Adiposity and cancer at all anatomic sites: an umbrella review of the literature

Abstract

Objective: Although meta-analyses support associations between obesity and several cancers, some of the claimed associations may be flawed due to inherent biases. We evaluated strength and validity of the evidence for adiposity and risk of cancer development and mortality using an umbrella review methodology. Methods: Design: An umbrella review of systematic reviews and meta-analyses. Data sources: PubMed, EMBASE, Cochrane database of systematic reviews and manual screening. Eligibility criteria for selecting studies: Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer. Main Outcomes: Primary analysis focused on cohort studies exploring associations for continuous contrasts of adiposity. Data synthesis: The evidence was graded into strong, highly suggestive, suggestive or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings. Results: 204 meta-analyses investigated associations between seven indices of adiposity and the development or death from 36 primary cancers and their sub-types. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, 12 (13%) associations for nine cancers demonstrated strong evidence. Elevated BMI was associated with a higher risk of developing oesophageal adenocarcinoma, colon and rectal cancer in men, biliary tract, pancreatic, endometrial cancer in pre-menopausal women, kidney cancer and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with a higher risk of post-menopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. Conclusions: Although the association of adiposity with cancer risk has been extensively studied, associations for only nine cancers were graded with strong evidence. Other associations could be genuine, but there is still substantial uncertainty about them. In an era where obesity is becoming one of the greatest public health problems, evidence on the strength of the associated risks may allow finer selection of individuals at higher risk of cancer, who could be targeted for personalized prevention strategies.