Correlation of breast cancer risk in European BRCA2 mutation carriers with birth cohort.

1537 Background: Mutations in the Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BRCA2) lead to an elevated risk of developing breast (BC) and ovarian cancer (OC). However, risk estimates vary, depending on the study population. Furthermore, there are indications that birth cohort can influence the cancer risk. We investigated the risks for BC and OC associated with BRCA2 mutations in a cohort of female mutation carriers of a genetically heterogeneous central European population who were identified by molecular genetic testing in our institute. Methods: This study included 171 Caucasian women from Austria who underwent genetic counseling and where molecular genetic analysis identified a mutation in the BRCA2 gene at the Medical University of Vienna, Division of Senology, in Austria. A total of 57 healthy and 114 affected BRCA2-carriers were detected. The risk was estimated using the product limit method. The log rank test was used to compare different strata. Results: The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 77–93%) and 31% for OC (95% CI 16–46%) in our BRCA2 study population. Female BRCA2-carriers born in 1958 or later were at a significantly higher risk of developing BC (p<0.001; 88% vs. 46% to age 40) but not of OC (p is not significant; 0% vs. 2% to age 40) compared to mutation carriers born earlier. Conclusions: We conclude that female BRCA2 mutation carriers should also be counseled about their cohort-dependent cancer risk, especially for breast cancer. Further research about variables that may affect cancer risk like lifestyle-related factors should be considered.