title: Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort.
abstract: BACKGROUND
  Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce.
  
  
  METHODS
  We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals.
  
  
  RESULTS
  During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals.
  
  
  CONCLUSIONS
  This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.
authors.affiliation: Institute of Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany. schlesinger@epi.uni-kiel.de
authors.forename: S
authors.initials: S
authors.lastname: Schlesinger
authors.forename: K
authors.initials: K
authors.lastname: Aleksandrova
authors.forename: T
authors.initials: T
authors.lastname: Pischon
authors.forename: M
authors.initials: M
authors.lastname: Jenab
authors.forename: V
authors.initials: V
authors.lastname: Fedirko
authors.forename: E
authors.initials: E
authors.lastname: Trepo
authors.forename: K
authors.initials: K
authors.lastname: Overvad
authors.forename: N
authors.initials: N
authors.lastname: Roswall
authors.forename: A
authors.initials: A
authors.lastname: Tjønneland
authors.forename: M C
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: G
authors.initials: G
authors.lastname: Fagherazzi
authors.forename: A
authors.initials: A
authors.lastname: Racine
authors.forename: R
authors.initials: R
authors.lastname: Kaaks
authors.forename: V A
authors.initials: VA
authors.lastname: Grote
authors.forename: H
authors.initials: H
authors.lastname: Boeing
authors.forename: A
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: M
authors.initials: M
authors.lastname: Pantzalis
authors.forename: M
authors.initials: M
authors.lastname: Kritikou
authors.forename: A
authors.initials: A
authors.lastname: Mattiello
authors.forename: S
authors.initials: S
authors.lastname: Sieri
authors.forename: C
authors.initials: C
authors.lastname: Sacerdote
authors.forename: D
authors.initials: D
authors.lastname: Palli
authors.forename: R
authors.initials: R
authors.lastname: Tumino
authors.forename: P H
authors.initials: PH
authors.lastname: Peeters
authors.forename: H B
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: E
authors.initials: E
authors.lastname: Weiderpass
authors.forename: J R
authors.initials: JR
authors.lastname: Quirós
authors.forename: R
authors.initials: R
authors.lastname: Zamora-Ros
authors.forename: M J
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: L
authors.initials: L
authors.lastname: Arriola
authors.forename: E
authors.initials: E
authors.lastname: Ardanaz
authors.forename: M J
authors.initials: MJ
authors.lastname: Tormo
authors.forename: P
authors.initials: P
authors.lastname: Nilsson
authors.forename: B
authors.initials: B
authors.lastname: Lindkvist
authors.forename: M
authors.initials: M
authors.lastname: Sund
authors.forename: O
authors.initials: O
authors.lastname: Rolandsson
authors.forename: K T
authors.initials: KT
authors.lastname: Khaw
authors.forename: N
authors.initials: N
authors.lastname: Wareham
authors.forename: R C
authors.initials: RC
authors.lastname: Travis
authors.forename: E
authors.initials: E
authors.lastname: Riboli
authors.forename: U
authors.initials: U
authors.lastname: Nöthlings
mesh_terms: D001661:Biliary Tract Neoplasms / Q000150:complications / Q000453:epidemiology*; D001823:Body Composition; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005060:Europe; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000150:complications / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D057566:Self Report
chemical_list: D007328:Insulin
keywords: biliary tract neoplasms; diabetes duration; diabetes mellitus; gallbladder neoplasms; hepatocellular carcinoma; insulin treatment