alexa Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program.
Genetics & Molecular Biology

Genetics & Molecular Biology

Hereditary Genetics: Current Research

Author(s): Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL,

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Abstract BACKGROUND: Increasing numbers of BRCA1 mutation carriers are being identified in cancer risk evaluation programs. However, no estimates of cancer risk specific to a clinic-based population of mutation carriers are available. These data are clinically relevant, because estimates based on families ascertained for linkage studies may overestimate cancer risk in mutation carriers, and population-based series may underestimate it. Wide variation in risk estimates from these disparate ascertainment groups makes counseling in risk evaluation programs difficult. The purpose of this study was to estimate BRCA1-related cancer risks for individuals ascertained in a breast cancer risk evaluation clinic. METHODS: Cumulative observed and age-adjusted cancer risk estimates were determined by analyzing 483 BRCA1 mutation carriers in 147 families identified in two academic breast and ovarian cancer risk evaluation clinics. Cancer risks were computed from the proportion of individuals diagnosed with cancer during a 10-year age interval from among the total number of individuals alive and cancer-free at the beginning of that interval. Age-of-diagnosis comparisons were made using two-sided Student's t tests. RESULTS: By age 70, female breast cancer risk was 72.8\% (95\% confidence interval [CI] = 67.9\% to 77.7\%) and ovarian cancer risk was 40.7\% (95\% CI = 35.7\% to 45.6\%). The risk for a second primary breast cancer by age 70 was 40.5\% (95\% CI = 34.1\% to 47.0\%). We also identified an increased risk of cancer of the colon (twofold), pancreas (threefold), stomach (fourfold), and fallopian tube (120-fold) in BRCA1 mutation carriers as compared with Surveillance, Epidemiology, and End Results (SEER) Program population-based estimates. CONCLUSION: The estimates for breast and ovarian cancer risk in BRCA1 mutation carriers is higher than population-based estimates but lower than estimates based on families ascertained for linkage studies. These cancer risk estimates may most closely approximate those faced by BRCA1 mutation carriers identified in risk evaluation clinics.
This article was published in J Natl Cancer Inst and referenced in Hereditary Genetics: Current Research

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