Risk Factors for Pancreatic Cancer among Nonsmokers and Nondrinkers of Alcohol in the Women’s Health Initiative

Abstract Background: Pancreatic cancer is a highly aggressive malignancy primarily affecting older adults. Risk factors include smoking and alcohol consumption. To investigate potential contributors to pancreatic cancer risk among individuals without these exposures, we examined pancreatic cancer risk in postmenopausal women in the Women’s Health Initiative who were never-smokers and nondrinkers. Methods: The study included 40,205 women (ages 50–79 years at enrollment) who were never-smokers/nondrinkers at enrollment. Information on reproductive health and lifestyle factors was obtained at baseline. Diabetes was reported at baseline and during follow-up. Pancreatic cancer cases were centrally adjudicated. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox regression. Results: Over an average follow-up of 16.6 years, 336 incident cases of pancreatic cancer were ascertained. High body mass index (HR ≥35 vs. ≥18.5 to <20 kg/m2, 1.42; 95% CI, 1.02–2.01), large height-adjusted waist circumference (HR ≥88 vs. < 80 cm, 1.51; 95% CI, 1.16–1.97), and diabetes (HR, 1.53; 95% CI, 1.18–1.98) were associated with increased risk. Higher quality diet (HRalternative healthy eating index 2010–SD unit, 0.89; 95% CI, 0.80–0.99), and higher consumption of fruit and vegetables (HR ≥7 vs. ≤1.5 serving/day, 0.57; 95% CI, 0.33–0. 99) and fiber (HR ≥20 vs. <10 g/day, 0.60; 95% CI, 0.39–0.92) were associated with reduced risk, whereas higher intake of red meat was associated with an increased risk (HR ≥0.5 vs. <0.5 serving/day, 1.28; 95% CI, 1.00–1.64). No associations were observed for physical activity or reproductive/hormonal factors. Conclusions: Among never-smoking/nondrinking postmenopausal women, excessive adiposity, diabetes, and several dietary factors were associated with altered pancreatic cancer risk. Impact: These findings, which are consistent with those in the general population, are the first to highlight potential risk factors for pancreatic cancer among low-risk women.