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

Abstract

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.

One-Carbon Metabolism Nutrients and Epigenetics: A Mechanistic Link Between Aberrant One-Carbon Metabolism and Cancer Risk?

“…One study which was restricted to women with type I endometrial cancer demonstrated a null association (Liu et al 2013 ). Another large prospective study demonstrated a similar lack of effect of both dietary and total folate intakes on both type I and type II endometrial cancer (Uccella et al 2011b ). Interestingly, however, this study reported a signifi cantly increased risk of type II endometrial cancer associated with supplemental intakes of folic acid (Uccella et al 2011b ).…”

“…The joint effect of vitamin B 6 and the MTHFR 677TT genotype demonstrates the intricate gene-nutrient interactions between one-carbon nutrients and genes involved in the one-carbon transfer reaction pathway. Two prospective studies revealed that vitamin B 6 intakes from diet and supplements were not associated with type I endometrial cancer risk (Liu et al 2013 ) and supplemental intakes, similar to folic acid, was associated with an increased risk of type II endometrial cancer only (Uccella et al 2011b ).…”

“…Similarly, two prospective studies revealed that vitamin B 12 intakes from diet and supplements were not associated with type I endometrial cancer risk (Liu et al 2013 ) whereas the second study demonstrated that supplemental intake, similar to folic acid, has been found to be associated with an increased risk only in type II endometrial cancer (Uccella et al 2011b ).…”

“…Type II endometrial cancer is characterized by a high frequency of p53 mutations and chromosomal instability (Uccella et al 2011b ). Therefore, investigation of global DNA hypomethylation, a contributor to DNA instability, and gene-specifi c DNA methylation of the p53 gene as well as other genes which have been found to be hypermethylated in endometrial cancer may further elucidate the mechanistic underpinnings of endometrial cancer.…”

Role of Laparoscopy in the Treatment of Endometrial Cancer in Women Over 70 Years of Age

“…Заболеваемость и биоло-гическая активность РЭ увеличиваются в течение жиз-ни [4,5], что связано с увеличением числа факторов риска.…”