Dietary intake of isoflavones and coumestrol and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Background: Although phytoestrogens modulated pancreatic tumour growth in experimental studies, it remains unclear whether phytoestrogen intake is associated with pancreatic cancer. Methods: Of 92,278 persons who completed the Diet History Questionnaire in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 346 were diagnosed with pancreatic cancer within a median follow-up of 9.4 years. Cox proportional hazards regression was used to evaluate pancreatic cancer risk in relation to phytoestrogen intake. Results: After adjustment for confounders, intakes of glycitein and formononetin were associated with a reduced risk of pancreatic cancer [highest vs. lowest quartile, hazard ratio (HR) (95% confidence interval (CI)) for glycitein: 0.60 (0.39, 0.92); P for linear trend: 0.01; HR for formononetin: 0.51 (0.37, 0.70); P for linear trend: 0.005]. These associations were stronger and their linear trends across the quartiles of intakes were more statistically significant among ever smokers than never-smokers. A reduced risk was also observed for ever smokers in the highest quartile of total isoflavones or daidzein compared with those in the lowest quartile. Conclusions: Our study suggests that high intakes of total isoflavones and some individual isoflavones were inversely associated with pancreatic cancer risk, but this potential protective effect was confined to ever smokers.