Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;9(1):e000817.
doi: 10.1136/bmjgast-2021-000817.

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

Alasdair Taylor  1 , Moneeza K Siddiqui  1 , Philip Ambery  2 , Javier Armisen  3 , Benjamin G Challis  4 , Carolina Haefliger  5 , Ewan R Pearson  1 , Alex S F Doney  1 , John F Dillon  6 , Colin N A Palmer  7
Affiliations

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

Alasdair Taylor et al. BMJ Open Gastroenterol. 2022 Mar.

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.

Keywords: cancer; epidemiology; fatty liver; genetics; obesity.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Philip Ambery, Javier Armisen, Benjamin Challis and Carolina Haefliger are employees of AstraZeneca and are shareholders of AstraZeneca.

Figures

Figure 1
Figure 1
Hazard Ratios for Cancer Incidence in GoDARTS and SHARE - GoDARTS, Genetics of Diabetes Audit and Research Tayside, Scotland; SHARE, Scottish Health Research Register.
Figure 2
Figure 2
Hazard Ratios for Cancer Incidence at Specific Sites in Meta-Analyis of GoDARTS and SHAREGoDARTS, Genetics of Diabetes Audit and Research Tayside, NAFLD, non-alcoholic fatty liver disease; Scotland; SHARE, Scottish Health Research Register.
Figure 3
Figure 3
Forest plot of Cancer Incidence and PNPLA3 rs738409 in GoDARTS, SHARE, and meta-analysis of both cohorts. GoDARTS, Genetics of Diabetes Audit and Research Tayside, Scotland; SHARE, Scottish Health Research Register.
See this image and copyright information in PMC

References

    1. Younossi Z, Loomba R, Rinella M. Current and future therapeutic regimens for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Hepatology 2017;5:1–36.
    1. Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatol 2013;10:656–65. 10.1038/nrgastro.2013.183 - DOI - PubMed
    1. Kim G-A, Lee HC, Choe J, et al. Association between non-alcoholic fatty liver disease and cancer incidence rate. J Hepatol 2018;68:140–6. 10.1016/j.jhep.2017.09.012 - DOI - PubMed
    1. Allen AM, Hicks SB, Mara KC, et al. The risk of incident extrahepatic cancers is higher in non-alcoholic fatty liver disease than obesity - A longitudinal cohort study. J Hepatol 2019;71:1229–36. 10.1016/j.jhep.2019.08.018 - DOI - PMC - PubMed
    1. Younossi ZM, Stepanova M, Negro F, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine 2012;91:319–27. 10.1097/MD.0b013e3182779d49 - DOI - PubMed

Publication types

MeSH terms