title: Adiposity and cancer at major anatomical sites: umbrella review of the literature.
abstract: ObjectiveTo evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer.DesignUmbrella review of systematic reviews and meta-analyses.Data sourcesPubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references.Eligibility criteriaSystematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer.Data synthesisPrimary analysis focused on cohort studies exploring associations for continuous measures of adiposity. 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, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings.Results204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m2increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality.ConclusionsAlthough the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.
authors.affiliation: Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London W12 0NN, UK m.kyrgiou@imperial.ac.uk.|West London Gynaecological Cancer Centre, Queen Charlotte's and Chelsea Hospital, Hammersmith Hospital, Imperial Healthcare NHS Trust, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Kyrgiou
authors.affiliation: Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kalliala
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Markozannes
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Department of Obstetrics and Gynaecology, University of Ioannina, Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Paraskevaidis
authors.affiliation: Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London W12 0NN, UK.|West London Gynaecological Cancer Centre, Queen Charlotte's and Chelsea Hospital, Hammersmith Hospital, Imperial Healthcare NHS Trust, London, UK.
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.affiliation: Department of Gynaecologic Oncology, Lancashire Teaching Hospitals, Preston, UK.|Department of Biophysics, University of Lancaster, Lancaster, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Martin-Hirsch
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.|Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London UK.
authors.forename: Konstantinos K
authors.initials: KK
authors.lastname: Tsilidis
mesh_terms: D050154:Adiposity; D006801:Humans; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000453:epidemiology* / Q000503:physiopathology*; D064887:Observational Studies as Topic