title: Visceral adiposity and colorectal adenomas: dose-response meta-analysis of observational studies.
abstract: BACKGROUND
  Obesity-related hormonal and metabolic perturbations 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 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.
  
  
  METHODS
  We conducted a dose-response meta-analysis to summarize the relationships between VAT and colorectal adenomas and to examine the value of VAT as an independent risk factor beyond BMI, WC, and SAT. PubMed and Embase were searched through September 2014 to identify relevant observational studies. The summary odds ratio (OR) 95% confidence interval (CI) were estimated using a random-effects model.
  
  
  RESULTS
  In linear dose-response meta-analysis, the summary OR for each 25 cm(2) increase in VAT area was 1.13 (95% CI 1.05-1.21; I(2) = 62%; 6 studies; 2776 cases; range of VAT area = 30-228 cm(2)). The dose-response curve suggested no evidence of nonlinearity (Pnon-linearity = 0.37). In meta-analysis comparing the highest versus 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 nonadvanced adenomas.
  
  
  CONCLUSIONS
  VAT may be the underlying mediator of the observed associations of BMI and WC with adenomas, increasing adenoma risk continuously 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 recommended to use both BMI and WC to identify those at high risk for colorectal neoplasia.
authors.affiliation: Department of Nutrition and Epidemiology. Electronic address: nak212@mail.harvard.edu.
authors.forename: N
authors.initials: N
authors.lastname: Keum
authors.affiliation: Department of Nutrition and Epidemiology.
authors.forename: D H
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kim
authors.affiliation: Division of Biostatistics, University of Leeds, Leeds, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Greenwood
authors.affiliation: Department of Nutrition and Epidemiology; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Giovannucci
mesh_terms: D000236:Adenoma / Q000453:epidemiology* / Q000473:pathology; D050154:Adiposity; D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D050152:Intra-Abdominal Fat / Q000503:physiopathology*; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D064887:Observational Studies as Topic; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D055105:Waist Circumference
keywords: colorectal adenomas; dose–response meta-analysis; observational studies; visceral adipose tissue; visceral adiposity