Obesity Epidemiology

198 EPIDEMIOLOGIC STUDIES OF CONSEQUENCES OF OBESITYObesity-Related CancersEndometrial cancer (cancer of the uterine lining) was the first cancer to be recognized asbeing obesity related. There is convincing and consistent evidence from both case-controland cohort studies that overweight and obesity are associated strongly with endometrialcancer. 2,3 A linear increase in the risk of endometrial cancer with increasing weight orbody mass index (BMI) has been observed in most studies. 1,3,6,10-13 The increase in riskgenerally ranges from 2- to 3.5-fold in overweight and/or obese women (Table 10.2), andmight be somewhat higher in studies of mortality than incidence.The probable mechanism for the increase in risk of endometrial cancer associatedwith obesity in postmenopausal women is the obesity-related increase in circulatingestrogens. 2,3 Many studies have shown large increases in endometrial cancer risk amongpostmenopausal women who take unopposed estrogen replacement therapy (i.e., estrogenin the absence of progesterone), as well as increases in risk among women with highercirculating levels of total and bioavailable estrogens. In premenopausal women, endometrialcancer risk is also increased among women with polycystic ovary syndrome, whichis characterized by chronic hyperinsulinemia as well as progesterone deficiency. Thus, inboth pre- and postmenopausal women, endometrial cancer is increased by the mitogeniceffects of estrogens on the endometrium when these effects are not counterbalanced bysufficient levels of progesterone.Mechanisms involving the insulin pathway may also play a role in endometrial cancer.Blood levels of adiponectin, an insulin-sensitizing protein, secreted exclusively by adipocytesare lower in obese individuals and those with insulin-resistant conditions, 14 andare inversely associated with endometrial cancer independent of BMI. 15,16 This is entirelyconsistent with studies showing a positive association between type 2 diabetes and endometrialcancer, 2 and another showing upper body fat to be significantly associated withTable 10.2 Relative Risks Associated with Overweight and Obesity and the Percentage ofCases Attributable to Overweight and Obesity in the United StatesRelative Risk*BMIType of Cancer ≥25-