association of rad51 polymorphism with dna repair in brca1 mutation carriers and sporadic breast cancer risk协会rad51多态性的dna修复brca1突变携带者和零星的乳腺癌风险.pdfVIP

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association of rad51 polymorphism with dna repair in brca1 mutation carriers and sporadic breast cancer risk协会rad51多态性的dna修复brca1突变携带者和零星的乳腺癌风险.pdf

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association of rad51 polymorphism with dna repair in brca1 mutation carriers and sporadic breast cancer risk协会rad51多态性的dna修复brca1突变携带者和零星的乳腺癌风险

Ricks-Santi et al. BMC Cancer 2011, 11:278 /1471-2407/11/278 RESEARCH ARTICLE Open Access Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk 1,2* 3 4 5 4 4 Luisel J Ricks-Santi , Lara E Sucheston , Yang Yang , Jo L Freudenheim , Claudine J Isaacs , Marc D Schwartz , 4 4 5 5 6 4* Ramona G Dumitrescu , Catalin Marian , Jing Nie , Dominica Vito , Stephen B Edge and Peter G Shields 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 CG genotype (OR