Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases

It is estimated that about 5–10% of ovarian and 2–5% of all breast cancer patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on the basis of family history of breast or ovarian cancers. The purpose of our study was to establish the frequency of positive family history of cancer in a series of Polish consecutive breast and ovarian cancer patients in two groups, with and without the BRCA1 gene mutations. We analysed the prevalence of four of the most common BRCA1 mutations: 5382insC (c.5266dupC), 300T>G (p.181T>G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5). The patient group consisted of 1,845 consecutive female breast and 363 ovarian cancer cases. 19 out of 37 (51%) of BRCA1-positive ovarian cancer patients and 21 out of 55 (39%) BRCA1-positive breast cancer had negative family history of breast and/or ovarian cancer among first- and second-degree relatives. In ovarian cancer patients, negative family history was more frequent in those with 300T>G BRCA1 gene mutation than in 5382insC carriers. This finding indicates the necessity of searching for 300T>G mutation in families with a single diagnosis of ovarian cancer in family. The high frequency of mutations detected in breast cancer patients lacking obvious family history shows that breast cancer patients should be qualified for genetic testing on the basis of wide clinical and pathological criteria.