Fact Sheets

Endometrial cancer

Issue: Endogenous and exogenous estrogens are important in the development of endometrial cancers.

Background: Endometrial cancer usually occurs between the ages of 50 and 65 years, and is rare before the age of 40. Endometrial cancer is the most common malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of endometrial cancer exist. Type I tumors occur more frequently, are estrogen-dependent and are associated with postmenopausal hormone replacement therapy (HRT) and tamoxifen. Continued exposure to estrogens unopposed by progesterone is a known risk factor for endometrial cancer, as is excess body weight. In addition to the possible effect on the development and continuation of obesity, diet may exert effects on the endogenous hormonal milieu, thus influencing development of this cancer. This type of cancer appear to develop through a series of precursor lesions including simple, complex and atypical hyperplasia. They generally have a good prognosis. Endometrial cancer type II is estrogen-independent, occurs among elderly women, and have a poor prognosis. The concern that environmental organochlorine pollutants may cause cancer in humans is widespread and has been tested almost exclusively in epidemiological studies of breast cancer.

Trends: Endometrial cancer ranks fourth in terms of cancer occurrence and eighth in terms of age-adjusted mortality in women. In the most industrialized countries, annual incidence rates are about 10 per 100,000 women in UK, Spain, and France and 25 per 100,000 women in USA and Canada. In 1999, in the USA, there were about 37,400 new cases or about 6% of all incident cancers. The mortality rates for this cancer have declined about 60% since the 1950s. Although, endometrial cancer incidence showed a marked increase in the early 1970s, followed by a reduction in the 1980s, and back to previous levels. But since the 1980 the incidence has remained steady.

Consistency of the data: Environmental pollutants such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) may increase breast cancer risk partially through estrogenic activity. The association between HRT and endometrial cancer is much stronger than that between HRT and breast cancer. Therefore, one might plausibly expect that any carcinogenicity of organochlorine compounds would be easier to detect in endometrial than breast cancer. Unfortunately, there are few epidemiologic studies on this subject. In a population-based case-control study in Sweden (Weiderpass et al., 2000), serum levels of 10 chlorinated pesticides and 10 PCB congeners were measured. There were no significant associations between pesticide or PCB levels and endometrial cancer risk. To date, only one study has addressed the association between organochlorine pesticides and PCBs and the risk of endometrial cancer, and the results were negative (Sturgeon et al., 1998).

Experimental evidence: The estrogenicity of pesticide and PCBs has been noted in some animal studies. In one study, p, p'-DDT, the active pesticide, was active on uterine enzyme activities, as well as an edematous response in deep and superficial endometrium of immature female Sprague Dawley rats. In another study, o, p'-DDT has been associated with effects on hormones and reproductive behavior that imply estrogenic potency of this compound. In ovariectomized rats, it caused estrogenic responses in the endometrium. Thus, according to animal studies, the DDT and PCBs class of compound can bind to estrogen receptors. In addition to the estrogenic effects of PCBs, several PCB congeners exhibit antiestrogenic activity in vitro and in vivo. However there was no evidence of an association between environmental toxicant exposure and endometrial cancer in all animal studies conducted.

Biological plausibility: Analysis of the incidence of endometrial cancer should be the most informative with respect to a hormonal active agent effects, because the lining of the uterus (endometrium) is an exquisitely sensitive tissue both to estrogenic and to antiestrogenic effects in women.

Conclusion: The hypothesis that human exposure to environmental agents with estrogenic activity may cause endometrial cancer is not supported by animal studies and the very few epidemiological studies conducted to date. Nevertheless, it can not be conclusively rejected on the basis of available data.