancer is less than 1. The evidence for other malignancies (e.g. kidney, non-Hodgkin lymphoma) is inconclusive, whereas prostatic cancer occurs less frequently in male patients with diabetes. The potential biologic links between the two diseases are incompletely understood. Evidence from observational studies suggests that some medications used to treat hyperglycemia are associated with either increased or reduced risk of cancer. Whereas anti-diabetic drugs have a minor influence on cancer risk, drugs used to treat cancer may either cause diabetes or worsen pre-existing diabetes. If hyperinsulinemia acts as a critical link between the observed increased cancer risk and type 2 diabetes, one would predict that patients with type 1 diabetes would have a different cancer risk pattern than patients with type 2 diabetes because the former patients are exposed to lower levels of exogenous administered insulin. Obtained results showed that patients with type 1 diabetes had elevated risks of cancers of the stomach, cervix, and endometrium. Type 1 diabetes is associated with a modest excess cancer risk overall and risks of specific cancers that differ from those associated with type 2 diabetes.
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Affiliation(s)
- Leszek Szablewski
- Chair of General Biology and Parasitology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland
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20
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Starup-Linde J, Karlstad O, Eriksen SA, Vestergaard P, Bronsveld HK, de Vries F, Andersen M, Auvinen A, Haukka J, Hjellvik V, Bazelier MT, Boer AD, Furu K, De Bruin ML. CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis. Curr Drug Saf 2014; 8:296-332. [PMID: 24215312 PMCID: PMC5421136 DOI: 10.2174/15748863113086660071] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 10/27/2013] [Accepted: 10/30/2013] [Indexed: 12/11/2022]
Abstract
Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - Marie L De Bruin
- Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark.
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Al Haddad AHI, Adrian TE. Challenges and future directions in therapeutics for pancreatic ductal adenocarcinoma. Expert Opin Investig Drugs 2014; 23:1499-515. [PMID: 25078674 DOI: 10.1517/13543784.2014.933206] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. The 5-year survival of < 5% has not changed in decades. In contrast to other major cancers, the incidence of PDAC is increasing. AREAS COVERED The aims of this paper are first to analyze why PDAC is so difficult to treat and, second, to suggest future directions for PDAC therapeutics. The authors provide an article that is based on a comprehensive search through MEDLINE and the clinicalTrials.gov website. EXPERT OPINION Progress has been made recently. Notably, FOLFIRINOX or nab-paclitaxel plus gemcitabine provide survival benefit over gemcitabine alone, which was previously the mainstay of therapy for PDAC. Most of the current trials are testing combinations of repurposed drugs rather than addressing key targets in the PDAC pathogenesis. It is clear that to really make an impact on this disease, it will be necessary to address three different problems with targeted therapeutics. First, it is important to eradicate PDAC stem cells that result in recurrence. Second, it is important to reduce the peritumoral stroma that provides the tumors with growth support and provides a barrier to access of therapeutic agents. Finally, it is important to address the marked cachexia and metabolic derangement that contribute to morbidity and mortality and further complicate therapeutic intervention.
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Affiliation(s)
- Amal H I Al Haddad
- Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University , PO Box 17666, Al Ain , UAE
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22
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Noto H, Tsujimoto T, Noda M. Significantly increased risk of cancer in diabetes mellitus patients: A meta-analysis of epidemiological evidence in Asians and non-Asians. J Diabetes Investig 2014; 3:24-33. [PMID: 24843541 PMCID: PMC4014928 DOI: 10.1111/j.2040-1124.2011.00183.x] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Aims/Introduction: Emerging evidence from observational studies suggests that diabetes mellitus affects the cancer risk. However, whether there are differences in the magnitude of the influence of diabetes among ethnic groups is unknown. Materials and Methods: We searched MEDLINE and the Cochrane Library for pertinent articles that had been published as of 4 April 2011, and included them in a meta‐analysis of the risk of all‐cancer mortality and incidence in diabetic subjects. Results: A total of 33 studies were included in the meta‐analysis, and they provided 156,132 diabetic subjects for the mortality analysis and 993,884 for the incidence analysis. Cancer mortality was approximately 3%, and cancer incidence was approximately 8%. The pooled adjusted risk ratio (RR) of all‐cancer mortality was significantly higher than for non‐diabetic people (RR 1.32 [CI 1.20–1.45] for Asians; RR 1.16 [CI 1.01–1.34] for non‐Asians). Diabetes was also associated with an increased RR of incidence across all cancer types (RR 1.23 [CI 1.09–1.39] for Asians; RR 1.15 [CI 0.94–1.43] for non‐Asians). The RR of incident cancer for Asian men was significantly higher than for non‐Asian men (P = 0.021). Conclusions: Diabetes is associated with a higher risk for incident cancer in Asian men than in non‐Asian men. In light of the exploding global epidemic of diabetes, particularly in Asia, a modest increase in the cancer risk will translate into a substantial socioeconomic burden. Our current findings underscore the need for clinical attention and better‐designed studies of the complex interactions between diabetes and cancer. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00183.x, 2012)
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Affiliation(s)
- Hiroshi Noto
- Department of Diabetes and Metabolic Medicine, Center Hospital ; Department of Diabetes Research, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tetsuro Tsujimoto
- Department of Diabetes and Metabolic Medicine, Center Hospital ; Department of Diabetes Research, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Mitsuhiko Noda
- Department of Diabetes and Metabolic Medicine, Center Hospital ; Department of Diabetes Research, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
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Batabyal P, Vander Hoorn S, Christophi C, Nikfarjam M. Association of diabetes mellitus and pancreatic adenocarcinoma: a meta-analysis of 88 studies. Ann Surg Oncol 2014; 21:2453-62. [PMID: 24609291 DOI: 10.1245/s10434-014-3625-6] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced, incurable stage. Previous epidemiological data suggests that diabetes mellitus (DM) is a risk factor for PDAC, which may be important in early detection. However, the strength of this association needs to be determined, taking into account a number of recently published studies. METHODS A systematic review of the association between DM and PDAC was undertaken by searching electronic databases and journal references from 1973 to 2013. Summary estimates were obtained separately for case-control and cohort studies by means of a 'random effects' approach. Data pertaining to the DM was recorded and plotted at both an individual and study level, with the relative risks (RR) pooled separately to determine the relationship of DM duration and PDAC. RESULTS A total of 88 independent studies, including 50 cohort and 39 case-control studies were examined. The overall summary-combined RR was 1.97 (95 % CI 1.78-2.18) with marked heterogeneity that could not be clearly attributed to any subgroup analyses. The risk of PDAC was greatest early after the diagnosis of DM but remained elevated long after the diagnosis. The individual-level RR ranged from 6.69 at less than 1 year to 1.36 at 10 years. CONCLUSION The results demonstrate a strong association between PDAC and recently diagnosed DM, which may be attributed to a paraneoplastic effect. However, the presence of diabetes also remains a modest risk factor for the development of PDAC long-term. Selective screening of patients with new-onset DM for PDAC needs to be considered.
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Affiliation(s)
- Pikli Batabyal
- Department of Surgery, University of Melbourne, Austin Health, LTB 8, 145 Studley Rd, Heidelberg, Melbourne, VIC, 3084, Australia
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Pezzilli R, Pagano N. Is diabetes mellitus a risk factor for pancreatic cancer? World J Gastroenterol 2013; 19:4861-4866. [PMID: 23946590 PMCID: PMC3740415 DOI: 10.3748/wjg.v19.i30.4861] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2013] [Revised: 04/21/2013] [Accepted: 05/08/2013] [Indexed: 02/06/2023] Open
Abstract
The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long period of time. The importance of this topic is due to two main causes: the possible use of recent onset diabetes as a marker of the disease and, in particular, as a specific marker of pancreatic cancer, and the selection of a population at risk for pancreatic cancer. Thus, we decided to make an in-depth study of this topic; thus, we carried out an extensive literature search in order to re-assess the current knowledge on this topic. Even if diabetes is found a decade before the appearance of pancreatic cancer as reported in meta-analytic studies, we cannot select those patients already having non detectable pancreatic cancer, at least with the imaging and biological techniques available today. We believe that more studies are necessary in order to definitively identify diabetes mellitus as a risk factor for pancreatic cancer taking into consideration that approximately 10 years are needed to diagnose symptomatic pancreatic cancer. At present, the answer to the as to whether diabetes and pancreatic cancer comes first similar to the adage of the chicken and the egg is that diabetes is the egg.
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Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, Hirunpat S, Woodtichartpreecha P, Boonlikit S, Teerawattananon Y, Thakkinstian A. Risk factors of breast cancer: a systematic review and meta-analysis. Asia Pac J Public Health 2013; 25:368-87. [PMID: 23709491 DOI: 10.1177/1010539513488795] [Citation(s) in RCA: 113] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The etiology of breast cancer might be explained by 2 mechanisms, namely, differentiation and proliferation of breast epithelial cells mediated by hormonal factors. We performed a systematic review and meta-analysis to update effects of risk factors for both mechanisms. MEDLINE and EMBASE were searched up to January 2011. Studies that assessed association between oral contraceptives (OC), hormonal replacement therapy (HRT), diabetes mellitus (DM), or breastfeeding and breast cancer were eligible. Relative risks with their confidence intervals (CIs) were extracted. A random-effects method was applied for pooling the effect size. The pooled odds ratios of OC, HRT, and DM were 1.10 (95% CI = 1.03-1.18), 1.23 (95% CI = 1.21-1.25), and 1.14 (95% CI = 1.09-1.19), respectively, whereas the pooled odds ratio of ever-breastfeeding was 0.72 (95% CI = 0.58-0.89). Our study suggests that OC, HRT, and DM might increase risks, whereas breastfeeding might lower risks of breast cancer.
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26
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Rostoker R, Bitton-Worms K, Caspi A, Shen-Orr Z, LeRoith D. Investigating new therapeutic strategies targeting hyperinsulinemia's mitogenic effects in a female mouse breast cancer model. Endocrinology 2013; 154:1701-10. [PMID: 23515289 DOI: 10.1210/en.2012-2263] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Epidemiological and experimental studies have identified hyperinsulinemia as an important risk factor for breast cancer induction and for the poor prognosis in breast cancer patients with obesity and type 2 diabetes. Recently it was demonstrated that both the insulin receptor (IR) and the IGF-IR mediate hyperinsulinemia's mitogenic effect in several breast cancer models. Although IGF-IR has been intensively investigated, and anti-IGF-IR therapies are now in advanced clinical trials, the role of the IR in mediating hyperinsulinemia's mitogenic effect remains to be clarified. Here we aimed to explore the potential of IR inhibition compared to dual IR/IGF-IR blockade on breast tumor growth. To initiate breast tumors, we inoculated the mammary carcinoma Mvt-1 cell line into the inguinal mammary fat pad of the hyperinsulinemic MKR female mice, and to study the role of IR, we treated the mice bearing tumors with the recently reported high-affinity IR antagonist-S961, in addition to the well-documented IGF-IR inhibitor picropodophyllin (PPP). Although reducing IR activation, with resultant severe hyperglycemia and hyperinsulinemia, S961-treated mice had significantly larger tumors compared to the vehicle-treated group. This effect maybe secondary to the severe hyperinsulinemia mediated via the IGF-1 receptor. In contrast, PPP by partially inhibiting both IR and IGF-IR activity reduced tumor growth rate with only mild metabolic consequences. We conclude that targeting (even partially) both IR and IGF-IRs impairs hyperinsulinemia's effects in breast tumor development while simultaneously sparing the metabolic abnormalities observed when targeting IR alone with virtual complete inhibition.
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MESH Headings
- Animals
- Breast Neoplasms/complications
- Breast Neoplasms/genetics
- Breast Neoplasms/pathology
- Breast Neoplasms/therapy
- Carcinoma/complications
- Carcinoma/genetics
- Carcinoma/pathology
- Carcinoma/therapy
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Disease Models, Animal
- Female
- Growth Substances/adverse effects
- Hyperinsulinism/complications
- Hyperinsulinism/drug therapy
- Hyperinsulinism/genetics
- Hyperinsulinism/pathology
- Insulin/adverse effects
- Mammary Neoplasms, Experimental/complications
- Mammary Neoplasms, Experimental/genetics
- Mammary Neoplasms, Experimental/pathology
- Mammary Neoplasms, Experimental/therapy
- Mice
- Mice, Transgenic
- Molecular Targeted Therapy/methods
- Peptides/therapeutic use
- Podophyllotoxin/analogs & derivatives
- Podophyllotoxin/therapeutic use
- Receptor, IGF Type 1/antagonists & inhibitors
- Receptor, IGF Type 1/genetics
- Therapies, Investigational/methods
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Affiliation(s)
- Ran Rostoker
- Diabetes and Metabolism Clinical Research Center of Excellence, Clinical Research Institute at Rambam and the Faculty of Medicine, Technion, Haifa, Israel
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3D co-culturing model of primary pancreatic islets and hepatocytes in hybrid spheroid to overcome pancreatic cell shortage. Biomaterials 2013; 34:3784-94. [PMID: 23433671 DOI: 10.1016/j.biomaterials.2013.02.010] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Accepted: 02/02/2013] [Indexed: 12/29/2022]
Abstract
Here, a spheroidal 3D co-culture model of primary (rat) pancreatic islets and hepatocytes with uniform size and shape was developed using hemispheric concave microwell arrays. We conducted morphological and functional analyses of hybrid spheroids versus mono-cultures of islets or hepatocytes (controls). For the establishment of a 3D hybrid model, a broad range of cell ratios - 1:1, 1:3, 1:5, 1:7, 3:1, 5:1 and 7:1 mixture - of hepatocytes and pancreatic islets were used. As control, each hepatocyte and pancreatic islet were mono-cultured forming 3D spheroids. The transient morphology of spheroid formation in 9 culture models was observed using optical microscopy. Cell viability under these culture environments was assessed, and the morphologies of the outer and inner porous cell-spheroid structures were investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and imaging of stained spheroid sections. The pancreatic islet-specific function of hybrid spheroids was evaluated by measuring insulin secretion and in vivo test by xenotransplantation of encapsulated spheroids in microfibers with a consistent maintenance of normal blood glucose levels over 4 weeks, while liver-specific functions were measured in terms of albumin secretion, urea secretion and cytochrome P450 activity. These diverse observations and evaluations validated the positive and bidirectional effects of co-cultured 3D spheroids. The proposed 3D co-culture model demonstrated that both cells appeared to support each other's functions strongly in spheroids, even though smaller proportions of each cell type was evaluated compared to mono-culture models, suggesting that the proposed model could help overcome the problem of cell shortages in clinical applications.
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Yoon JM, Son KY, Eom CS, Durrance D, Park SM. Pre-existing diabetes mellitus increases the risk of gastric cancer: A meta-analysis. World J Gastroenterol 2013; 19:936-45. [PMID: 23429469 PMCID: PMC3574893 DOI: 10.3748/wjg.v19.i6.936] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2012] [Revised: 10/22/2012] [Accepted: 10/30/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To systematically assess the association between diabetes and incidence of gastric cancer.
METHODS: We searched MedLine (PubMed), EMBASE, and the Cochrane Library without any limitations with respect to publication date or language, we also searched the references of qualifying articles. Case-control studies and cohort studies comparing the risk of gastric cancer between diabetic patients and control subjects were included. We excluded studies reporting only standardized incidence ratios without control groups and those that investigated only mortality but not incidence. Seventeen studies met our criteria, and the qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. We performed a meta-analysis of pre-existing diabetes and gastric cancer incidence using the DerSimonian-Laird method for random-effects. For subgroup analyses, we separated the studies by study type, region, sex and method to determine confounding factors and reliability. We also conducted subgroup analyses to examine the effects of smoking, Helicobacter pylori (H. pylori) infection, and cancer site. Publication bias was evaluated using Begg’s test.
RESULTS: A random-effects model meta-analysis showed an increased gastric cancer risk in diabetic patients [relative risk (RR) = 1.19; 95%CI: 1.08-1.31]. Subgroup analyses indicated that this result persisted in cohort studies (RR = 1.20; 95%CI: 1.08-1.34), in studies on populations of both Western (RR = 1.18; 95%CI: 1.03-1.36) and Eastern countries (RR = 1.19; 95%CI: 1.02-1.38), in a female subgroup (RR=1.24; 95%CI: 1.01-1.52), and in highly qualified studies (RR = 1.17; 95%CI: 1.05-1.31). Moreover, these results persisted when the analysis was confined to studies adjusted for well-known gastric cancer risk factors such as smoking (RR = 1.17; 95%CI: 1.01-1.34) and H. pylori infection (RR = 2.35; 95%CI: 1.24-4.46).
CONCLUSION: Pre-existing diabetes mellitus may increase the risk of gastric cancer by approximately 19%. This effect seems to be unrelated to geographical region.
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Type 2 diabetes mellitus, oral diabetic medications, insulin therapy, and overall breast cancer risk. ISRN ENDOCRINOLOGY 2013; 2013:181240. [PMID: 23401790 PMCID: PMC3562674 DOI: 10.1155/2013/181240] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 01/01/2013] [Indexed: 12/19/2022]
Abstract
Breast cancer is among the most common cancers worldwide. Diabetes is an important chronic health problem associated with insulin resistance, increased insulin level, changes in growth hormones and factors, and activation of mitogen-activating protein kinase (MAPK) pathways, leading to an increased breast cancer risk. This paper looked at the epidemiologic studies of the association between type 2 diabetes and risk of breast cancer and its effect on overall cancer-specific survival. The combined evidence overall supported a modest association between type 2 diabetes and the risk of breast cancer, which was found to be more prevalent among postmenopausal women. Effect of oral diabetics and insulin therapy on breast cancer risk was also evaluated. It was found that metformin and thiazolidinones tended to have a protective role. Metformin therapy trials for its use as an adjuvant for breast cancer treatment are still ongoing. Sulfonylurea and insulin therapy were found to be mildly associated with increased overall cancers. No evidence or studies evaluated the association of DPPIV inhibitors and GLP 1 agonists with breast cancer risk because of their recent introduction into the management of diabetes.
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30
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Hardefeldt PJ, Edirimanne S, Eslick GD. Diabetes increases the risk of breast cancer: a meta-analysis. Endocr Relat Cancer 2012; 19:793-803. [PMID: 23035011 DOI: 10.1530/erc-12-0242] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13-1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07-1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79-1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99-1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.
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Affiliation(s)
- Prue J Hardefeldt
- Sydney Medical School Nepean, The Whiteley-Martin Research Centre, Discipline of Surgery, Nepean Hospital, The University of Sydney, Level 5, South Block, PO Box 63, Penrith, New South Wales 2751, Australia
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31
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Abstract
Background: The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research. Methods: A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk. Results: Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)). Conclusion: The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.
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32
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Johnson JA, Carstensen B, Witte D, Bowker SL, Lipscombe L, Renehan AG. Diabetes and cancer (1): evaluating the temporal relationship between type 2 diabetes and cancer incidence. Diabetologia 2012; 55:1607-18. [PMID: 22476947 DOI: 10.1007/s00125-012-2525-1] [Citation(s) in RCA: 162] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Accepted: 02/06/2012] [Indexed: 12/12/2022]
Abstract
Substantial evidence suggests that people with type 2 diabetes have an increased risk of developing several types of cancers. These associations may be due to a number of direct and indirect mechanisms. Observational studies of these associations, including the potential role for glucose-lowering therapy, are being increasingly reported, but face a number of methodological challenges. This paper is the first of two review papers addressing methodological aspects underpinning the interpretations of links between diabetes and cancer, and suggests potential approaches to study designs to be considered in observational studies. This paper reviews factors related to cancer incidence in the diabetic population; the second paper relates to studies of cancer mortality.
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Affiliation(s)
- J A Johnson
- School of Public Health, University of Alberta, 2040 Li Ka Shing Center, Edmonton, AB, Canada T6G 2E1.
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33
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Castillo JJ, Mull N, Reagan JL, Nemr S, Mitri J. Increased incidence of non-Hodgkin lymphoma, leukemia, and myeloma in patients with diabetes mellitus type 2: a meta-analysis of observational studies. Blood 2012; 119:4845-50. [PMID: 22496152 PMCID: PMC3367891 DOI: 10.1182/blood-2011-06-362830] [Citation(s) in RCA: 144] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Accepted: 03/28/2012] [Indexed: 12/21/2022] Open
Abstract
Hematologic malignancies are a heterogeneous group of conditions with an unclear etiology. We hypothesized that diabetes mellitus type 2 is associated with increased risk of developing lymphoma, leukemia, and myeloma. A literature search identified 26 studies (13 case-control and 13 cohort studies) evaluating such an association. Outcome was calculated as the odds ratio (OR) using a random effects model. Heterogeneity and publication bias were evaluated using the I(2) index and the trim-and-fill analysis, respectively. Quality was assessed using the Newcastle-Ottawa scale. The OR for non-Hodgkin lymphoma was increased at 1.22 (95% confidence interval [CI], 1.07-1.39; P < .01) but the OR for Hodgkin lymphoma was not. There was an increased OR for peripheral T-cell lymphoma (OR = 2.42, 95% CI, 1.24-4.72; P = .009) but not for other non-Hodgkin lymphoma subtypes. The OR for leukemia was 1.22 (95% CI, 1.03-1.44; P = .02) and the OR for myeloma was 1.22 (95% CI, 0.98-1.53; P = .08). Although diabetes mellitus type 2 seems to increase the risk of developing lymphoma, leukemia, and myeloma, future studies should focus on evaluating other potential confounders such as obesity, dietary habits, physical activity, and/or antidiabetic therapy.
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Affiliation(s)
- Jorge J Castillo
- Division of Hematology and Oncology, Rhode Island Hospital/The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02906, USA.
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Onitilo AA, Engel JM, Glurich I, Stankowski RV, Williams GM, Doi SA. Diabetes and cancer I: risk, survival, and implications for screening. Cancer Causes Control 2012; 23:967-81. [PMID: 22552844 DOI: 10.1007/s10552-012-9972-3] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2011] [Accepted: 04/14/2012] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes mellitus (DM) and cancer are common diseases that are frequently diagnosed in the same individual. An association between the two conditions has long been postulated. Here, we review the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. The risk for several cancers, including cancers of the pancreas, liver, colorectum, breast, urinary tract, and endometrium, is increased in patients with DM. In a pooled risk analysis weighting published meta-analytic relative risk (RR) for individual cancer by differences in their incidence rates, we found a population RR of 0.97 (95 % CI, 0.75-1.25) in men and 1.29 (95 % CI, 1.16-1.44) in women. All meta-analyses showed an increased relative risk for cancer in diabetic men, except studies of prostate cancer, in which a protective effect was observed. The relationship between diabetes and cancer appears to be complex, and at present, a clear temporal relationship between the two conditions cannot be defined. DM also impacts negatively on cancer-related survival outcomes and cancer screening rates. The overwhelming evidence for lower cancer screening rates, increased incidence of certain cancers, and poorer prognosis after cancer diagnosis in diabetic patients dictates a need for improved cancer care in diabetic individuals through improved screening measures, development of risk assessment tools, and consideration of cancer prevention strategies in diabetic patients. Part two of this review focuses on the biological and pharmacological mechanisms that may account for the association between DM and cancer.
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Affiliation(s)
- Adedayo A Onitilo
- Department of Hematology/Oncology, Marshfield Clinic Weston Center, 3501 Cranberry Boulevard, Weston, WI 54476, USA.
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35
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Janghorbani M, Dehghani M, Salehi-Marzijarani M. Systematic review and meta-analysis of insulin therapy and risk of cancer. Discov Oncol 2012; 3:137-46. [PMID: 22528451 DOI: 10.1007/s12672-012-0112-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2012] [Accepted: 04/09/2012] [Indexed: 12/13/2022] Open
Abstract
Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational studies was conducted to assess the risk of cancer during treatment with insulin. A search of online database through January 2011 was performed and examined the reference lists of pertinent articles, limited to observational studies in humans. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Fifteen studies (five case-control and ten cohort studies) were included, with 562,043 participants and 14,085 cases of cancer. Insulin treatment was associated with an increased risk of overall cancer [summary RR (95% CI)=1.39 (1.14, 1.70)]. Summary RR (9% CI) for case-control studies was 1.83 (0.99, 3.38), whereas RR for cohort studies was 1.28 (1.03, 1.59). These results were consistent between studies conducted in the USA and in Europe. For studies that included combined type 1 and 2 diabetes, the summary estimate was stronger than studies including only type 2 diabetes mellitus. The association between insulin treatment and cancer was stronger for pancreatic cancer [summary RR (95% CI)=4.78 (3.12, 7.32)] than for colorectal cancer [1.50 (1.08, 2.08)]. Insulin treatment was not associated with breast, prostate, and hepatocelluar cancer, and their effect estimates were not statistically significant. Our findings support an association between insulin use and increased risk of overall, pancreatic, and colorectal cancer.
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Affiliation(s)
- Mohsen Janghorbani
- Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran.
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Kutikhin AG, Yuzhalin AE. C-type lectin receptors and RIG-I-like receptors: new points on the oncogenomics map. Cancer Manag Res 2012; 4:39-53. [PMID: 22427730 PMCID: PMC3304337 DOI: 10.2147/cmar.s28983] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The group of pattern recognition receptors includes families of Toll-like receptors, NOD-like receptors, C-type lectin receptors, and RIG-I-like receptors. They are key sensors for a number of infectious agents, some of which are oncogenic, and they launch an immune response against them, normally promoting their eradication. Inherited variations in genes encoding these receptors and proteins and their signaling pathways may affect their function, possibly modulating cancer risk and features of cancer progression. There are numerous studies investigating the association of single nucleotide polymorphisms within or near genes encoding Toll-like receptors and NOD-like receptors, cancer risk, and features of cancer progression. However, there is an almost total absence of articles analyzing the correlation between polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors and cancer risk or progression. Nevertheless, there is some evidence supporting the hypothesis that inherited C-type lectin receptor and RIG-I-like receptor variants can be associated with increased cancer risk. Certain C-type lectin receptors and RIG-I-like receptors recognize pathogen-associated molecular patterns of potentially oncogenic infectious agents, and certain polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors may have functional consequences at the molecular level that can lead to association of such single nucleotide polymorphisms with risk or progression of some diseases that may modulate cancer risk, so these gene polymorphisms may affect cancer risk indirectly. Polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors thereby may be correlated with a risk of lung, oral, esophageal, gastric, colorectal, and liver cancer, as well as nasopharyngeal carcinoma, glioblastoma, multiple myeloma, and lymphoma. The list of the most promising polymorphisms for oncogenomic investigations may include rs1926736, rs2478577, rs2437257, rs691005, rs2287886, rs735239, rs4804803, rs16910526, rs36055726, rs11795404, and rs10813831.
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Affiliation(s)
- Anton G Kutikhin
- Department of Epidemiology, Kemerovo State Medical Academy, Kemerovo, Russian Federation
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37
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Wang P, Kang D, Cao W, Wang Y, Liu Z. Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta-analysis. Diabetes Metab Res Rev 2012; 28:109-22. [PMID: 21898753 DOI: 10.1002/dmrr.1291] [Citation(s) in RCA: 221] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Studies of diabetes and hepatocellular carcinoma (HCC) yielded inconsistent findings. This meta-analysis was conducted to examine the association between diabetes and risk of HCC. Studies were identified by searching PUBMED and MEDLINE database up to February 2011. Pooled risk estimates were calculated using the random-effects model. Potential sources of heterogeneity were explored by subgroup analyses. A total of 17 case-control studies and 32 cohort studies were included in the meta-analysis. The combined risk estimate of all studies showed a statistically significant increased risk of HCC prevalence among diabetic individuals (RR = 2.31, 95% CI: 1.87-2.84). The pooled risk estimate of 17 case-control studies (OR = 2.40, 95% CI: 1.85-3.11) was slightly higher than that from 25 cohort studies (RR = 2.23, 95% CI: 1.68-2.96). Metformin treatment was potentially protective. On the contrary, long duration of diabetes and sulfonylureas or insulin treatment possibly increase HCC risk. Also meta-analysis of 7 cohort studies found a statistically significant increased risk of HCC mortality (RR = 2.43, 95% CI: 1.66-3.55) for individuals with (versus without) diabetes. This meta-analysis shows that diabetes is associated with moderately increased risk of HCC prevalence, as well as HCC mortality. Considering the rapidly increasing prevalence of diabetes mellitus, the study underlines the need for cancer prevention in diabetic individuals. Further investigation is needed to focus on the potential mechanism for the pathogenesis of HCC and the link between HCC and different types, severity, treatment and duration of diabetes.
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Affiliation(s)
- Ping Wang
- School of Medicine, Shandong University, Jinan City, China
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38
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Noto H, Tsujimoto T, Sasazuki T, Noda M. Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr Pract 2012; 17:616-28. [PMID: 21454235 DOI: 10.4158/ep10357.ra] [Citation(s) in RCA: 109] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To conduct a review and meta-analysis of the effect of diabetes mellitus on the incidence of and mortality attributable to cancer at any anatomic site. METHODS We performed a search of MEDLINE and the Cochrane Library for pertinent articles published from the origin of these databases to July 5, 2010, and included them in a qualitative review and meta-analysis of the risk of all-cancer incidence and mortality in patients with diabetes. RESULTS Among patients with diabetes (n = 257,222) in 12 cohort studies, the cancer incidence was about 7%. The cancer mortality was approximately 3% among patients with diabetes (n = 152,091) in 19 cohort studies. The pooled adjusted risk ratio (RR) of all-cancer incidence was significantly elevated-RR, 1.10 (95% confidence interval [CI], 1.04 to 1.17) overall; RR, 1.14 (CI, 1.06 to 1.23) for men; and RR, 1.18 (CI, 1.08 to 1.28) for women. Diabetes was also associated with an increased RR of mortality across all cancer types-RR, 1.16 (CI, 1.03 to 1.30) overall; RR, 1.10 (CI, 0.98 to 1.23) for men; and RR, 1.24 (CI, 1.11 to 1.40) for women. CONCLUSION Cancer prevention and early detection by appropriate screening methods in patients with diabetes should be important components of clinical management and investigation, inasmuch as the exponentially increasing prevalence of diabetes will translate into substantial clinical and public health consequences on a global scale.
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Affiliation(s)
- Hiroshi Noto
- Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine, Tokyo, Japan
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Sella T, Chodick G, Barchana M, Heymann AD, Porath A, Kokia E, Shalev V. Gestational diabetes and risk of incident primary cancer: a large historical cohort study in Israel. Cancer Causes Control 2011; 22:1513-20. [PMID: 21847538 DOI: 10.1007/s10552-011-9825-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Accepted: 07/29/2011] [Indexed: 01/20/2023]
Abstract
PURPOSE Gestational diabetes mellitus (GDM), a state of glucose intolerance associated with pregnancy, is increasing in prevalence. Data regarding the cancer risk associated with GDM are sparse and limited to cancers of the breast and pancreas. This study was conducted to examine the risk of incident overall and site-specific malignancies associated with prior GDM in a historical cohort of women in a large health maintenance organization in Israel. METHODS All pregnant women aged 15-50 years who underwent 50-g glucose challenge tests between 13 March 1995 and 27 May 2009, without history of malignancy, diabetes, and infertility, were included. Clinical and demographic parameters at index date including age, socioeconomic level, BMI, and parity were collected. Diagnosis of gestational diabetes was based on the 100-g oral glucose tolerance test using Carpenter and Coustan criteria. Cancer diagnoses were obtained from the Israel Cancer Register through linkage data. RESULTS Among the 185,315 women who had undergone glucose challenge during the study period, 11,264 (6.1%) were diagnosed with GDM. During a total follow-up period of 1.05 million person-years (mean = 5.19 ± 3.9, median = 4.3), 2,034 incident cases of cancer were identified. GDM was associated with a hazard ratio (HR) of 7.06 (95% CI: 1.69-29.45) for pancreatic cancer (nine cases) and a HR of 1.70 (95% CI: 0.97-2.99) for hematological malignancies (177 cases). The association between GDM and hematological malignancies was limited to women with 5 or more years of follow-up (HR = 4.53; 95% CI: 1.81-11.31). CONCLUSION GDM is associated with an increased risk of pancreatic cancer and hematologic malignancies.
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Affiliation(s)
- Tal Sella
- Medical Division, Maccabi Healthcare Services, 27 Ha'Mered Street, Tel Aviv, Israel.
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Cancer risk in type 2 diabetes mellitus: metabolic links and therapeutic considerations. J Nutr Metab 2011; 2011:708183. [PMID: 21773024 PMCID: PMC3136221 DOI: 10.1155/2011/708183] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2010] [Revised: 02/10/2011] [Accepted: 03/24/2011] [Indexed: 12/14/2022] Open
Abstract
Type 2 diabetes mellitus (DM2) is increasing in incidence, creating worldwide public health concerns and impacting morbidity and mortality rates. An increasing number of studies have demonstrated shared associations between DM2 and malignancy, including key clinical, biochemical, and metabolic commonalities. This paper will attempt to explore the relationship between the various types of cancer and diabetes, the common metabolic pathways underlying cancer development, and the potential impact of various antidiabetes therapies on cancer risk.
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Schrauder MG, Fasching PA, Häberle L, Lux MP, Rauh C, Hein A, Bayer CM, Heusinger K, Hartmann A, Strehl JD, Wachter DL, Schulz-Wendtland R, Adamietz B, Beckmann MW, Loehberg CR. Diabetes and prognosis in a breast cancer cohort. J Cancer Res Clin Oncol 2011; 137:975-83. [PMID: 21132511 DOI: 10.1007/s00432-010-0960-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2010] [Accepted: 11/12/2010] [Indexed: 12/13/2022]
Abstract
PURPOSE Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics. METHODS The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes. RESULTS In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5 years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49-2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31-3.97). CONCLUSION In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5 years follow-up period.
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Affiliation(s)
- Michael G Schrauder
- Department of Obstetrics and Gynaecology, University Hospital Erlangen, Erlangen, Germany.
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Lipscombe L. Insulin, Insulin Resistance, and Cancer Associations. ENERGY BALANCE AND CANCER 2011. [DOI: 10.1007/978-1-4419-9911-5_5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions. Blood 2010; 116:e90-8. [PMID: 20699439 DOI: 10.1182/blood-2010-06-289561] [Citation(s) in RCA: 189] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and "in situ" lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications.
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Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AKL, Gans ROB, de Vries EGE. Metformin: taking away the candy for cancer? Eur J Cancer 2010; 46:2369-80. [PMID: 20656475 DOI: 10.1016/j.ejca.2010.06.012] [Citation(s) in RCA: 300] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2010] [Accepted: 06/07/2010] [Indexed: 12/16/2022]
Abstract
Metformin is widely used in the treatment of diabetes mellitus type 2 where it reduces insulin resistance and diabetes-related morbidity and mortality. Population-based studies show that metformin treatment is associated with a dose-dependent reduction in cancer risk. The metformin treatment also increases complete pathological tumour response rates following neoadjuvant chemotherapy for breast cancer, suggesting a potential role as an anti-cancer drug. Diabetes mellitus type 2 is associated with insulin resistance, elevated insulin levels and an increased risk of cancer and cancer-related mortality. This increased risk may be explained by activation of the insulin- and insulin-like growth factor (IGF) signalling pathways and increased signalling through the oestrogen receptor. Reversal of these processes through reduction of insulin resistance by the oral anti-diabetic drug metformin is an attractive anti-cancer strategy. Metformin is an activator of AMP-activated protein kinase (AMPK) which inhibits protein synthesis and gluconeogenesis during cellular stress. The main downstream effect of AMPK activation is the inhibition of mammalian target of rapamycin (mTOR), a downstream effector of growth factor signalling. mTOR is frequently activated in malignant cells and is associated with resistance to anticancer drugs. Furthermore, metformin can induce cell cycle arrest and apoptosis and can reduce growth factor signalling. This review discusses the role of diabetes mellitus type 2 and insulin resistance in carcinogenesis, the preclinical rationale and potential mechanisms of metformin's anti-cancer effect and the current and future clinical developments of metformin as a novel anti-cancer drug.
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Affiliation(s)
- Mathilde Jalving
- Department of Medical Oncology, University Medical Centre Groningen, Groningen, The Netherlands.
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Krechler T, Jáchymová M, Mestek O, Žák A, Zima T, Kalousová M. Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of RAGE and glyoxalase I genes in patients with pancreas cancer. Clin Biochem 2010; 43:882-6. [DOI: 10.1016/j.clinbiochem.2010.04.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2009] [Revised: 03/10/2010] [Accepted: 04/01/2010] [Indexed: 01/16/2023]
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Shu X, Ji J, Li X, Sundquist J, Sundquist K, Hemminki K. Cancer risk among patients hospitalized for Type 1 diabetes mellitus: a population-based cohort study in Sweden. Diabet Med 2010; 27:791-7. [PMID: 20636960 DOI: 10.1111/j.1464-5491.2010.03011.x] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIMS Type 1 diabetes mellitus (T1DM) is an autoimmune disease with potential mechanistic links to immune-related cancers. We aimed at examining the overall and specific cancer risks among hospitalized T1DM patients from the national registers in Sweden. METHODS A T1DM research cohort was created by identifying T1DM patients from the Hospital Discharge Register and linking them with the Cancer Registry. Standardized incidence ratios (SIRs) for subsequent cancers were calculated among patients with T1DM compared with those without T1DM. RESULTS Two hundred and fifty-eight cases were ascertained with subsequent cancers during the follow-up duration from 1964 to 2006, with an increased overall SIR of 1.17 (95% CI 1.04-1.33) among 24 052 T1DM patients identified at baseline. Significant excess was noted for gastric and skin (squamous cell carcinoma) cancers and for leukaemia. Increased risk of acute lymphatic leukaemia accounted for most of the variation of leukaemia risk (SIR = 5.31, 95% CI 3.32-8.05). Cancer risk varied with sex, age at first hospitalization and numbers of hospitalizations. The risk was higher in women compared with men and in those hospitalized for T1DM at age over 10 years compared with the younger patients. Higher risks were also found among those with more hospital visits. CONCLUSION By quantifying the variations of overall and site-specific cancer risks after T1DM, the current study provides novel associations between T1DM and subsequent cancers, the mechanisms of which remain to be established.
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Affiliation(s)
- X Shu
- Center for Family and Community Medicine, Karolinska Institute, Alfred Nobels allé 12, Huddinge, Sweden.
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Tung HD, Wang JH, Tseng PL, Hung CH, Kee KM, Chen CH, Chang KC, Lee CM, Changchien CS, Chen YD, Lu SN. Neither diabetes mellitus nor overweight is a risk factor for hepatocellular carcinoma in a dual HBV and HCV endemic area: community cross-sectional and case-control studies. Am J Gastroenterol 2010; 105:624-31. [PMID: 20051944 DOI: 10.1038/ajg.2009.711] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are well-known risk factors for hepatocellular carcinoma, and diabetes mellitus (DM) and overweight have also been reported as risk factors for hepatocellular carcinoma (HCC). We tried to elucidate the roles of DM and overweight in HCC development in a dual HBV and HCV endemic area of southern Taiwan. METHODS In 2004, a community-based comprehensive screening program was conducted in Tainan County. Hepatitis B surface antigen (HBsAg), anti-HCV, alpha-fetoprotein, complete blood counts, triglyceride, cholesterol, and glucose levels were examined. DM was defined as fasting blood sugar >126 mg per 100 ml, and overweight was defined as a body mass index >24 kg m(-2). Subjects with thrombocytopenia (platelet count <150 x 10(9) l(-1)) and elevated alpha-fetoprotein (>20 ng ml(-1)) underwent ultrasonographic screening for HCC. A total of 56,307 adults (>40 years old) participated, and 72 new HCC cases were detected and confirmed. RESULTS In comparisons of all 72 HCC cases with the other 144 individual age-, sex-, residency-, HBsAg-, and anti-HCV-matched controls, only thrombocytopenia and high alanine transaminase (ALT) levels were shown to be independent risk factors. Neither DM nor overweight was shown to be significant in any of the analyses. CONCLUSIONS On the basis of the community-based cross-sectional and case-controlled studies, neither DM nor overweight was a risk factor for HCC in a dual HBV and HCV endemic area. However, male gender, age (> or =65 years), HBsAg, anti-HCV, thrombocytopenia, and high ALT levels were independent risk factors for HCC.
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Affiliation(s)
- Hung-Da Tung
- Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Abstract
Hepatocellular carcinoma (HCC) is a common form of cancer that arises from hepatocytes and whose risk may be affected by several known environmental factors, including hepatitis viruses, alcohol, cigarette smoking, and others. Rare monogenic syndromes, such as alpha1-antitrypsin deficiency, glycogen storage disease type I, hemochromatosis, acute intermittent and cutanea tarda porphyria, as well as hereditary tyrosinemia type I are associated with a high risk of HCC. Several common conditions or diseases inherited as polygenic traits e.g. autoimmune hepatitis, type 2 diabetes, a family history of HCC, hypothyroidism, and non-alcoholic steatohepatitis also show an increased risk of HCC compared to the general population. Overall, the genetic susceptibility to HCC is characterized by a genetic heterogeneity; a high individual risk of HCC may thus be caused by several unlinked single gene defects, whose carriers are rare in the general population, or by more common conditions inherited by complex genetics.
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Affiliation(s)
- Tommaso A Dragani
- Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, Milan, Italy.
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Hong SG, Jung SJ, Joo MK, Lee BJ, Yeon JE, Park JJ, Byun KS, Bak YT. [Prevalence of pancreatic cancer in diabetics and clinical characteristics of diabetes-associated with pancreatic cancer--comparison between diabetes with and without pancreatic cancer]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2009; 54:167-73. [PMID: 19844153 DOI: 10.4166/kjg.2009.54.3.167] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND/AIMS In Korea, the prevalence of pancreatic cancer (PC) in general population has been reported as 7 in 100,000. However, that in diabetes mellitus (DM) has not been elucidated yet. This study was designed to estimate the prevalence of PC among DM patients, and characterize and compare the patients with DM with and without PC. METHODS 5,082 patients (4,890 DM without PC, 78 PC with DM, and 114 PC without DM) were enrolled from Korea University Guro Hospital during a period of 4 years between January 2004 and January 2008. RESULTS The prevalence of PC in DM patients was 1.6% and that of DM in PC patients was 40.6%. No significant differences in the clinical characteristics except HbAIc and ALP were observed between PC patients with DM and without DM. Among 78 PC patients with DM, DM was diagnosed in 19 (29.4%) and 29 (37.1%) patients concomitantly or within 2 years prior to the diagnosis of PC, respectively. Among the cases with recent onset DM (less than 2 years duration), the disease duration of DM before the diagnosis of PC was less than 1 year in 14 patients (17.9%) and 1 to 2 years in 15 patients (19.2%). DM patients with PC were found to have significantly higher ALT, total bilirubin, and ALP levels than in DM patients without PC. CONCLUSIONS The prevalence of PC in DM patients was 1.6% and was higher than in the general population. Recent onset DM was frequent in PC patients (less than 2 years duration). We recommend close follow-up for at least 2 years in new-onset diabetes.
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Affiliation(s)
- Seung Goun Hong
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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