title: Excess adiposity and gastrointestinal cancer.
abstract: BACKGROUND
  Excess adiposity is a risk factor for incidence of several gastrointestinal cancers, but it is unclear how these epidemiological observations translate into clinical practice.
  
  
  METHODS
  Critical appraisals and updated analyses of published systematic reviews were undertaken to quantify cancer risk associations better and to assess the impact of weight-reducing strategies (surgical and non-surgical) on cancer prevention.
  
  
  CONCLUSIONS
  A large volume of evidence demonstrates that body mass index (BMI), as an approximation for general adiposity, is a risk factor for the development of oesophageal adenocarcinoma, and colorectal, hepatocellular, gallbladder and pancreatic cancers. A smaller volume of evidence demonstrates that indices of increased central adiposity (such as waist circumference) are associated with increased risk of oesophageal adenocarcinoma and colorectal cancer, but these indices are not necessarily better predictors of risk compared with BMI. Several biological mechanisms may explain these associations but each hypothesis has several caveats and weaknesses. There are few data that convincingly demonstrate significant reductions in risk of gastrointestinal cancers following weight-reducing strategies. In turn, there are many methodological pitfalls in this literature, which prevent conclusive interpretation. The lack of robust intermediary obesity-related biomarkers is an additional unresolved challenge for prevention trials. Novel underpinning mechanisms (for example, local ectopic fat) and more accurate methods to measure these intermediaries are sought and explored as the most optimistic research strategies for the future.
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: P O
authors.initials: PO
authors.lastname: Coe
authors.forename: D A
authors.initials: DA
authors.lastname: O'Reilly
authors.forename: A G
authors.initials: AG
authors.lastname: Renehan
mesh_terms: D054392:Adipokines / Q000502:physiology; D050154:Adiposity / Q000502:physiology*; D050110:Bariatric Surgery; D002986:Clinical Trials as Topic; D004067:Digestive System Neoplasms / Q000209:etiology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007328:Insulin / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000502:physiology; D008297:Male; D009765:Obesity / Q000150:complications*; D011230:Precancerous Conditions / Q000209:etiology; D012307:Risk Factors; D015431:Weight Loss / Q000502:physiology
chemical_list: D054392:Adipokines; D012739:Gonadal Steroid Hormones; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins