One-Carbon Metabolism and Methylation in Breast Tumors
Abstract
This work comprised a molecular epidemiology study of breast cancer where two minority PHD students were funded to conduct studies that directly led to their successful PHD defenses (Sumner and Llanos). The study considered genetic susceptibilities and biomarkers for breast cancer risk, using a breast cancer case control study and a cross-sectional study of health women undergoing reduction mammoplasty. The hypotheses centered around the role of diet, specifically folate intake and its relationship to carcinogenesis--hypermethylation, p53 mutational mechanisms and estrogen receptor status. For the MTHFR C677T and A1298C mutations, while there were no statistically significant results, the results went in opposite directions for pre-and postmenopausal women, indicating the heterogeneity of these tumors and that the susceptibility has differing effects in the context of one's menopausal status and carcinogenic pathways associated with that. For diet, there were associations for higher levels of folate with having a breast tumor that was positive for p16 in premenopausal and postmenopausal women, consistent with our hypothesis that folate has a direct effect in breast carcinogenesis through one carbon metabolism and hypermethylation. There was a clear association for increased folate, B6 and B12 intake intake and having an ER+ tumor compared to an ER- tumor in premenopausal women. Noted was a dose response effect. Given that ER silencing happens through hypermethylation, and etiological relationship to folate and nutrient exposure is supported with this work. Also noted is that plasma folate is associated with BMI and plasma leptin, indicating other pathways besides one carbon metabolism for the role of folate in breast cancer risk.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2007
- Accession Number
- ADA586990
Entities
People
- Adana Llanos
- Simone Sumner
Organizations
- Georgetown University