Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk
By Luisel J Ricks-Santi, Lara Sucheston, Yang Yang, J. Freudenheim, Claudine Isaacs, Marc D. Schwartz, R. Dumitrescu, C. Marian, J. Nie, D. Vito and 2 more. 2011
22 citations recorded by the source corpus.
BackgroundInter-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.MethodsPeripheral 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).ResultsBreast 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.ConclusionsMutagen 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.
Subfields: Genetics, Molecular Biology, Pathology and Forensic Medicine
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Citations in the corpus
- EgoNet: identification of human disease ego-network modules (2014, background): “One recent study suggested the association of RAD51 polymorphis with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk [43].”