One - Carbon Metabolism and Methylation in Breast Tumors
Abstract
The first aim of this case control study is to examine the risk of breast cancer in relation to germ-line variants found in three key enzymes related to one-carbon metabolism. We also planned to determine the methylation status of several genes in our cases and to identify any association with polymorphisms found in enzymes related to one-carbon metabolism. Finally we determined the ER status of all cases in an attempt to identify associations with p53 mutations. In the last year I have completed the analyses for p16 and the statistical analyses with p53. This year, I successfully defended my PhD thesis. I have not submitted any papers because of the increased work preparing the defense. New this year, there were some interesting findings for genetic susceptibilities and p16 hypermethylation, as well as some dietary associations. 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 the MTHFR A1298C mutation, there was a borderline association for the AG+GG genotypes in premenopausal women comparing P16+ cases to p16- cases. 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. For B6, there was a borderline association for higher levels of exposure and p16 positive tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA587001
Entities
People
- Simone Sumner
Organizations
- Georgetown University