Risk of Cancer in BRCA1 and BRCA2 Mutation-Positive and -Negative Breast Cancer Families (Finland)

Objectives: To compare the risk of cancer between BRCA1 or BRCA2 mutation-positive and -negative families. Methods: We assessed standardized incidence ratios (SIR) in 107 Finnish breast cancer families (12 BRCA1, 11 BRCA2, 84 non-BRCA1/2) with confirmed genealogy. The observed numbers of cancer cases were compared to the expected ones; both numbers were based on the population-based Finnish Cancer Registry. Results: Risk of ovarian cancer for first-degree relatives was high in BRCA1 (SIR 29, 95% confidence interval 9.4-68) and in BRCA2 families (SIR 18, 8.3-35), but not increased for non-BRCA1/2 families (SIR 1.0, 0.2-2.9). The SIR for subsequent ovarian cancer among breast cancer patients was 61 (20-142), 38 (11-98), and 0 (0-4.2), respectively. The risk of subsequent new breast cancer among breast cancer patients was equally high in BRCA1 families (SIR 11, 3.6-26) and in BRCA2 families (SIR 10, 3.3-24) and somewhat lower in mutation-negative families (SIR 3.7, 2.1-6.1). The risk of breast cancer among relatives was markedly increased in all three groups. The only elevated SIR, besides breast and ovarian, was that for prostate cancer in BRCA2 families (SIR 4.9, 1.8-11). Conclusions: The excess risk of breast cancer in non-BRCA1/2 families suggests the existence of another predisposition gene which seems not to be linked with increased risk of ovarian cancer.