Epidemiological studies have indicated a positive association between adiposity and gallbladder disease risk, however, the shape of the dose-response relationship and differences between overall and abdominal adiposity remains to be clarified. We conducted a systematic review and dose-response meta-analysis of cohort studies of body mass index (BMI), waist circumference and waist-to-hip ratio and risk of gallbladder disease. PubMed and Embase databases were searched up to January 9th 2015. Summary relative risks were calculated using a random effects model. Seventeen prospective studies of BMI and gallbladder disease risk with 55,670 cases among 1,921,103 participants were included. The summary relative risk (RR) for a 5 unit increment in BMI was 1.63 (95 % CI 1.49-1.78, I(2) = 98 %). There was evidence of a nonlinear association overall and among women, p(nonlinearity) < 0.0001, but not among men, p(nonlinearity) = 0.99, with a slight flattening of the curve at very high BMI levels (BMI 40-45), however, the risk of gallbladder disease increased almost twofold even within the "normal" BMI range. The summary RR for a 10 cm increase in waist circumference was 1.46 (95 % CI 1.24-1.72, I(2) = 98 %, n = 5) and for a 0.1 unit increment in waist-to-hip ratio was 1.44 (95 % CI 1.26-1.64, I(2) = 92 %, n = 4). Associations were attenuated, but still significant, when BMI and abdominal adiposity measures were mutually adjusted. Our results confirm a positive association between both general and abdominal fatness and the risk of gallbladder disease. There is an almost twofold increase in the risk even within the "normal" BMI range, suggesting that even moderate increases in BMI may increase risk.
Keywords: Body mass index; Cohort studies; Gallbladder disease; Gallstones; Meta-analysis; Systematic review; Waist circumference; Waist-to-hip ratio.