Increased cancer risks for relatives of very early-onset breast cancer cases with and without BRCA1 and BRCA2 mutations

Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Level 1, 723 Swanston Street, Melbourne, Carlton VIC 3053, Australia.
British Journal of Cancer (Impact Factor: 4.84). 09/2010; 103(7):1103-8. DOI: 10.1038/sj.bjc.6605876
Source: PubMed


Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.
We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.
For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57-26.26) and 12.52 (5.21-30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1-49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64-74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91-5.93), 5.25 (2.50-11.01), 7.73 (4.74-12.62), 5.19 (2.33-11.54) and 4.35 (1.81-10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers.
First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations.

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Available from: Graham G Giles
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    • "Mutations were protein-truncating or missense mutations classified as deleterious by the Breast Cancer Information Core (National Human Genome Research Institute, 2002). Details of testing are given elsewhere (Dite et al, 2010). BRCA1 and BRCA2 mutation testing of family members was conducted for 514 of 1857 prevalent cases (28%) identified at baseline, and for 79 of 4176 unaffected participants (2%). "
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