Visceral adiposity and colorectal adenomas: Dose-response meta-analysis of observational studies

Importance: Obesity-related hormonal and metabolic alterations implicated in colorectal carcinogenesis are mainly driven by visceral adipose tissue (VAT) rather than subcutaneous adipose tissue (SAT). Yet, most epidemiologic studies have examined the relationship between excess adiposity and colorectal neoplasia using a surrogate marker of VAT such as body mass index (BMI) and waist circumference (WC). Due to the inability of BMI and WC to distinguish VAT from SAT, they are likely to have underestimated the true association. Objective: We conducted a dose-response meta-analysis to summarize the relationships between visceral adiposity and colorectal adenomas and to examine the value of VAT as an independent predictor beyond BMI, WC, SAT. Data Sources: PubMed and Embase were searched through September, 2014. Study Selection: Observational studies investigating the relationship between VAT as measured by CT or MRI and adenomas were included. Data Extraction and Synthesis: Data were extracted independently by two authors and inconsistency was checked by a third author. Summary odds ratio (OR) was estimated using a random-effects model. Main Outcomes and Measures: Colorectal adenomas. Results: In linear dose-response meta-analysis, the summary odds ratio (OR) for each 25 cm2 increase in VAT area was 1.13 (95% CI=1.05-1.21; I2=62%; 6 studies; 2,776 cases; range of VAT area=30-228 cm2). The dose-response curve suggested no evidence of non-linearity (Pnon-linearity=0.37). In meta-analysis comparing the highest vs. lowest category of VAT based on 12 studies, a positive association between VAT and adenomas remained statistically significant even after adjustment for BMI, WC, and SAT. In contrast, adjustment for VAT substantially attenuated associations of BMI, WC, and SAT with adenomas. Across the studies, VAT was more strongly associated with advanced adenomas than non-advanced adenomas. Conclusions and relevance: VAT may be the underlying mediator of the observed associations of BMI and WC with adenomas, continuing to increase adenoma risk over a wide range of VAT area. Considering that the joint use of BMI and WC better captures VAT than the use of either one, clinicians are recommend to use both BMI and WC to identify those at high risk for colorectal neoplasia.