In a case-control study to evaluate risk factors for endometrial cancer in Italy, use of noncontraceptive estrogens was associated with a moderately increased risk, whereas obesity appeared to be the most important single risk factor related to cancer of the endometrium. This report considers the estrogen and obesity-related relative risks with regard to various prognostic features of tumors (clinical stage, histologic grade, extent of myometrial invasion, lymph node involvement). In both estrogen users and obese women, the increase in relative risk was greater for earlier than for more advanced tumors. These findings, therefore, provide further support for a specific role of both exogenous and endogenous estrogens in endometrial cancer.
PIP: A previous study by the same authors showed that obesity rather than treatment with noncontraceptive estrogen, was the most important single risk factor related to endometrial cancer. This study investigates the determinants of endometrial cancer by analyzing how the obesity risk and the estrogen risk vary according to various prognostic features of the tumor. 173 women aged 33-84 with a histologically confirmed diagnosis of endometrial cancer were observed and compared to 347 control subjects, aged 33-82, with diseases other than malignant, hormonal, or gynecologic disorders. Complete medical histories were elicited. An estrogen user was defined as a woman with a history of 3 or more months of regular use of noncontraceptive estrogen. Obese women were defined as those with a W/H2 index of 25 or more. Noncontraceptive estrogens were taken by 31% of case subjects and 17% of controls; longterm use was uncommon; estrogen users were younger than nonusers; 49% of users and 63% of nonusers were obese. The estimated relative risk for estrogen use was higher in Stage 1 tumors, in well differentiated tumors, in tumors not infiltrating the myometrium, and in the absence of lymph node involvement. Long discontinued use of estrogen was associated with a lower relative risk than recent use; however, increased likelihood of earlier cancer in estrogen users was evident in both groups. Obesity was present in 63% of case subjects, and 35% of controls; obese women were older than nonobese. Obesity-related risk was increased in the same prognostic features than for estrogen-related risk, but the odds ratios were significantly higher. These data, while confirming the results of the previous study, show that obese women have a pattern of risk similar to that of estrogen users when related to tumor prognostic factors. These results may support the role of both endogenous and exogenous estrogen in endometrial cancer; in fact, obesity may increase the risk of endometrial cancer through an increase of endogenous estrogens as a result of various mechanisms linked to obesity itself. Further studies are needed.