One-carbon metabolism factors and endometrial cancer risk

Background: This is the largest prospective cohort analysis to assess how dietary factors involved in one-carbon metabolism are associated with endometrial cancer incidence, using 26 years of follow-up data from the Nurses' Health Study. Methods: The prospective cohort analysis of one-carbon metabolism dietary factors used the Cox proportional hazards model, and incorporated 788 incident endometrial cancer events from 1980 to 2006. Genotyping and unconditional logistic regression were performed on 572 endometrial cancer cases and their matched controls to examine 29 mostly non-synonymous single-nucleotide polymorphisms involved in one-carbon metabolism. Results: There were no significant dose-response relationships between intake of any of the one-carbon metabolism dietary factors and endometrial cancer incidence, but alcohol consumption of <1 drink a day was significantly protective (hazard ratio: 0.80; 95% CI: 0.68, 0.94). Those with the MTHFR 677 TT or MTHFR 1298 CC genotype had more protective associations for many of the dietary factors and endometrial cancer, but statistical power was limited in this analysis. Conclusion: Dietary levels of folate, choline, methionine, vitamin B2, vitamin B6 or vitamin B12 do not appear to influence endometrial cancer incidence. Moderate alcohol intake may protect against developing endometrial cancer.