Dietary Folate Intake,MTHFRGenetic Polymorphisms, and the Risk of Endometrial Cancer among Chinese Women

Abstract

Folate plays an important role in carcinogenesis. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), encoded by the MTHFR gene, is involved in this process. We investigated both the independent and joint effects of dietary folate and other methyl-related nutrients, as well as three polymorphisms of MTHFR (677C>T, 1298A>C, and 1793G>A), on endometrial cancer risk in a population-based case-control study. Between 1997 and 2003, 1,204 newly diagnosed endometrial cancer cases and 1,212 controls were recruited among women between the ages of 30 and 69 years in urban Shanghai, China. Information on dietary intake of folate and other methyl-related nutrients, including vitamin B2 (riboflavin), vitamin B6, vitamin B12, and methionine, was derived from a validated food frequency questionnaire. Genotyping was completed on 1,041 cases and 1,030 controls for MTHFR 677C>T (rs1801133), 1298A>C (rs1801131), and 1793 G>A (rs22749746). Haplotype estimation of the three single-nucleotide polymorphisms was performed using PHASE software. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate associations of nutrients, MTHFR genotypes, and haplotypes with endometrial cancer risk. A significant inverse association between dietary folate intake and endometrial cancer risk was observed among all subjects and non -B vitamin supplement users. The greatest reduction in endometrial cancer risk was observed among non-users of supplements in the highest quartile of dietary folate intake (OR, 0.5; 95% CI, 0.4-0.7) as compared with those in the lowest quartile. Dietary intake of folate cofactors (methionine, vitamin B2, vitamin B6, and vitamin B12) was not related to risk of endometrial cancer. No association was observed between endometrial cancer and the MTHFR 677C>T, 1298 A>C, and 1793G>A polymorphisms or derived haplotypes. Among non-users of supplements, however, the 1298C and 1793A alleles were associated with a lower risk of endometrial cancer among women with high dietary folate intake but related to a higher risk among those with low dietary folate intake (P interaction = 0.08 and 0.03, respectively). Further analysis showed that the lowest risk (OR, 0.6; 95% CI, 0.4-1.1) was among women with the 1298C allele and the highest intake of both folate and riboflavin (P interaction = 0.04). A similar association was observed for the 1793A allele (P interaction = 0.03). Our findings suggest that folate intake may decrease the risk of endometrial cancer and modify the effect of MTHFR polymorphisms on risk. (Cancer Epidemiol Biomarkers Prev 2007;16(2):281 -7)

Dietary intake of selected B vitamins in relation to risk of major cancers in women

“…A second case -control study (Ferraroni et al, 1994) reported a significant inverse association of thiamin intake with colon cancer risk in both males and females, but found no association with niacin or folate intake. In a large case -control study from China (Xu et al, 2007), intake of riboflavin was not associated with endometrial cancer risk. To our knowledge, no cohort studies have reported on the association of thiamin, riboflavin, or niacin with any of the cancers addressed here.…”

“…Findings regarding the association of methionine with cancers of the breast, endometrium, and ovary have generally been null (Thorand et al, 1998;Shrubsole et al, 2001;Feigelson et al, 2003;Tworoger et al, 2006;Xu et al, 2007;Cho et al, 2007a), whereas for colorectal cancer, the findings have been mixed, with some suggesting an inverse association (Giovannucci et al, 1993(Giovannucci et al, , 1995(Giovannucci et al, , 1998 and others showing no association (Ferraroni et al, 1994;Slattery et al, 1997;Flood et al, 2002;Harnack et al, 2002). We are unaware of any previous studies that have examined the association of methionine intake and lung cancer risk.…”

“…Furthermore, few studies have assessed the roles of thiamin, riboflavin, or niacin in relation to the risk of commonly occurring cancers (Jedrychowski et al, 2002;van den Donk et al, 2005;Xu et al, 2007).…”

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

“…Negri et al [12] suggested an inverse association between folate intake and the risk of this malignancy, which was replicated in a casecontrol study by Xu et al [13]. Conversely, others have reported no association between folate intake and endometrial cancer risk [14,15].…”

Folate intake, Methylenetetrahydrofolate Reductase Polymorphisms in Association with the Prognosis of Esophageal Squamous Cell Carcinoma

“…The role of folate intake and MTHFR C677T polymorphism on survival of patients has also been reported in different types of malignancies, including endometrial cancer, breast cancer, rectal cancer and esopheageal cancer (Shrubsole et al, 2001;Jiang et al, 2005;Xu et al, 2007). However, the results is inconsistent (Miller et al, 1988;Shen et al, 2001;Jain et al, 2008;Upadhyay et al, 2008).…”