Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study

Jonathan L Wright, Janet L Stanford, Jonathan L Wright, Janet L Stanford

Abstract

Purpose: Metformin is a commonly used medication for type II diabetes mellitus. Epidemiologic studies have suggested a decreased relative risk of cancer with metformin use, and preclinical studies of prostate cancer (PCa) have shown antitumor activity with metformin. In this study, we explore the relationship between metformin use and PCa risk in a population-based case-control study.

Methods: Cases were men aged 35-74 years diagnosed with PCa between 2002 and 2005 in King County, Washington. Controls were frequency matched by age and identified by random digit dialing. Use of metformin was determined from in-person questionnaires regarding medical and prescription history. The relationship of metformin use with PCa risk was evaluated using logistic regression.

Results: A total of 1,001 cases of PCa and 942 controls were available for analysis. In Caucasian men, metformin use was more common in controls than in cases (4.7 vs. 2.8%, p = 0.04), resulting in a 44% risk reduction for PCa (adjusted OR = 0.56; 95% CI 0.32-1.00). No association was seen in African-American men.

Conclusion: Metformin use was associated with a borderline significant decrease in the relative risk of PCa in Caucasians. Further study into this relationship is needed to confirm the association and determine the underlying pathways involved.

References

    1. Ries L, Melbert D, Krapcho M, Stinchcomb D, Howlader N, Horner M et al. (2008) SEER cancer statistics review, 1975–2005, based on November 2007 SEER data submission, posted to the SEER web site. Cited; available from:
    1. Kasper JS, Liu Y, Giovannucci E. Diabetes mellitus and risk of prostate cancer in the health professionals follow-up study. Int J Cancer. 2009;124(6):1398–1403. doi: 10.1002/ijc.24044.
    1. Waters KM, Henderson BE, Stram DO, Wan P, Kolonel LN, Haiman CA. Association of diabetes with prostate cancer risk in the multiethnic cohort. Am J Epidemiol. 2009;169(8):937–945. doi: 10.1093/aje/kwp003.
    1. Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006;29(2):254–258. doi: 10.2337/diacare.29.02.06.dc05-1558.
    1. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330(7503):1304–1305. doi: 10.1136/bmj.38415.708634.F7.
    1. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009;8(1):88–96.
    1. Zhuang Y, Miskimins WK. Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal. 2008;3:18. doi: 10.1186/1750-2187-3-18.
    1. Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, et al. Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res. 2007;67(14):6745–6752. doi: 10.1158/0008-5472.CAN-06-4447.
    1. Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, et al. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 2008;27(25):3576–3586. doi: 10.1038/sj.onc.1211024.
    1. Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 2007;67(22):10804–10812. doi: 10.1158/0008-5472.CAN-07-2310.
    1. Schneider MB, Matsuzaki H, Haorah J, Ulrich A, Standop J, Ding XZ, et al. Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology. 2001;120(5):1263–1270. doi: 10.1053/gast.2001.23258.
    1. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 2006;66(21):10269102–10269173. doi: 10.1158/0008-5472.CAN-06-1500.
    1. Zakikhani M, Dowling RJ, Sonenberg N, Pollak MN. The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. Cancer Prev Res (Phila Pa) 2008;1(5):369–375.
    1. Algire C, Zakikhani M, Blouin MJ, Shuai JH, Pollak M. Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth. Endocr Relat Cancer. 2008;15(3):833–839. doi: 10.1677/ERC-08-0038.
    1. Agalliu I, Salinas CA, Hansten PD, Ostrander EA, Stanford JL. Statin use and risk of prostate cancer: results from a population-based epidemiologic study. Am J Epidemiol. 2008;168(3):250–260. doi: 10.1093/aje/kwn141.
    1. Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574–579. doi: 10.1056/NEJM199602293340906.
    1. Top 200 Generic Drugs by Units in 2006. Drug Topics
    1. Murtola TJ, Tammela TL, Lahtela J, Auvinen A. Antidiabetic medication and prostate cancer risk: a population-based case-control study. Am J Epidemiol. 2008;168(8):925–931. doi: 10.1093/aje/kwn190.
    1. Peek ME, Cargill A, Huang ES. Diabetes health disparities: a systematic review of health care interventions. Med Care Res Rev. 2007;64(5 Suppl):101S–156S. doi: 10.1177/1077558707305409.
    1. Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009;27(20):3297–3302. doi: 10.1200/JCO.2009.19.6410.
    1. Hede K. Doctors seek to prevent breast cancer recurrence by lowering insulin levels. J Natl Cancer Inst. 2008;100(8):530–532. doi: 10.1093/jnci/djn119.
    1. Hammarsten J, Hogstedt B. Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur J Cancer. 2005;41(18):2887–2895. doi: 10.1016/j.ejca.2005.09.003.
    1. Ma J, Li H, Giovannucci E, Mucci L, Qiu W, Nguyen PL, et al. Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis. Lancet Oncol. 2008;9(11):1039–1047. doi: 10.1016/S1470-2045(08)70235-3.
    1. Hardie DG. Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology. 2003;144(12):5179–5183. doi: 10.1210/en.2003-0982.
    1. Hadad SM, Fleming S, Thompson AM. Targeting AMPK: a new therapeutic opportunity in breast cancer. Crit Rev Oncol Hematol. 2008;67(1):1–7. doi: 10.1016/j.critrevonc.2008.01.007.
    1. Centers for Disease Control and Prevention (CDC) State-specific incidence of diabetes among adults–participating states, 1995–1997 and 2005–2007. MMWR Morb Mortal Wkly Rep. 2008;57(43):1169–1173.
    1. Werny DM, Saraiya M, Gregg EW. Prostate-specific antigen values in diabetic and nondiabetic US men, 2001–2002. Am J Epidemiol. 2006;164(10):978–983. doi: 10.1093/aje/kwj311.

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