Background. Dietary nutrients involved in one-carbon metabolism, either as methyl donors or as enzyme co-factors are hypothesized to protect against pancreatic cancer development. Animal studies showed that diets deficient in one carbon metabolism-related nutrients, such as vitamin B6 and choline, were able to induce DNA damage in the pancreas and enhance the development of carcinogen-initiated pancreatic cancers in rodents. Although there is a strong rationale that one carbon metabolism-related nutrients may alter pancreatic cancer risk in human, prospective studies with well-characterized dietary intake that test the hypothesis are lacking. Methods. Between 1993 and 1998, 63,257 men and women aged 45-74 years were recruited into the Singapore Chinese Health Study. By the end of 2013, 271 incident pancreatic cancer cases were identified during up to 20 years of follow-up, after excluding individuals with extreme calorie intake or a history of cancer at enrollment (N = 2,959). The daily intakes of betaine, choline, folate, methionine, and vitamins B2, B6 & B12 were assessed at baseline by a 165-item semi-quantitative food frequency questionnaire that was developed for, and validated in the study population. Hazard ratios (HRs) and 95% confidence intervals (CIs) for pancreatic cancer risk associated with total calorie-adjusted intake levels of one carbon nutrients were calculated using the Cox-proportional hazard regression method with the adjustment for established risk factors for pancreatic cancer including age, sex, body mass index (BMI), smoking, alcohol drinking, and diabetes. Results. Higher intake of vitamin B6 and choline were associated with a statistically significant decrease in the risk of developing pancreatic cancer. Compared with the lowest quartile, HRs (95% CIs) for the 2nd, 3rd, and 4th quartiles of vitamin B6 were 0.71 (0.51-0.98), 0.80 (0.58-1.11), and 0.52 (0.36-0.74), respectively (P trend = 0.001). Similarly, the corresponding HRs (95% CIs) for choline were 0.57 (0.40-0.80), 0.72 (0.52-1.00), and 0.67 (0.48-0.93), respectively (P trend = 0.04). There was no overall statistically significant relationship between dietary intake of betaine, folate, methionine, vitamins B2 or B12 and pancreatic cancer risk. In stratified analyses by sex, the statistically significant, inverse associations between dietary choline and vitamin B6 and pancreatic cancer risk were present among men only (both P trend ≤0.02). Among men, these inverse associations were more apparent in smokers and nondrinkers of alcoholic beverages. Conclusion. Our prospective findings are consistent with in vivo evidence for protective roles of vitamin B6 and choline on pancreatic cancer development. These dietary compounds may be developed as potential chemopreventive agents against pancreatic cancer development in humans.

Citation Format: Joyce Y. Huang, Lesley M. Butler, Renwei Wang, Ai Zhen Jin, Woon-Puay Koh, Jian-Min Yuan. Dietary intake of vitamin B6 and choline are inversely associated with pancreatic cancer risk: The Singapore Chinese Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1882. doi:10.1158/1538-7445.AM2015-1882