Abstract
We investigated the prevalence of germline BRCA mutations in a population‐based cohort of Austrian women diagnosed with ovarian cancer and its association with family history of cancer. We prospectively collected family pedigrees of 443 Austrian ovarian cancer patients who had been tested for the presence of a germline BRCA or 2 mutations and correlated the familial breast and ovarian cancer burden with the prevalence of BRCA mutations and disease onset. The probability of carrying a gBRCA mutation in patients without family history of cancer is 14% (95% CI 9%‐22%), as opposed to 45% (95% CI 31%‐59%) of patients with at least one family member with ovarian cancer, and 47% (95% CI 40%‐54%) if other relatives have developed breast cancer. If both breast and ovarian cancer are diagnosed in the family, the probability of carrying a germline BRCA1 or 2 mutations is 60% (95% CI 50%‐68%). germline BRCA1 or mutations in families with ovarian cancer only are commonly located in the Ovarian Cancer Cluster Regions when compared to families with both breast and ovarian cancer (P = 0.001, and P = 0.020, respectively). While gBRCA mutation carriers with ovarian cancer do not have a significantly different age at onset than patients with a family history of cancer, gBRCA1 carriers in general have an earlier onset than gBRCA2 carriers (P = 0.002) and patients without a mutation (P = 0.006). The rate of germline BRCA1 or 2 mutations in ovarian cancer patients without a family history or breast or ovarian cancer is low. However, in women with additional family members affected, the prevalence is considerably higher than previously reported.
Highlights
Germline mutations of BRCA1 and BRCA2 confer a high life‐time risk of developing breast (BC) and ovarian (OC) cancer.[1,2] Following an autosomal dominant pattern of inheritance, they are passed on to subsequent generations with a probability of 50% and result in familial aggregation of disease
We looked at the prevalence of germline BRCA1 or 2 mutations in ovarian cancer patients without any family member affected by OC or BC
In OC patients with at least one BC diagnosed in the family, significantly fewer mutations (40/119; 34%, 95% Confidence Interval (CI) 26%‐42%) were located in the BRCA1 OC cluster regions (OCCRs) (P = 0.001; Chi Square test)
Summary
Germline mutations of BRCA1 and BRCA2 confer a high life‐time risk of developing breast (BC) and ovarian (OC) cancer.[1,2] Following an autosomal dominant pattern of inheritance, they are passed on to subsequent generations with a probability of 50% and result in familial aggregation of disease. While traditionally BRCA mutation analysis has been limited to OC patients with a significant family history of cancer, the availability of PARP inhibitors and its efficacy in platin‐sensitive recurrent OC in women with BRCA1 and BRCA2 mutations mandates testing of women with epithelial OC.[8,9]. This strategy is supported by national and international guidelines.[10]. Patients were prospectively followed up for incident familial breast and ovarian cancer cases In this cohort, we have evaluated the age of disease onset in mutation carriers in relation to their family history and compared it to women with no germline mutation
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