A Cohort Study of Metformin and Colorectal Cancer Risk among Patients with Diabetes Mellitus

被引:55
作者
Bradley, Marie C. [1 ]
Ferrara, Assiamira [2 ]
Achacoso, Ninah [2 ]
Ehrlich, Samantha F. [2 ]
Quesenberry, Charles P., Jr. [2 ]
Habel, Laurel A. [2 ]
机构
[1] NCI, Div Canc Control & Populat Sci, Epidemiol & Genom Res Program, Rockville, MD USA
[2] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA
关键词
CLINICAL-TRIALS; REDUCED RISK; THERAPY; METAANALYSIS; POPULATION; INSULIN; MALIGNANCIES; MORTALITY; OUTCOMES; BIASES;
D O I
10.1158/1055-9965.EPI-17-0424
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these biases. Methods: A cohort study was conducted among 47,351 members of Kaiser Permanente Northern California with diabetes and no history of cancer or metformin use. Follow-up for incident colorectal cancer occurred from January 1, 1997, until June 30, 2012. Cox regression was used to calculate HRs and 95% confidence intervals (C-Is) for colorectal cancer risk associated with metformin use (ever use, total duration, recency of use, and cumulative dose). Results: No association was observed between ever use of metforrnin and colorectal cancer risk (HR, 0.90; 95% Cl, 0.76-1.07) and there was no consistent pattern of decreasing risk with increas-ing total duration, dose, or recency of use. However, long-term use (>5.0 years) appeared to be associated with reduced risk of colorectal cancer in the full population (HR, 0.78; 95% CI, 0.60-1.02), among current users (HR. 0.78; 95% CI, 0.59-1.04), and in men (HR, 0.65; 95% Cl, 0.45-0.94) but not in women. Higher cumulative doses of metformin were associated with reduced risk. In initial users of sulfonylureas, switching to or adding metformin was also associated with decreased colorectal cancer risk Condusions: Our findings showed an inverse association between long-term use of metformin and colorectal cancer risk. Findings, especially the risk reduction among men, need to be confirmed in large, well-conducted studies. Impact: If our findings are confirmed, metformin may have a role in the chemoprevention of colorectal cancer. Cancer Epidentiol Biortiarkers Prey; 27(5); 525-30. (C) 2018 AACR. See related cornmentaiy by Jackson and Garcia-Albenj; p. 520
引用
收藏
页码:525 / 530
页数:6
相关论文
共 36 条
[1]   Metformin and neoplasia: Implications and indications [J].
Aljada, Ahmad ;
Mousa, Shaker A. .
PHARMACOLOGY & THERAPEUTICS, 2012, 133 (01) :108-115
[2]  
[Anonymous], 2014, SEER CANC STAT REV 1
[3]   Use of Metformin Is Not Associated with a Decreased Risk of Colorectal Cancer: A Case-Control Analysis [J].
Bodmer, Michael ;
Becker, Claudia ;
Meier, Christian ;
Jick, Susan S. ;
Meier, Christoph R. .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2012, 21 (02) :280-286
[4]   Long-term use of metformin and colorectal cancer risk in type II diabetics: a population-based case-control study [J].
Cardel, Majken ;
Jensen, Sara M. ;
Pottegard, Anton ;
Jorgensen, Trine L. ;
Hallas, Jesper .
CANCER MEDICINE, 2014, 3 (05) :1458-1465
[5]   The influence of glucose-lowering therapies on cancer risk in type 2 diabetes [J].
Currie, C. J. ;
Poole, C. D. ;
Gale, E. A. M. .
DIABETOLOGIA, 2009, 52 (09) :1766-1777
[6]   Understanding the benefit of metformin use in cancer treatment [J].
Dowling, Ryan J. O. ;
Goodwin, Pamela J. ;
Stambolic, Vuk .
BMC MEDICINE, 2011, 9
[7]   Cohort Study of Pioglitazone and Cancer Incidence in Patients With Diabetes [J].
Ferrara, Assiamira ;
Lewis, James D. ;
Quesenberry, Charles P., Jr. ;
Peng, Tiffany ;
Strom, Brian L. ;
Van den Eeden, Stephen K. ;
Ehrlich, Samantha F. ;
Habel, Laurel A. .
DIABETES CARE, 2011, 34 (04) :923-929
[8]   Metformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review [J].
Franciosi, Monica ;
Lucisano, Giuseppe ;
Lapice, Emanuela ;
Strippoli, Giovanni F. M. ;
Pellegrini, Fabio ;
Nicolucci, Antonio .
PLOS ONE, 2013, 8 (08)
[9]   Metformin Increases Overall Survival in Patients with Diabetes Undergoing Surgery for Colorectal Cancer [J].
Fransgaard, Tina ;
Thygesen, Lau Caspar ;
Gogenur, Ismail .
ANNALS OF SURGICAL ONCOLOGY, 2016, 23 (05) :1569-1575
[10]   Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and Confounders [J].
Gandini, Sara ;
Puntoni, Matteo ;
Heckman-Stoddard, Brandy M. ;
Dunn, Barbara K. ;
Ford, Leslie ;
DeCensi, Andrea ;
Szabo, Eva .
CANCER PREVENTION RESEARCH, 2014, 7 (09) :867-885