Abstract 2160: Metformin use is not associated with pancreatic cancer risk in a clinic-based case-control study conducted in the San Francisco Bay Area, California

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Patients with pancreatic cancer (PC) are commonly diagnosed at advanced stages of the disease, at which point cure is no longer possible. A better understanding of risk or protective factors for PC may inform prevention and/or early detection strategies. Metformin, a commonly used drug for type II diabetes (DM2), has been shown in some observational clinical studies to reduce the risk of several cancer types, including PC. Its antineoplastic effects occur through inhibition of mammalian target of rapamycin (mTOR) and induction of cell cycle arrest and apoptosis, among other mechanisms. The current case-control study addresses two distinct research questions: whether metformin use is associated with PC risk among those with DM2, and whether metformin modulates the risk of PC associated with DM2. We recruited 536 cases and 869 controls, predominantly from University of California, San Francisco (UCSF) medical and surgical oncology clinics (cases) and general medicine clinics (controls), over a six-year period (2006-2011). Controls were frequency-matched to cases by sex and age in 5-year groups. Case diagnoses were confirmed by patient medical record and cancer registry data. Direct interviews were conducted by trained interviewers using an epidemiological risk factor questionnaire. The association between metformin use and PC risk among diabetics was analyzed using propensity score-weighted unconditional logistic regression, whereas the effect of metformin use on the association between DM2 and PC in the total study population was analyzed using standard multivariable logistic models. Metformin was the most common anti-diabetic drug used by DM2 study participants (66.5%). Among DM2 participants (N=170), ever use of metformin was not associated with PC risk in adjusted models (OR: 1.01, 95%CI: 0.61-1.68). Similarly, duration of metformin use was not statistically significantly associated with PC risk when also adjusted for DM2 duration. Among the total study population (N=1405), DM2 was not statistically significantly associated with PC risk (adjusted OR: 1.28, 95%CI: 0.81-2.00). However, risk was inversely associated with DM2 duration; participants whose DM2 was diagnosed 1-5 years prior to PC diagnosis/interview were at markedly increased risk (OR: 2.47, 95%CI: 1.25-4.85). Stratification of participants with DM2 by metformin use revealed no difference in risk between never (OR: 1.44, 95%CI: 0.78-2.67) and ever users (OR: 1.19, 95%CI: 0.72-1.99) relative to non-DM2 participants. PC risk also did not differ across groups of metformin or DM2 duration. In this clinic-based case-control study of PC, metformin use was not associated with PC risk. Specifically, our results suggest that metformin is neither associated with PC risk in those with DM2, nor does it attenuate or exacerbate PC risk associated with DM2. Citation Format: Evan J. Walker, Andrew H. Ko, Elizabeth A. Holly, Paige M. Bracci. Metformin use is not associated with pancreatic cancer risk in a clinic-based case-control study conducted in the San Francisco Bay Area, California. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2160. doi:10.1158/1538-7445.AM2014-2160