BRCA germline mutations in Jewish women with uterine serous papillary carcinoma

Shaare Zedek Medical Center, Yerushalayim, Jerusalem, Israel
Gynecologic Oncology (Impact Factor: 3.77). 03/2004; 92(2):521-4. DOI: 10.1016/j.ygyno.2003.11.009
Source: PubMed


Our recent study determined the possible effects and incidence of BRCA1 and BRCA2 germline mutations in uterine serous papillary carcinoma (USPC). The purpose of this study was to determine the incidence of these mutations in an enlarged series of USPC.
We screened DNA from 27 women with USPC for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1-185delAG and 5382 insC,BRCA2-6174delT). In women with germline mutations, tumor DNA was screened for loss of heterozygosity (LOH) at the appropriate loci.
Women (20) were of Jewish Ashkenazi origin and seven were non-Ashkenazi. Four of 20 (20%) Ashkenazi women were carriers of germline mutations: three 185delAG mutation and one 5382insC mutation. All carriers had strong family histories of breast-ovarian carcinoma. Seven out of 20 (35%) women had been diagnosed for breast carcinoma before diagnosis of USPC. Family histories of 12 women (60%) showed at least one first-degree relative with breast, ovarian, or colon carcinoma. Loss of heterozygosity analysis found a loss of the wild-type BRCA1 allele in three of the four primary uterine tumors that were examined.
Our findings further support our previous published data suggesting a high incidence of BRCA carriers among USPC Ashkenazi Jewish patients. The loss of heterozygosity in the tumor tissue of carriers coupled with the high frequency of patient and family history of breast and ovarian malignancies suggest that USPC might be part of the manifestation of familial breast-ovarian cancer in Ashkenazi Jewish patients.

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    • "So not only does the finding of asymptomatic occult endometrioid endometrial carcinomas, particularly in patients who have received tamoxifen, have implications in managing women at hereditary risk for HBOC, but even more significant may be the possibility that endometrium, as well as ovarian fallopian tube epithelium, might be a site of primary transformation to serous carcinoma in carriers of cancer-associated BRCA1 and BRCA2 mutations (Casey and Bewtra, 2004). Apropos our observations, Hornreich et al. (1999) reported a case of uterine serous papillary carcinoma in an Israeli woman who carried the same Ashkenazi germline BRCA1 mutation as her sister who also was diagnosed with ovarian papillary serous carcinoma, and subsequently this group found that BRCA1 mutations were carried by 4 of their 20 patients (20%) with papillary serous uterine carcinoma (Lavie et al., 2004). Ashkenazi BRCA1 or BRCA2 founder mutations were found in 7/22 (32%) consecutive cases of papillary serous uterine carcinoma in Jewish women studied by Biron-Shental et al. (2006). "
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    • "cervical cancer RR = 3.72, 95% CI 2.26-6.10) [12,13]. Even though early detection of these cancers is often possible, women already planning to undergo BRRO may consider whether they wish to eliminate uterine and cervical cancer risks by undergoing TAH at the time of their BRRO. "
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