Metabolic dysfunction-related liver disease as a risk factor for cancer
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 Diabete...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-11-01
|
| Series: | BMJ Open Gastroenterology |
| Online Access: | https://bmjopengastro.bmj.com/content/9/1/e000817.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849692732121939968 |
|---|---|
| author | John F Dillon Ewan R Pearson Colin N A Palmer Alasdair Taylor Moneeza K Siddiqui Philip Ambery Javier Armisen Benjamin G Challis Carolina Haefliger Alex S F Doney |
| author_facet | John F Dillon Ewan R Pearson Colin N A Palmer Alasdair Taylor Moneeza K Siddiqui Philip Ambery Javier Armisen Benjamin G Challis Carolina Haefliger Alex S F Doney |
| author_sort | John F Dillon |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7e53cb4a438d4433baaddbc4e6123d19 |
| institution | DOAJ |
| issn | 2054-4774 |
| language | English |
| publishDate | 2022-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Gastroenterology |
| spelling | doaj-art-7e53cb4a438d4433baaddbc4e6123d192025-08-20T03:20:37ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742022-11-019110.1136/bmjgast-2021-000817Metabolic dysfunction-related liver disease as a risk factor for cancerJohn F Dillon0Ewan R Pearson1Colin N A Palmer2Alasdair Taylor3Moneeza K Siddiqui4Philip Ambery5Javier Armisen6Benjamin G Challis7Carolina Haefliger8Alex S F Doney94 Ninewells Hospital and Medical School, Dundee, UKPopulation Health and Genomics, University of Dundee, Dundee, UKDivision of Population Health and Genomics, University of Dundee, Dundee, UKDepartment of Anaesthesia, NHS Tayside, Dundee, UKprincipal investigator (tenure track)Clinical Late Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, SwedenEarly Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca PLC, Cambridge, UKTranslational Science & Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UKCentre for Genomics Research, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UKPopulation Health and Genomics, University of Dundee, Dundee, UKObjective 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.https://bmjopengastro.bmj.com/content/9/1/e000817.full |
| spellingShingle | John F Dillon Ewan R Pearson Colin N A Palmer Alasdair Taylor Moneeza K Siddiqui Philip Ambery Javier Armisen Benjamin G Challis Carolina Haefliger Alex S F Doney Metabolic dysfunction-related liver disease as a risk factor for cancer BMJ Open Gastroenterology |
| title | Metabolic dysfunction-related liver disease as a risk factor for cancer |
| title_full | Metabolic dysfunction-related liver disease as a risk factor for cancer |
| title_fullStr | Metabolic dysfunction-related liver disease as a risk factor for cancer |
| title_full_unstemmed | Metabolic dysfunction-related liver disease as a risk factor for cancer |
| title_short | Metabolic dysfunction-related liver disease as a risk factor for cancer |
| title_sort | metabolic dysfunction related liver disease as a risk factor for cancer |
| url | https://bmjopengastro.bmj.com/content/9/1/e000817.full |
| work_keys_str_mv | AT johnfdillon metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT ewanrpearson metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT colinnapalmer metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT alasdairtaylor metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT moneezaksiddiqui metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT philipambery metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT javierarmisen metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT benjamingchallis metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT carolinahaefliger metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer AT alexsfdoney metabolicdysfunctionrelatedliverdiseaseasariskfactorforcancer |