|Mason, Joel b.|
|Mccann, Susan e.|
|Platek, Mary e.|
|Edge, Stephen b.|
|Krishan, Shiva s.|
|Shields, Peter g.|
|Freudenheim, Jo l.|
Submitted to: Nutrition and Cancer
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/11/2011
Publication Date: 10/4/2011
Citation: Tao, M., Mason, J., Marian, C., Mccann, S., Platek, M., Millen, A., Ambrosone, C., Edge, S., Krishan, S., Trevisan, M., Shields, P., Freudenheim, J. 2011. Promoter methylation of E-cadherin, p16, and RAR-beta(2) genes in breast tumors and dietary intake of nutrients important in one-carbon metabolism. Nutrition and Cancer. 63(7):1143-1150. Interpretive Summary: There is evidence that habitual intake of the B-vitamin, folate, and other related B vitamins in part determine a woman’s risk of developing breast cancer. One way it might do this is by altering so-called ‘gene methylation’: of important cancer-related genes, which are slight modifications in the chemical structure of the genes. This study examined several hundred breast cancers. The methylation modifications of 3 important genes were defined for each tumor. These alterations in gene methylation were then compared to each individual’s history of the intake of vitamins B2, B6, B12 and folate. There was no discernible relationship between the intake of these B-vitamins and methylation of these genes in human breast cancer. However, many other potent forces alter gene methylation in cancers so this study does not exclude the possibility that intake of these vitamins might alter gene methylation in normal breast tissue and thereby influence the emergence of breast cancers at an earlier stage of development than we examined.
Technical Abstract: Aberrant DNA methylation plays a critical role in carcinogenesis, and the availability of dietary factors involved in 1-carbon metabolism may contribute to aberrant DNA methylation. We investigated the association of intake of folate, vitamins B(2), B(6), B(12), and methionine with promoter methylation of E-cadherin, p16, and RAR-beta(2) genes in archived tumor tissues from incident, primary breast cancer cases in a population-based case-control study. Real-time methylation-specific PCR was performed on 803 paraffin-embedded samples; usual dietary intake was queried from a food frequency questionnaire. Unconditional logistic regression was used to derive adjusted odds ratios and 95% confidence intervals for likelihood of promoter methylation for high compared to low intake of those 1-carbon nutrients. Overall, in case-case comparisons, dietary intakes of folate, vitamins B(2), B(6), B(12), and methionine were not associated with likelihood of promoter methylation of E- cadherin, p16, and RAR-ß(2) for all cases combined or within strata defined by menopausal status and estrogen receptor status in this study. This finding, however, does not exclude the possibility that intake of such nutrients might have the ability to modulate promoter methylation in normal or premalignant (dysplastic) breast tissue.