The RAD51 135 G>C Polymorphism Modifies Breast Cancer and Ovarian Cancer Risk in Polish BRCA1 Mutation Carriers
- Anna Jakubowska1,3,
- Jacek Gronwald1,
- Janusz Menkiszak2,
- Bohdan Górski1,
- Tomasz Huzarski1,
- Tomasz Byrski1,
- Lutz Edler4,
- Jan Lubiñski1,
- Rodney J. Scott5 and
- Ute Hamann3
- Departments of 1Genetics and Pathology, and 2Surgical Gynecology and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland; 3Division of Molecular Genome Analysis and 4Central Unit Biostatistics, German Cancer Research Center, Heidelberg, Germany; and 5Discipline of Medical Genetics, School of Biomedical Sciences, University of Newcastle, and The Hunter Medical Research Institute, Newcastle, New South Wales, Australia
- Requests for reprints:
Anna Jakubowska, Department of Genetics and Pathology, Pomeranian Medical University, Polabska 4, 70-115 Szczecin, Poland. Phone: 48-91-48-22-15-32; Fax: 48-91-48-22-15-33. E-mail: aniaj{at}sci.pam.szczecin.pl
Abstract
Breast and ovarian cancer penetrance in BRCA1 mutation carriers is estimated to be between 15% and 80% by age 70 years. At present, it is not possible to predict with any certainty who is most likely to develop disease or which age it will develop. Previous studies have tried to correlate the sites of BRCA1 mutations with disease risk; however, the results have not yielded any definitive association. An alternative explanation that could account for differences in the penetrance of BRCA1 mutations is the action of modifier genes. In this study, we have investigated the role of the RAD51_135_G>C polymorphism in breast and ovarian cancer case-control populations of Polish women who have been matched for BRCA1 mutation and year of birth. The results reveal that women who harbor the C allele have almost twice the reduction in breast and ovarian cancer risk compared with women who harbor only the G allele. These findings suggest that the effect of the RAD51 C allele is an important risk modifier for malignancies occurring on a background of BRCA1 mutations. In addition, we were able to show that the site of the BRCA1 mutation does not influence the effect of the RAD51 C allele, indicating that this polymorphism contributes to prevention of disease in BRCA1 carriers. In conclusion, the RAD51 C allele seems to protect against both breast and ovarian cancer in women harboring BRCA1 mutations. (Cancer Epidemiol Biomarkers Prev 2007;16(2):270–5)
Footnotes
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Grant support: Deutsches Krebsforschungszentrum, Heidelberg (supported the work and provided a fellowship grant to A. Jakubowska), and Yamagiwa-Yoshida Memorial Unio Internationale Contra Cancrum International Cancer Study Grant (A. Jakubowska and J. Gronwald).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: A. Jakubowska is a guest researcher from the Pomeranian Medical University, Szczecin, Poland.
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- Accepted December 5, 2006.
- Received July 7, 2006.
- Revision received October 10, 2006.
