There is increasing evidence that hereditary factors play a greater role in ovarian cancer than in any of the other common cancers of adulthood. This is attributable, to a large extent, to a high frequency of mutations in the BRCA1 or BRCA2 genes. In Poland, 3 common founder mutations in BRCA1 account for the majority of families with identified BRCA mutations. Our study was conducted in order to estimate the prevalence of any of 3 founder BRCA1 mutations (5382insC, C61G and 4153delA) in 364 unselected women with ovarian cancer, and among 177 women with ovarian cancer and a family history of breast or ovarian cancer. A mutation was identified in 49 out of 364 unselected women with ovarian cancer (13.5%) and in 58 of 177 women with familial ovarian cancer (32.8%). The majority of women with ovarian cancer and a BRCA1 mutation have no family history of breast or ovarian cancer. The high frequency of BRCA1 mutations in Polish women with ovarian cancer supports the recommendation that all Polish women with ovarian cancer should be offered testing for genetic susceptibility, and that counseling services be made available to them and to their relatives. It is important that mutation surveys be conducted in other countries prior to the introduction of national genetic screening programs.
This study was undertaken with regard to the gonadotropin theory of ovarian cancer advocated in the literature and was designed to disclose specific features of ovarian morphology in carriers of the BRCA1 gene mutation. We enrolled 171 patients and divided them into two groups: A (n=90)--operated for breast cancer (30 patients with and 60 without the BRCA1 mutation); B (n=81)--with the BRCA1 mutation qualified for preventive adnexectomy. According to the authors' classification described herein, some patients without the BRCA1 mutation retained "signs of estrogenization" in menopausal ovaries, revealing the role of estrogens as a factor promoting mammary carcinogenesis in these patients. A tendency to premature menopause was observed in BRCA1 mutation carriers of groups A and B as evidenced by the final menorrhea appearing at a younger age and almost total absence of "signs of estrogenization" in menopausal ovaries. It is concluded from these findings that earlier menopause in carriers of the BRCA1 mutation is associated with hypergonadotropic activity and may predispose to ovarian cancer at younger age.
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