PMID- 35338048
OWN - NLM
STAT- MEDLINE
DCOM- 20220414
LR  - 20220722
IS  - 2054-4774 (Print)
IS  - 2054-4774 (Electronic)
IS  - 2054-4774 (Linking)
VI  - 9
IP  - 1
DP  - 2022 Mar
TI  - Metabolic dysfunction-related liver disease as a risk factor for cancer.
LID - 10.1136/bmjgast-2021-000817 [doi]
LID - e000817
AB  - OBJECTIVE: The aim of this study was to investigate the association between 
      obesity, diabetes and metabolic related liver dysfunction and the incidence of 
      cancer. DESIGN: This study was conducted with health record data available from 
      the National Health Service in Tayside and Fife. Genetics of Diabetes Audit and 
      Research Tayside, Scotland (GoDARTS), Scottish Health Research Register (SHARE) 
      and Tayside and Fife diabetics, three Scottish cohorts of 13 695, 62 438 and 
      16 312 patients, respectively, were analysed in this study. Participants in 
      GoDARTS were a volunteer sample, with half having type 2 diabetes mellitus(T2DM). 
      SHARE was a volunteer sample. Tayside and Fife diabetics was a population-level 
      cohort. Metabolic dysfunction-related liver disease (MDLD) was defined using 
      alanine transaminase measurements, and individuals with alternative causes of 
      liver disease (alcohol abuse, viruses, etc) were excluded from the analysis. 
      RESULTS: MDLD associated with increased cancer incidence with a HR of 1.31 in a 
      Cox proportional hazards model adjusted for sex, type 2 diabetes, body mass 
      index(BMI), and smoking status (95% CI 1.27 to 1.35, p<0.0001). This was 
      replicated in two further cohorts, and similar associations with cancer incidence 
      were found for Fatty Liver Index (FLI), Fibrosis-4 Index (FIB-4) and 
      non-alcoholic steatohepatitis (NASH). Homozygous carriers of the common 
      non-alcoholic fatty liver disease (NAFLD) risk-variant PNPLA3 rs738409 had 
      increased risk of cancer. (HR=1.27 (1.02 to 1.58), p=3.1x10 (-)(2)). BMI was not 
      independently associated with cancer incidence when MDLD was included as a 
      covariate. CONCLUSION: MDLD, FLI, FIB-4 and NASH associated with increased risk 
      of cancer incidence and death. NAFLD may be a major component of the relationship 
      between obesity and cancer incidence.
CI  - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Taylor, Alasdair
AU  - Taylor A
AUID- ORCID: 0000-0002-4078-217X
AD  - Population Health and Genomics, University of Dundee, Dundee, UK.
FAU - Siddiqui, Moneeza K
AU  - Siddiqui MK
AD  - Population Health and Genomics, University of Dundee, Dundee, UK.
FAU - Ambery, Philip
AU  - Ambery P
AD  - Late Stage Development, Cardiovascular, Renal and Metabolism (CVRM), 
      BioPharmaceuticals R&D, AstraZeneca PLC, Gothenburg, Sweden.
FAU - Armisen, Javier
AU  - Armisen J
AD  - Early Clinical Development, Research and Early Development, Cardiovascular, Renal 
      and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca PLC, Cambridge, UK.
FAU - Challis, Benjamin G
AU  - Challis BG
AD  - Translational Science & Experimental Medicine, Research and Early Development, 
      Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, 
      Cambridge, UK.
FAU - Haefliger, Carolina
AU  - Haefliger C
AD  - Centre for Genomics Research, Discovery Sciences, Biopharmaceuticals R&D, 
      AstraZeneca, Cambridge, UK.
FAU - Pearson, Ewan R
AU  - Pearson ER
AD  - Population Health and Genomics, University of Dundee, Dundee, UK.
FAU - Doney, Alex S F
AU  - Doney ASF
AD  - Population Health and Genomics, University of Dundee, Dundee, UK.
FAU - Dillon, John F
AU  - Dillon JF
AD  - Molecular and Clinical Medicine, University of Dundee, Dundee, UK, University of 
      Dundee, Dundee, UK.
FAU - Palmer, Colin N A
AU  - Palmer CNA
AD  - Population Health and Genomics, University of Dundee, Dundee, UK 
      c.n.a.palmer@dundee.ac.uk.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - BMJ Open Gastroenterol
JT  - BMJ open gastroenterology
JID - 101660690
SB  - IM
MH  - *Diabetes Mellitus, Type 2/complications/epidemiology
MH  - Humans
MH  - *Metabolic Diseases/complications
MH  - *Neoplasms/complications/etiology
MH  - *Non-alcoholic Fatty Liver Disease/complications/epidemiology
MH  - Obesity/complications/epidemiology
MH  - Risk Factors
MH  - State Medicine
PMC - PMC8961105
OTO - NOTNLM
OT  - cancer
OT  - epidemiology
OT  - fatty liver
OT  - genetics
OT  - obesity
COIS- Competing interests: Philip Ambery, Javier Armisen, Benjamin Challis and Carolina 
      Haefliger are employees of AstraZeneca and are shareholders of AstraZeneca.
EDAT- 2022/03/27 06:00
MHDA- 2022/04/15 06:00
PMCR- 2022/03/25
CRDT- 2022/03/26 05:29
PHST- 2021/10/25 00:00 [received]
PHST- 2022/01/25 00:00 [accepted]
PHST- 2022/03/26 05:29 [entrez]
PHST- 2022/03/27 06:00 [pubmed]
PHST- 2022/04/15 06:00 [medline]
PHST- 2022/03/25 00:00 [pmc-release]
AID - bmjgast-2021-000817 [pii]
AID - 10.1136/bmjgast-2021-000817 [doi]
PST - ppublish
SO  - BMJ Open Gastroenterol. 2022 Mar;9(1):e000817. doi: 10.1136/bmjgast-2021-000817.