%0 Journal Article
%T Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk
%A Luisel J Ricks-Santi
%A Lara E Sucheston
%A Yang Yang
%A Jo L Freudenheim
%A Claudine J Isaacs
%A Marc D Schwartz
%A Ramona G Dumitrescu
%A Catalin Marian
%A Jing Nie
%A Dominica Vito
%A Stephen B Edge
%A Peter G Shields
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-278
%X 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).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.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.The genetic determinants of breast cancer are under intensive study. Some women with a strong family history of breast cancer inherit BRCA1 or BRCA2 mutations, which have a variable penetrance for breast cancer, between 40 to 66% [1], suggesting that additional factors contribute to cancer risk among BRCA1 and BRCA2 carriers. For sporadic cancers, however, many low-penetrant single-nucleotide polymorphisms (SNPs) have been investigated in pathways ranging from growth factor signaling to DNA repair. Yet, it has been difficult to find consistency across study results [2-4], due to differences in study populations, sample sizes and study designs [5]. However, studies of high risk populations generally help uncover the molecular mechanisms of a disease and provide guidance and direction for studies of sporadic disease. While BRCA1 and BRCA2 mutations are highly penetrant [1], resulting in higher risk for breast cancer,
%U http://www.biomedcentral.com/1471-2407/11/278