Breast Cancer Risk Reduction Associated with the RAD51 Polymorphism among Carriers of the BRCA1 5382insC Mutation in Poland

Breast Cancer Risk Reduction Associated with the RAD51 Polymorphism among Carriers of the BRCA1 5382insC Mutation in Poland1

Hereditary Cancer Centre [J. H., T. B., J. L.,], Department of Genetics and Pathology [A. J., M. M., B. M., B. G., J. L.], Pomeranian Academy of Medicine, Szczecin 70-115, Poland; Centre for Research on Women’s Health, University of Toronto, Ontario, Canada [S. A. N.]; Unit of Genetic Epidemiology, International Agency for Research on Cancer, Lyon, France [D. E. G.]; and Department of Molecular Biology, Inter-University Unit, University of Szczecin and Pomeranian Academy of Medicine, Szczecin, Poland [K. N.]

Abstract

The observed heterogeneity of breast cancer risk among women who carry the same BRCA1 mutation suggests the existence of modifying environmental and genetic factors. The product of the RAD51 gene functions with BRCA1 and BRCA2 in the repair of double-stranded DNA breaks. To establish whether polymorphic variation of RAD51 modifies risk for hereditary breast cancer, we conducted a matched case-control study on 83 pairs of female carriers of the BRCA1 5382insC mutation. Cases consisted of women with breast cancer, and controls were women with the same mutation but who were unaffected. The frequency of the RAD51 135C variant allele was established in cases and controls using RFLP-PCR. The RAD51 135C allele was detected in 37% of unaffected and in 17% of affected BRCA1 carriers. Among 27 discordant matched pairs, the RAD51 135C allele was found in the healthy carrier on 22 occasions and in the affected carrier on only five occasions (odds ratio = 0.23; 95% confidence interval, 0.07–0.62; P = 0.0015). This finding suggests that RAD51 is a genetic modifier of breast cancer risk in BRCA1 carriers in the Polish population. It will be of interest to confirm this in other populations as well.

Footnotes

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↵1 This work was supported by EC Project Grant No. QLRT-1999-00063.
↵2 To whom requests for reprints should be addressed, at Department of Genetics and Pathology, Pomeranian Academy of Medicine, Ul. Połabska 4, Szczecin 70-115, Poland. Phone/Fax: 48-91-466-15-33; E-mail: aniaj{at}sci.pam.szczecin.pl
↵3 The abbreviations used are: OR, odds ratio; CI, confidence interval.
- Accepted February 14, 1903.
- Received August 1, 1902.
- Revision received February 14, 1903.