DNA Repair Gene Polymorphisms in Hereditary and Sporadic Breast Cancer
Abstract
Genetic breast cancer risk factors for sporadic and familial breast cancer may be elucidated through studies of women with BRCA1 mutations or in women in high risk breast/ovarian cancer families. There is variable penetrance for breast cancer among women in families with known BRCA1 mutations, and we hypothesize that this might be due to genetic variants in wild-type BRCA1 or other DNA repair genes and we hypothesized that these genetic variants might also affect sporadic breast cancer risk. The purpose of this study is to identify genotype-phenotype relationships in DNA repair-related genes using EBV-immortalized cell strains in women by assessing radiation-induced DNA repair capacity. Seventy-five affected and 57 unaffected BRCA1 mutation carriers with immortalized cell lines were analyzed in this study. Radiation-induced chromosomal breaks were measured as a marker of DNA repair capacity and the method was validated by assessing intra-individual variation in EBV-immortalized and peripheral blood lymphocytes. Concordant samples were analyzed and the Pearson correlation was found to be high (r2=0.865, p=0.01). There was inter-individual variation in mean breaks per cell among the 132 women. Affected women were 3 times more likely to have higher mean breaks per cell than unaffected women. When unconditional logistic regression was done, no association between BRCA1 mutations, polymorphisms, haplotypes, or BRCA2 polymorphisms and DNA repair efficiency was found. Subjects with high mean breaks per cell were 2-fold more likely to be diagnosed with infiltrating ductal carcinoma and 4 times more likely to be diagnosed with metastatic breast cancer compared to subjects with low mean breaks per cell. The variable penetrance for breast cancer risk among BRCA1 carriers has not been explained by common polymorphisms in BRCA1 or BRCA2, or haplotypes of BRCA1 in this model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2006
- Accession Number
- ADA452743
Entities
People
- Luisel Ricks-santi
Organizations
- Georgetown University