Open Access Highly Accessed Research article

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

Luisel J Ricks-Santi12*, Lara E Sucheston3, Yang Yang4, Jo L Freudenheim5, Claudine J Isaacs4, Marc D Schwartz4, Ramona G Dumitrescu4, Catalin Marian4, Jing Nie5, Dominica Vito5, Stephen B Edge6 and Peter G Shields4*

Author Affiliations

1 Howard University Cancer Center, 2041 Georgia Ave, NW Washington, DC 20060, USA

2 National Human Genome Center at Howard University, 2041 Georgia Ave, NW #615, Washington, DC 20059, USA

3 Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, NY 14214, USA

4 Lombardi Comprehensive Cancer Center, Georgetown University Medical Cancer, 3800 Reservoir Rd, NW, Washington, DC 20057, USA

5 Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, NY 14214, USA

6 Department of Surgery, University at Buffalo, State University of New York, Buffalo, NY 14214, USA

For all author emails, please log on.

BMC Cancer 2011, 11:278  doi:10.1186/1471-2407-11-278

Published: 27 June 2011



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.


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.