Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors.

OBJECTIVE: To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas.

METHODS: A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors.

RESULTS: Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2).

CONCLUSION: Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar.