Leisure-time physical activity and endometrial cancer risk: Dose-response meta-analysis of epidemiological studies

Although considerable evidence suggests that leisure-time physical activity is associated with a reduced risk of endometrial cancer (EC), the shape of dose-response relationship has not been investigated and previous meta-analyses have not accounted for differences in measures of physical activity. To address such issues, we conducted linear and nonlinear dose-response meta-analyses by metabolic equivalent of task (MET)-hour/week and hour/week, respectively, based on observational studies published up to September 2013 identified from PubMed and Embase databases. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. In the linear dose-response analysis, an increase in leisure-time physical activity by 3 MET-hour/week was associated with an-2% reduced risk of EC (summary RR=0.98, p=0.02, 95% CI=0.95-1.00, I²=53%, p_{heterogeneity}=0.06, three case-control studies and three cohort studies, 3,460 cases, range of activity=0-50 MET-hour/week) and an increase by an hour/week was associated with an-5% reduced risk of EC (summary RR=0.95, p<0.001, 95% CI=0.93-0.98, I ²=31%, p_{heterogeneity}=0.20, four case-control studies and two cohort studies, 3,314 cases, range of activity=0-12 hour/week). Nonlinear dose-response meta-analysis suggested that the curve may plateau at 10 MET-hour/week (p_{change in slope}=0.04) but this statistical significance was sensitive to one study. No evidence of a nonlinear association was indicated by hour/week (p_{change in slope}>0.69). In conclusion, an increase in leisure-time physical activity may continue to decrease EC risk, within the range of 0-50 MET-hour/week or 0-15 hour/week. Future studies should evaluate possible independent role of intensity of physical activity and effect modification by obesity. What's new? Physical activity offers protection against endometrial cancer (EC), but it does so in a dose-response manner, with duration and type of activity possibly influencing the degree of EC risk reduction. In this meta-analysis of observational studies, the dose-response relationship between leisure-time physical activity and EC risk was found to be linear, with increasing physical activity (measured as metabolic equivalent of task [MET]-hours/week or hour/week) being linked to a continued decrease in EC risk. Non-linear meta-analysis suggested that benefits may plateau at 10 MET-hours/week, but the finding was driven by one study.