Diabetes, physical activity and endometrial cancer

Abstract

Accumulating evidence suggests that hyperinsulinemia, in the context of insulin resistance, is associated with carcinogenesis. Physical activity is involved in the regulation of metabolic and hormonal pathways and is an important factor affecting hyperinsulinemia, insulin resistance and body weight. The major modifiable determinants of insulin resistance, hyperinsulinemia, and diabetes such as obesity, and physical activity, have also been shown to be risk factors for endometrial cancer. No previous studies have investigated whether physical inactivity is a modifier of the association between diabetes and risk of endometrial cancer. No previous study has evaluated a combined effect of diabetes, obesity and physical inactivity as a predictor of endometrial cancer risk. No previous meta-analysis of diabetes and endometrial cancer risk has been performed. Moreover no previous study has investigated the effect of leisure time physical inactivity directly on endometrial cancer risk.

We examined the association between diabetes and incidence of endometrial cancer in the Swedish Mammography Cohort. Given that the effect of diabetes may vary by risk factors for endometrial cancer we also examined the potential effect modification by obesity and physical activity. In this population-based prospective cohort of 36 773 women, 225 incident endometrial adenocarcinoma cases were diagnosed between 1997 and 2005. The relative risk (RR) for endometrial cancer among women with diabetes compared to non diabetic women was 1.94, 95% CI =1.23 to 3.08. Obese diabetics with low physical activity had a RR = 9.61, 95% CI=4.66 to 19.83, compared to non-obese, non-diabetic women with high physical activity.

We performed a meta-analysis on diabetes and endometrial cancer, we identified 16 studies (3 cohort and 13 case-control studies), and found that diabetes was statistically significantly associated with an increased risk of endometrial cancer incidence, (summary RR = 2.10 95% CI= 1.75-2.53). Analysis of 2 studies of mortality found a summary RR= 1.58 95% CI 0.94-2.66 for diabetes and endometrial cancer mortality.

We investigated the association of total physical activity and different types of physical activity with risk of endometrial cancer in the Swedish Mammography Cohort. After exclusions due to some missing physical activity estimates 33 723 women and 199 endometrial cancer cases were included in the analysis. Relative risks (RR) for endometrial cancer comparing the second to fourth quartiles of total physical activity to the lowest one were 0.80 (95% CI 0.541.18); 0.87 (95% CI 0.59-1.28); 0.79 (95% CI 0.53-1.17) respectively. High leisure time inactivity (watching TV/sitting 5 hours or more a day) compared to low was associated with increased risk of endometrial cancer RR=1.66 (95% CI 1.05-2.61).

We observed a statistically significant association between diabetes and endometrial cancer in our cohort. Results from the meta-analysis support a relationship between diabetes and increased risk of endometrial cancer incidence. The similar point estimates from the cohort analysis and metaanalysis suggest that diabetes may be associated with a two-fold increased risk of endometrial cancer. Total physical activity was only weakly associated with a decreased risk of endometrial cancer, although leisure time inactivity was statistically significantly associated with increased risk for endometrial cancer. These findings support general health recommendations to reduce obesity and increase physical activity.