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- Title
Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk.
- Authors
Ricks-Santi, Luisel J.; Sucheston, Lara E.; Yang Yang; Freudenheim, Jo L.; Isaacs, Claudine J.; Schwartz, Marc D.; Dumitrescu, Ramona G.; Marian, Catalin; Jing Nie; Vito, Dominica; Edge, Stephen B.; Shields, Peter G.
- Abstract
Background: Inter-individual variation in DNA repair capacity is thought to modulate breast cancer risk. The phenotypic mutagen sensitivity assay (MSA) measures DNA strand breaks in lymphocytes; women with familial and sporadic breast cancers have a higher mean number of breaks per cell (MBPC) then women without breast cancer. Here, we explore the relationships between the MSA and the Rad51 gene, which encodes a DNA repair enzyme that interacts with BRCA1 and BRCA2, in BRCA1 mutation carriers and women with sporadic breast cancer. Methods: Peripheral blood lymphoblasts from women with known BRCA1 mutations underwent the MSA (n = 138 among 20 families). BRCA1 and Rad51 genotyping and sequencing were performed to identify SNPs and haplotypes associated with the MSA. Positive associations from the study in high-risk families were subsequently examined in a population-based case-control study of breast cancer (n = 1170 cases and 2115 controls). Results: Breast cancer diagnosis was significantly associated with the MSA among women from BRCA1 families (OR = 3.2 95%CI: 1.5-6.7; p = 0.004). The Rad51 5'UTR 135 C>G genotype (OR = 3.64; 95% CI: 1.38, 9.54; p = 0.02), one BRCA1 haplotype (p = 0.03) and in a polygenic model, the E1038G and Q356R BRCA1 SNPs were significantly associated with MBPC (p = 0.009 and 0.002, respectively). The Rad51 5'UTR 135C genotype was not associated with breast cancer risk in the population-based study. Conclusions: Mutagen sensitivity might be a useful biomarker of penetrance among women with BRCA1 mutations because the MSA phenotype is partially explained by genetic variants in BRCA1 and Rad51.
- Subjects
GENETIC polymorphisms; DNA repair; GENETIC mutation; BREAST cancer; LYMPHOCYTES
- Publication
BMC Cancer, 2011, Vol 11, Issue 1, p278
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/1471-2407-11-278