Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk

BMC Cancer

Research Article

Lara E Sucheston¹  Jo L Freudenheim²  Dominica Vito²  Jing Nie²  Stephen B Edge³  Luisel J Ricks-Santi⁴  Yang Yang⁵  Catalin Marian⁵  Claudine J Isaacs⁵  Marc D Schwartz⁵  Peter G Shields⁵  Ramona G Dumitrescu⁵ 

[1] Department of Biostatistics, University at Buffalo, State University of New York, 14214, Buffalo, NY, USA;Department of Social and Preventive Medicine, University at Buffalo, State University of New York, 14214, Buffalo, NY, USA;Department of Surgery, University at Buffalo, State University of New York, 14214, Buffalo, NY, USA;Howard University Cancer Center, 2041 Georgia Ave, 20060, NW Washington, DC, USA;National Human Genome Center at Howard University, 2041 Georgia Ave, NW #615, 20059, Washington, DC, USA;Lombardi Comprehensive Cancer Center, Georgetown University Medical Cancer, 3800 Reservoir Rd, NW, 20057, Washington, DC, USA;

关键词: Breast Cancer Risk;    Mutation Carrier;    BRCA1 Mutation;    BRCA1 Mutation Carrier;    Sporadic Breast Cancer;   

DOI  :  10.1186/1471-2407-11-278

 received in 2011-01-06, accepted in 2011-06-27,  发布年份 2011

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Ricks-Santi et al; licensee BioMed Central Ltd. 2011