Excess Body Mass Index and Risk of Liver Cancer: A Nonlinear Dose-Response Meta-Analysis of Prospective Studies

Background: Excess body weight measured as body mass index (BMI) has a positive association with risk of common cancers. However, previous meta-analyses related to BMI and liver cancer had inconsistent results. The purpose of the current study is to establish a nonlinear dose-response relationship between BMI and incidence risk of liver cancer. Methods: A systematic literature search for relevant articles published from 1966 to November 2011 was conducted in PUBMED and EMBASE digital databases. Additional articles were manually searched by using the reference lists of identified papers. Restricted cubic splines and generalized least-squares regression methods were used to model a potential curvilinear relationship and to make a dose-response meta-analysis. Stratified analysis, sensitivity analysis and assessment of bias were performed in our meta-analysis. Results: 8 articles including 1,779,471 cohort individuals were brought into meta-analysis. A non-linear dose-response association between BMI and risk of liver cancer was visually significant (P for nonlinearity<0.001), besides, the point value of BMI also enhanced the results quantitatively, where relative risks were 1.02 (95% CI = 1.02-1.03), 1.35 (95% CI = 1.24-1.47) and 2.22-fold (95% CI = 1.74-2.83) when BMI was at the point of 25, 30 and 35 kg/m(2) compared with reference (the median value of the lowest category), respectively. The ethnicity of the population was found as the main source of heterogeneity. In subsequent stratified analysis, no evidence of heterogeneity was showed in Asian and White populations (P for heterogeneity>0.1), and all value of BMI still presented significantly increased risk of cancer. Conclusions: The findings from meta-analysis provided that excess BMI had significant increased association with risk of liver cancer, although the biological mechanisms underlying the obesity-cancer link still need to be clarified.