This Article Full Text Full Text (PDF) Correction (v17,p743) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, W.-H. Articles by Shu, X. O. Search for Related Content PubMed PubMed Citation Articles by Xu, W.-H. Articles by Shu, X. O.

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

¹ Department of Epidemiology, Shanghai Cancer Institute; ² Department of Epidemiology, Fu Dan University School of Public Health, Shanghai, P.R. China; and ³ Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University, and Vanderbilt-Ingram Cancer Center, Medical Center East, Nashville, Tennessee

Requests for reprints: Xiao Ou Shu, Vanderbilt Epidemiology Center, 6009 Medical Center East, Vanderbilt University, 1215 21st Avenue South, Nashville, TN 37232-8300. Phone: 615-936-0713; Fax: 615-936-1269. E-mail: Xiao-Ou.Shu{at}vanderbilt.edu

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)

This article has been cited by other articles:

				Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 743 - 743. [Full Text] [PDF]