title: Metabolic risk factors for esophageal squamous cell carcinoma and adenocarcinoma: a prospective study of 580,000 subjects within the Me-Can project.
abstract: BACKGROUND
  Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study.
  
  
  METHODS
  The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox's proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS).
  
  
  RESULTS
  In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC.
  
  
  CONCLUSIONS
  In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the metabolic state of the MetS, considering that no other metabolic factor than BMI was associated with EAC.
authors.affiliation: Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. bjorn.lindkvist@vgregion.se.
authors.forename: Björn
authors.initials: B
authors.lastname: Lindkvist
authors.forename: Dorthe
authors.initials: D
authors.lastname: Johansen
authors.forename: Tanja
authors.initials: T
authors.lastname: Stocks
authors.forename: Hans
authors.initials: H
authors.lastname: Concin
authors.forename: Tone
authors.initials: T
authors.lastname: Bjørge
authors.forename: Martin
authors.initials: M
authors.lastname: Almquist
authors.forename: Christel
authors.initials: C
authors.lastname: Häggström
authors.forename: Anders
authors.initials: A
authors.lastname: Engeland
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Gabriele
authors.initials: G
authors.lastname: Nagel
authors.forename: Håkan
authors.initials: H
authors.lastname: Jonsson
authors.forename: Randi
authors.initials: R
authors.lastname: Selmer
authors.forename: Hanno
authors.initials: H
authors.lastname: Ulmer
authors.forename: Steinar
authors.initials: S
authors.lastname: Tretli
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D000328:Adult; D001317:Austria / Q000453:epidemiology; D001786:Blood Glucose / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D001786:Blood Glucose