title: The RAD51 135 G>C polymorphism modifies breast cancer and ovarian cancer risk in Polish BRCA1 mutation carriers.
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.
authors.affiliation: Department of Genetics and Pathology, Pomeranian Medical University, Polabska 4, 70-115 Szczecin, Poland. aniaj@sci.pam.szczecin.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Janusz
authors.initials: J
authors.lastname: Menkiszak
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiñski
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic; D051135:Rad51 Recombinase / Q000235:genetics*; D012042:Registries; D012307:Risk Factors; D018709:Statistics, Nonparametric
chemical_list: C495153:RAD51 protein, human; D051135:Rad51 Recombinase