Abstract A105: Intakes of folate, methionine, and vitamin B6 and B12 and risk of esophageal and gastric cancer in a large cohort study

Background: Folate and other nutrients in the one-carbon metabolism pathway play essential roles in DNA synthesis and methylation, and may be critically involved in carcinogenesis. Low folate intake has been linked to the development of breast, colorectal and pancreatic cancer, and the effect may be modulated by other factors such as alcohol drinking and smoking. Up to date, few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer. Method: We examined the association between the intakes of folate, methionine, and vitamin B6 and B12 and gastric and esophageal cancer in the National Institutes of Health–AARP Diet and Health Study (492,293 men and women, aged 50 to 71 at baseline in 1995-1996). Dietary and supplemental intakes of such nutrients were assessed with a food frequency questionnaire at baseline. Total intake is a sum of dietary and supplemental intakes. Cancer cases were ascertained by linkage to state cancer registries. A multivariate Cox proportional hazard model was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: During an average of 9 years of follow up, we identified 815 and 935 incident cases of esophageal and gastric cancer, respectively. The median intake of dietary folate in the lowest (Q1), the middle (Q3) and the highest quintile (Q5) were 275, 405, and 595 mcg/d, respectively. Compared to Q3, Q1 of dietary folate intake was associated with a significantly higher risk of esophageal cancer (RR =1.33, 95% CI, 1.08, 1.64), while no further risk reduction was observed in Q5 (RR =1.01, 95% CI, 0.79, 1.28). The elevated risk in Q1 in relation to Q3 was more pronounced in esophageal squamous cell carcinoma (RR =1.91, 95% CI, 1.17, 3.10) than in esophageal adenocarcinoma (RR =1.22, 95% CI, 0.96, 1.54), and was observed across subgroups of alcohol consumption and smoking (RR (95% CI): 1.49 (0.95, 2.33) in nondrinkers, 1.25 (0.91, 1.72) in drinkers of >0-15 g/d of alcohol consumption, and 1.33 (0.92, 1.91) in drinkers of >15 g/d; and 1.29 (0.76, 2.18) in never smokers and 1.29 (1.02, 1.63) in ever smokers). Among other nutrients, low dietary intake of vitamin B6 was also associated with increased risk of esophageal cancer (Q1 vs. Q3: RR =1.30, 95% CI, 1.05, 1.61), and gastric cancer (Q1 vs. Q3: RR =1.22, 95% CI, 0.99, 1.50). There was a similar L-shaped association between esophageal cancer and total intake of folate and vitamin B6. No association was observed with methionine or vitamin B12. Conclusion: Our findings suggest that low intake of folate and vitamin B6 was associated with increased risk of esophageal cancer while higher intake of these nutrients did not provide additional benefits. Citation Format: Qian Xiao, Jiansong Ren, Christian Abnet, Yikyung Park. Intakes of folate, methionine, and vitamin B6 and B12 and risk of esophageal and gastric cancer in a large cohort study. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A105.