Friday, November 4, 2011

One-carbon metabolism and breast cancer epigenetics!

something tells me the one-carbon epi field is about to heat up.... read all about it in this month's Epigenetics --

The influence of one-carbon metabolism on gene promoter methylation in a population-based breast cancer study.

Xu X, Gammon MD, Jefferson E, Zhang Y, Cho YH, Wetmur JG, Teitelbaum SL, Bradshaw PT, Terry MB, Garbowski G, Hibshoosh H, Neugut AI, Santella RM, Chen J.



Abnormal methylation in gene promoters is a hallmark phenomenon of the cancer genome including breast cancer; however, factors that may influence promoter methylation have not been well elucidated. One-carbon metabolism provides the universal methyl donor for methylation reactions; perturbation of one-carbon metabolism might influence DNA methylation and ultimately, affect gene functions. Utilizing ~800 breast cancer tumor tissues from a large population-based study, we investigated the relationships of dietary and genetic factors involved in the one-carbon metabolism pathway with promoter methylation of a panel of 13 breast cancer related genes. We found CCND2, HIN1 and CHD1 are the more "dietary sensitive" as their promoter methylation was associated with intakes of at least two out of eight dietary methyl factors examined. On the other hand, some micronutrients (i.e. B 2 and B 6) are more "epigenetically active" as their intake levels were correlated with promoter methylation status of 3 out of 13 breast cancer genes. Both positive (hypermethylation) and inverse (hypomethylation) associations with high micronutrient intakes were observed. Unlike the dietary factors, we did not observe any clear patterns between one-carbon genetic polymorphism and 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 potentially reversible, dietary intervention may offer promising venues for cancer intervention and prevention.

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