Cholecystectomy and endometrial cancer: a marker of long-term elevated estrogen exposure?

Excess hormones, both endogenous and exogenous, are implicated in the etiology of endometrial cancer. We considered whether having had gallstones or a cholecystectomy (surgery to remove the gallbladder), which are more common in women who are obese and who use exogenous hormones, might be a marker for high lifetime levels of estrogen. We conducted a population-based study of endometrial cancer cases and community controls in women aged 40-79 years. Participants completed an interviewer-administered questionnaire that elicited exposures prior to diagnosis or reference date, including history of gallstones and cholecystectomy, as well as reproductive history, lifetime body mass, smoking, postmenopausal hormone (PMH) use, and other risk factors. Compared to controls, cholecystectomy was associated with a 50% increased risk of developing endometrial cancer (odds ratio = 1.5 [1.1-2.0]). The relationship appeared to depend upon PMH user status; the association was observed only among never hormone users. Body mass index did not appear to modify this relationship. Having a diagnosis of gallstones was also associated with endometrial cancer, although to a lesser magnitude. Although other etiologic factors may play a role in the relation between cholecystectomy and endometrial cancer, the current analysis suggests that this association is attributable, at least in part, to the sharing of hormonal risk factors.