Population-based study of risk of breast cancer in carriers of BRCA2 mutation

Background: Estimates of an 80-90% risk of breast cancer for carriers of germline mutations in the BRCA1 and BRCA2 genes are based on studies of families at high risk of breast cancer. Risk estimates for a population are possible if the mutation status of a representative sample of that population can be assessed. In Iceland, one common founder BRCA2 mutation occurs in 0.6% of the population. Iceland has a population-based cancer registry and a large collection of pedigrees, and estimation of cancer risk in mutation carriers is therefore possible. Methods: We studied 575 breast-cancer patients, 541 women and 34 men unselected for family history of breast cancer. Data on cancer in first-degree relatives were available from the cancer registry. Risk of cancer was estimated by comparing the history of cancer in first-degree relatives of carriers and non-carriers. Findings: 56 (10.4%) of the 541 women and 13 (38%) of the 34 men carried the 999del5 mutation. The estimated risk of breast cancer at age 50 for all female carriers of the 999del5 mutation was 17.0% (95% CI 9.1-25.9) and 37.2% (22.4-53.9) at age 70. Interpretation: The results of our population-based study show that the mean risk of breast cancer in carriers of mutation in BRCA2 is lower than previously suggested. Individual risk assessment will, however, have to take account of family history.