Ovarian Cancer And Ec

Excess ovarian cancers have been associated with familial EC (4,45). In a recent study of 19,175 women with invasive ovarian cancer in the nationwide Swedish Family-Cancer Database, Hemminki and Granstrom calculated standardized incidence ratios (SIRs) for ovarian cancer of 1.45 if mothers had EC and 2.53 when sisters were affected with EC (49). The SIR for endometrioid ovarian carcinoma was 3.40 when mothers had EC. These results confirmed earlier observations by Watson et al. (50), which showed that ovarian cancers associated with HNPCC syndrome were predominantly epithelial tumors with an unusually large proportion being endometrioid and clear cell carcinomas, both of which are histological types that also arise from endometrium (50). In this international collaborative study of women who were known, presumed (based on cancer status), or considered at high-risk (based on pedigree position) to be mutation carriers from HNPCC syndrome families, 94% of the ovarian neoplasms were epithelial tumors (50). Endometrioid (18.3%) and clear cell (9.9%) carcinomas together included 28.2% of the invasive ovarian epithelial cancers in 71 women with recorded histologies (50). These ratios of endometrioid carcinoma or clear cell carcinoma individually and combined, considerably exceeded the 13.2% combined total of endometrioid (9.6%)

and clear cell (3.6%) ovarian carcinomas in general population studies reported from the NIH-SEER program. Also, the 20% combined total of endometrioid (14%) and clear cell (6%) ovarian carcinomas reported by FIGO (51,52). A case-control study by Schildkraut and Thompson (53) of 493 epithelial ovarian cancer cases against 2465 control subjects, found that an increased risk (odds ratio = 2.7, 95%CI = 1-6.9) for endometrioid ovarian carcinoma was associated with family history of EC. Borderline ovarian tumors made up just 4.1% of the epithelial ovarian neoplasms in HNPCC mutation carriers in the international collaborative study compared with 10.4% of the sporadic ovarian neoplasms reported by FIGO (50,52).

Women from HNPCC syndrome kindreds who developed ovarian cancer, were diagnosed at 43 years mean age (50). This was at least 16 years younger than the mean age for the diagnosis of ovarian cancer reported by the NIH-SEER program in the general population of the United States and 13 years younger than the mean age reported by FIGO (51,52). The total proportion (72.2%) of well-differentiated (30.6%) and moderately well-differentiated (41.7%) carcinomas in the international collaborative study of ovarian neoplasms in women from HNPCC syndrome kindreds did not significantly differ from the total proportion (76.6%) of well-differentiated (42.5%) and moderately well-differentiated (34%) carcinomas in the FIGO data (51,53). Most of the ovarian carcinomas diagnosed in HNPCC syndrome kindreds were still confined to the ovary (Stage 1,60.9%) or not extending beyond the gynecological organs and pelvic peritoneum (Stage II, 41.7%) in marked contrast to only 26% Stage I and 10.2% Stage II carcinomas reported by FIGO data (50,52). The relatively earlier age and lower stage of ovarian cancer diagnosis in members of HNPCC syndrome families may reflect a unique genesis of these tumors. Or, on the other hand, these findings might be a result of the early discovery of some unexpected ovarian cancers during surveillance for CRC and EC. Because of known or suspected increased cancer risk or the coincidental finding of early ovarian cancers at the time of therapeutic or prophylactic surgery for CRC and/or EC in the high-risk patients.

The 5-year survival rate for carcinomas that were diagnosed, although still confined to the ovary in women from HNPCC syndrome families (85%) was commensurate with the 5-year survival rate for Stage I cancers in the FIGO data (83%). But, as yet unexplained, women with Stage III ovarian carcinoma from HNPCC syndrome families had better prognosis for 5-year survival (42%) than did women with Stage III ovarian carcinoma patients reported by FIGO (26%) (50). This may simply reflect the small number of patients with ovarian carcinoma (9/64) in the data available to the international collaborative HNPCC study group (50). Or there may have been slightly more favorable tumors by stage, more aggressive treatment, or a younger and more physiologically healthy cohort of ovarian cancer patients diagnosed from HNPCC syndrome families in the collaborative study.

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