Sex Disparities and Female Reproductive and Hormonal Factors Associated with Risk of Pancreatic Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Abstract

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15-1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC among women with greater attained body height, meat consumption and cigarettes smoked (1.12 (1.05-1.19) per 5 cm, 1.18 (1.02-1.36) per 100 g/d, 1.42 (1.27-1.59) per 10/d; respectively). Among child-bearing women, long cumulative duration of breastfeeding was inversely associated with risk of PC (HR 0.74, 95% CI 0.61-0.89) for >5.7 months of breastfeeding (median) relative to <= 5.7 months and among HRT users, cumulative duration of HRT use was inversely associated with PC risk (HR 0.71, 95% CI 0.53-0.95, >2.4 versus <= 2.4 years). Further reproductive and hormonal factors, such as age at menarche, number of full-term pregnancies, age at menopause, or use of oral contraceptives, were not significantly associated with PC risk. Conclusions: Pooled analyses of large cohort studies are needed to confirm these results, and detailed data on the type and intensity of HRT are required to better evaluate its effect.