Metabolic dysfunction-related liver disease as a risk factor for cancer

Alasdair Taylor; Moneeza K. Siddiqui; Philip Ambery; Javier Armisen; Benjamin G. Challis; Carolina Haefliger; Ewan R. Pearson; Alex S. F. Doney; John F. Dillon; Colin N. A. Palmer

doi:10.1136/bmjgast-2021-000817

Metabolic dysfunction-related liver disease as a risk factor for cancer

Alasdair Taylor, Moneeza K. Siddiqui, Philip Ambery, Javier Armisen, Benjamin G. Challis, Carolina Haefliger, Ewan R. Pearson, Alex S. F. Doney, John F. Dillon, Colin N. A. Palmer (Lead / Corresponding author)

Population Health and Genomics

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Abstract

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=3.1×10 - 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.

Original language	English
Article number	e000817
Number of pages	10
Journal	BMJ Open Gastroenterology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1136/bmjgast-2021-000817
Publication status	Published - 25 Mar 2022

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10.1136/bmjgast-2021-000817Licence: CC BY-NC

Final Published VersionFinal published version, 1.11 MBLicence: CC BY-NC

The Tayside Bioresource: Leveraging Electronic Medical Records to Deliver Personalised Medicine (Biomedical Resource Grant)
Colhoun, H. (Investigator), Connell, J. (Investigator), Doney, A. (Investigator), Dow, E. (Investigator), Morris, A. (Investigator), Palmer, C. (Investigator), Pearson, E. (Investigator), Sullivan, F. (Investigator) & Treweek, S. (Investigator)
1/02/13 → 31/10/15
Project: Research

Health Informatics Centre
Health and Clinical Services
Facility/equipment: Facility

Cite this

@article{fca1625e10c34b9c8ccc64b8403e0c0d,

title = "Metabolic dysfunction-related liver disease as a risk factor for cancer",

abstract = "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=3.1×10 - 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.",

author = "Alasdair Taylor and Siddiqui, {Moneeza K.} and Philip Ambery and Javier Armisen and Challis, {Benjamin G.} and Carolina Haefliger and Pearson, {Ewan R.} and Doney, {Alex S. F.} and Dillon, {John F.} and Palmer, {Colin N. A.}",

note = "Funding Information: SHARE has ongoing funding from NHS Research Scotland and established by funding from The Wellcome Trust Biomedical Resource Grant Number 099177/Z/12/Z. The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS) was funded by The Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT program. {\textcopyright} 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.",

year = "2022",

month = mar,

day = "25",

doi = "10.1136/bmjgast-2021-000817",

language = "English",

volume = "9",

journal = "BMJ Open Gastroenterology",

issn = "2054-4774",

publisher = "BMJ Publishing Group",

number = "1",

}

TY - JOUR

T1 - Metabolic dysfunction-related liver disease as a risk factor for cancer

AU - Taylor, Alasdair

AU - Siddiqui, Moneeza K.

AU - Ambery, Philip

AU - Armisen, Javier

AU - Challis, Benjamin G.

AU - Haefliger, Carolina

AU - Pearson, Ewan R.

AU - Doney, Alex S. F.

AU - Dillon, John F.

AU - Palmer, Colin N. A.

N1 - Funding Information: SHARE has ongoing funding from NHS Research Scotland and established by funding from The Wellcome Trust Biomedical Resource Grant Number 099177/Z/12/Z. The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS) was funded by The Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT program. © 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.

PY - 2022/3/25

Y1 - 2022/3/25

N2 - 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=3.1×10 - 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.

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=3.1×10 - 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.

U2 - 10.1136/bmjgast-2021-000817

DO - 10.1136/bmjgast-2021-000817

M3 - Article

C2 - 35338048

SN - 2054-4774

VL - 9

JO - BMJ Open Gastroenterology

JF - BMJ Open Gastroenterology

IS - 1

M1 - e000817

ER -

Metabolic dysfunction-related liver disease as a risk factor for cancer

Abstract

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The Tayside Bioresource: Leveraging Electronic Medical Records to Deliver Personalised Medicine (Biomedical Resource Grant)

Equipment

Health Informatics Centre

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