Diabetes and Risk of Endometrial Cancer: A Population-Based Prospective Cohort Study

Abstract

Although there is accumulating evidence that hyperinsulinemia in the context of insulin resistance is associated with carcinogenesis, only one prospective study of endometrial cancer incidence, in relation to diabetes, addressed this issue and showed no significant positive association. No previous study has investigated whether physical activity can modify the association between diabetes and endometrial cancer. We examined the association between diabetes and incidence of endometrial cancer and the potential effect modification by obesity and physical activity in the Swedish Mammography Cohort, a prospective cohort of 36,773 women, including 225 incident endometrial adenocarcinoma cases. After adjustments, the relative risk (RR) for endometrial cancer among women with diabetes comparing with nondiabetic women was 1.94 [95% confidence interval (95% CI), 1.23-3.08].Among obese diabetics, the RR was 6.39 (95% CI, 3.28-12.06) compared with nonobese nondiabetic women. Among diabetics with low physical activity, the RR for endometrial cancer was 2.80 (95% CI, 1.62-4.85) compared with physically active nondiabetic women. Obese diabetics with low physical activity had a RR of 9.61 (95% CI, 4.66-19.83) compared with normal weight nondiabetic women with high physical activity. Diabetes was associated with a 2-fold increased risk, and combination of diabetes with obesity and low physical activity was associated with a further increased risk for endometrial cancer. Interventions to reduce body weight and increase physical activity may have important implications in terms of prevention of endometrial cancer and future management of diabetic subjects. (Cancer Epidemiol Biomarkers Prev 2007;16(2):276 -80)

Diabetes and endometrial cancer: effect modification by body weight, physical activity and hypertension

“…In a Swedish cohort study of 225 cases of endometrial cancer, the relative risk was 2.7 for diabetic women reporting low physical activity and 1.1 among those reporting high physical activity (Friberg et al, 2007). In an Italian case -control study, the association with diabetes was of similar magnitude in women with or without hypertension (Parazzini et al, 1999).…”

“…Diabetes shows a supramultiplicative effect with body mass index, but not with physical activity or hypertension. An increased risk of endometrial cancer in diabetic women has often been reported (Parazzini et al, 1991(Parazzini et al, , 1999Brinton et al, 1992;La Vecchia et al, 1994;Shoff and Newcomb, 1998;Salazar-Martinez et al, 2000;Weiderpass et al, 2000;Anderson et al, 2001;Sharma et al, 2001;Cook et al, 2006;Friberg et al, 2007). Overweight and obesity are major risk factors for both conditions since they are related to increased endogenous oestrogen levels (Parazzini et al, 1991;Calle et al, 2003;Cook et al, 2006).…”

“…Overweight and obesity are major risk factors for both conditions since they are related to increased endogenous oestrogen levels (Parazzini et al, 1991;Calle et al, 2003;Cook et al, 2006). Although the association between diabetes and endometrial cancer may be partly or largely accounted for by the higher body weight of endometrial cancer cases, it has been found to persist after adjustment for body mass index (BMI) (Brinton et al, 1992;La Vecchia et al, 1994;Parazzini et al, 1999;Salazar-Martinez et al, 2000;Friberg et al, 2007).A few of the above studies have investigated the combined role of diabetes and BMI on risk, finding a higher risk among obese diabetic women, most of these, but not all (Anderson et al, 2001), reporting some excess risk also among non-overweight diabetic women.Diabetes is associated with hypertension and physical inactivity, which in turn have been related to endometrial cancer risk (Parazzini et al, 1999; Cust et al, 2007;Voskuil et al, 2007). In a Swedish cohort study of 225 cases of endometrial cancer, the relative risk was 2.7 for diabetic women reporting low physical activity and 1.1 among those reporting high physical activity (Friberg et al, 2007).…”

“…Although the association between diabetes and endometrial cancer may be partly or largely accounted for by the higher body weight of endometrial cancer cases, it has been found to persist after adjustment for body mass index (BMI) (Brinton et al, 1992;La Vecchia et al, 1994;Parazzini et al, 1999;Salazar-Martinez et al, 2000;Friberg et al, 2007).…”

“…Overweight and obesity are major risk factors for both conditions since they are related to increased endogenous oestrogen levels (Parazzini et al, 1991;Calle et al, 2003;Cook et al, 2006). Although the association between diabetes and endometrial cancer may be partly or largely accounted for by the higher body weight of endometrial cancer cases, it has been found to persist after adjustment for body mass index (BMI) (Brinton et al, 1992;La Vecchia et al, 1994;Parazzini et al, 1999;Salazar-Martinez et al, 2000;Friberg et al, 2007).…”