Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: A prospective cohort study

Background: Type I and II endometrial cancer are biologically and clinically distinct, with type II cancers having a high frequency of p53 mutations and an association with chromosomal instability. This raises the hypothesis that onecarbon nutrients (folate, methionine, and the enzymic cofactors vitamins B2, B6, and B12), which mediate chromosomal stability and DNA methylation, may be protective for type II but not type I endometrial cancer. Methods: Using a prospective cohort of 23 356 postmenopausal women followed 20 years, we estimated the relative risks (RRs) of type I (N = 471) and II (N = 71) endometrial cancers according to intake of one-carbon nutrients, adjusting for confounders. Results: No associations were observed between dietary or supplemental intake of any one-carbon nutrient and risk of type I cancer. For type II cancer, positive associations were due to supplemental, rather than dietary, intake of these nutrients: supplemental folate (RR = 1.80 for >228.6 versus 0 lg/day; P trend = 0.027) and vitamins B2 (RR = 1.94 for >1.70 versus 0 mg/day; P trend = 0.011), B6 (RR = 2.08 for >2.00 versus 0 mg/day; P trend = 0.012), and B12 (RR = 2.10 for >3.43 versus 0 lg/day; P trend = 0.0060). Conclusion: Contrary to our hypothesis, use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.