D302H polymorphism delays the age of onset of breast cancer in and carriers

International audienceThe polymorphic genetic differences among individuals may modify the high risk for breast cancer (BC) and/or ovarian cancer (OC) susceptibility conferred by and mutations. In the present study we investigate the relevance of −135C > G, R72P, * and D302H polymorphisms as potential modifiers of BC and/or OC susceptibility conferred by these mutations. The study group encompasses 390 / mutation carriers (182 affected with BC and/or OC and 208 unaffected) of 131 unrelated families studied in the Program of Genetic Counselling on Cancer of Valencia Community. The polymorphisms were detected in genomic DNA by ASRA method or real time PCR using fluorescently labeled probes. We found similar incidence of −135C > G, R72P and * polymorphisms among affected and unaffected individuals considering / mutations together and separately. However, the D302H polymorphism was strongly associated with the absence of BC [OR = 3.41 (95% CI 1.33–8.78,  = 0.01)]. In fact, in the females with D302H polymorphism the BC appeared at a median age of 58 in opposition to the 47 years observed for the wild type subjects ( = 0.03). Furthermore, the D302H positive females showed a 50% probability of being free of BC by the age of 78 versus the 2% of the negative ones. Our results support that the presence of the D302H polymorphism diminishes the high risk of BC conferred by and mutations, making possible that some of the carriers could escape from suffering BC along their life span