The presence of hereditary BRCAJ gene mutations in women with familial breast or ovarian cancer and the frequency of occurrence of these tumours in their relatives

In 48 women with familial breast cancer as well as in 22 women with familial ovarian cancer, the presence of pathogenic mutations in BRCA1 gene were found in 35.4% and 54.6% of patients, respectively. From the patients with mutations we created two groups: the CaM--probands with breast cancer and CaOv--probands with ovarian cancer. The probands with breast cancer were younger by a mean of five years than the probands with ovarian cancer (p = 0.048).

Methods: The PCR-SSCP procedure was used to find mutations in the BRCA1 gene. Fragments suspected of mutation were subjected to nucleotide sequencing.

Results: In the CaM group, which consisted of 17 women with breast cancer, the following mutations in the BRCA1 gene were detected: 5382insC, T300G, 3819del5 and IVS20+60ins12. The probands of the CaM group and their relatives developed a total of 49 breast and ovarian cancers. Among all these tumours the breast cancers of the probands made up 34.7%, the breast cancers of proband relatives made up 57.1% and the ovarian cancers of probands and their relatives made up only 8.2%. The CaOv group consisted of 12 probands with ovarian cancers in whom we detected only two kinds of mutations: 5382insC and 185delAG. The probands of the CaOv group and their relatives developed a total of 38 ovarian and breast cancers. Among all these tumours the ovarian cancers of the probands made up 31.6%, the ovarian cancers of their relatives made up 34.2% and the breast cancers of the relatives 34.2% of tumours. In the probands with breast or ovarian cancer the predominant mutation was 5382insC--in the BRCA1 gene detected in 76.5%, and 91.7%, respectively. Despite the predominant presence of the same mutation in probands from both groups the ratio of the number of breast cancers to the number of ovarian cancers in their relatives differed significantly (p = 0.0003).

Conclusion: This data shows that the presence of the 5382insC mutation in the BRCA1 gene is not always associated with the development of ovarian cancer. It is very likely that the development of ovarian cancer requires some additional factor, which was common among the familial ovarian cancer patients, and was almost inexistent among the familial breast cancer patients. On the other hand, the development of ovarian cancer at a later age than breast cancer in probands suggests that some factors exist which slow down the development of ovarian cancer or which accelerate the development of breast cancer.

BRCAJ gene mutation; Familial breast cancer; Familial ovarian cancer

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