title: The influence of one-carbon metabolism on gene promoter methylation in a population-based breast cancer study.
abstract: Abnormal methylation in gene promoters is a hallmark of the cancer genome; however, factors that may influence promoter methylation have not been well elucidated. As the one-carbon metabolism pathway provides the universal methyl donor for methylation reactions, perturbation of this pathway might influence DNA methylation and, ultimately, affect gene functions. Utilizing approximately 800 breast cancer tumor tissues from a large population-based study, we investigated the relationships between dietary and genetic factors involved in the one-carbon metabolism pathway and promoter methylation of a panel of 13 breast cancer-related genes. We found that CCND2, HIN1 and CHD1 were the most "dietary sensitive" genes, as methylation of their promoters was associated with intakes of at least two out of the eight dietary methyl factors examined. On the other hand, some micronutrients (i.e., B 2 and B 6) were more "epigenetically active" as their intake levels correlated with promoter methylation status in 3 out of the 13 breast cancer genes evaluated. Both positive (hypermethylation) and inverse (hypomethylation) associations with high micronutrient intake were observed. Unlike what we saw for dietary factors, we did not observe any clear patterns between one-carbon genetic polymorphisms and the promoter methylation status of the genes examined. Our results provide preliminary evidence that one-carbon metabolism may have the capacity to influence the breast cancer epigenome. Given that epigenetic alterations are thought to occur early in cancer development and are potentially reversible, dietary modifications may offer promising venues for cancer intervention and prevention.
authors: Research Center for Translational Medicine, Shanghai East Hospital of Tongji University School of Medicine, Shanghai, China. xu_xinran@hotmail.com
authors: Xinran
authors: X
authors: Xu
authors: Marilie D
authors: MD
authors: Gammon
authors: Elizabeth
authors: E
authors: Jefferson
authors: Yujing
authors: Y
authors: Zhang
authors: Yoon Hee
authors: YH
authors: Cho
authors: James G
authors: JG
authors: Wetmur
authors: Susan L
authors: SL
authors: Teitelbaum
authors: Patrick T
authors: PT
authors: Bradshaw
authors: Mary Beth
authors: MB
authors: Terry
authors: Gail
authors: G
authors: Garbowski
authors: Hanina
authors: H
authors: Hibshoosh
authors: Alfred I
authors: AI
authors: Neugut
authors: Regina M
authors: RM
authors: Santella
authors: Jia
authors: J
authors: Chen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002244:Carbon / Q000378:metabolism*; D056742:Cyclin D2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D004032:Diet; D057890:Epigenomics; D005260:Female; D006801:Humans; D018977:Micronutrients / Q000378:metabolism; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D016207:Cytokines; D004268:DNA-Binding Proteins; D018977:Micronutrients; C434732:SCGB3A1 protein, human; D025521:Tumor Suppressor Proteins; D002244:Carbon; D004265:DNA Helicases; C080359:CHD1 protein, human