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Associations Between Nonalcoholic Fatty Liver Disease and Cancers in a Large Cohort in China

  • Author Footnotes
    a Authors contributed equally to this work.
    Zhenyu Wang
    Footnotes
    a Authors contributed equally to this work.
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Author Footnotes
    a Authors contributed equally to this work.
    Xinyu Zhao
    Footnotes
    a Authors contributed equally to this work.
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Shuohua Chen
    Affiliations
    Cardiology Department, Kailuan General Hospital, Tangshan, China
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  • Yanhong Wang
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Liying Cao
    Affiliations
    Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, China
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  • Wei Liao
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Yuanyuan Sun
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Xiaomo Wang
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Yuan Zheng
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Shouling Wu
    Correspondence
    Shouling Wu, MD, Cardiology Department, Kailuan General Hospital, Tangshan 063000, China. fax: 0315-2820331.
    Affiliations
    Cardiology Department, Kailuan General Hospital, Tangshan, China
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  • Li Wang
    Correspondence
    Reprint requests Address requests for reprints to: Li Wang, PhD, Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China. fax: 8610-65233870.
    Affiliations
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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  • Author Footnotes
    a Authors contributed equally to this work.

      Background & Aims

      The relationship between nonalcoholic fatty liver disease (NAFLD) and cancer, especially extrahepatic cancers, has not been fully clarified. We analyzed data from a large prospective cohort study to determine the relationship between NAFLD and development of cancers in men.

      Methods

      We collected data from the Kailuan cohort, a community-based cohort of 54,187 adult men in China, from June 2006 through October 2007. NAFLD was diagnosed by ultrasonography after excluding other causes related to chronic liver disease. Fine and Gray competing risk regression model was used to evaluate associations between NAFLD (without cirrhosis) and cancers.

      Results

      The prevalence of NAFLD was 32.3%. NAFLD was associated with increased risk of all cancers (hazard ratio [HR], 1.22; 95% CI, 1.10–1.36; P = .0001), thyroid cancer (HR, 2.79; 95% CI, 1.25–6.21; P = .01), and lung cancer (HR, 1.23; 95% CI, 1.02–1.49; P = .03). The association between NAFLD and risk of thyroid cancer increased with level of alanine aminotransferase (ALT). In men with NAFLD, level of ALT 80 U/L or more was associated with hepatocellular carcinoma (HR, 8.08; 95% CI, 2.46–26.56; P = .0006). NAFLD increased risk of colorectal cancer (HR, 1.96; 95% CI, 1.17–3.27) and lung cancer (HR, 1.38; 95% CI, 1.03–1.84) only in smokers. An association between NAFLD and kidney cancer (HR, 1.57; 95% CI, 1.03–2.40) was only observed in men without diabetes.

      Conclusions

      A cohort study from China found that men with NAFLD have a higher risk of extrahepatic cancers, including thyroid and lung cancer. In men with NAFLD, higher levels of ALT were associated with higher risk of thyroid and hepatocellular cancer. NAFLD increased risk of colorectal and lung cancer only in smokers, and increased risk of kidney cancer in men without diabetes.

      Keywords

      Abbreviations used in this paper:

      ALT (alanine aminotransferase), BMI (body mass index), CI (confidence interval), HBsAg (hepatitis B surface antigen), HCC (hepatocellular carcinoma), HR (hazard ratio), NAFLD (nonalcoholic fatty liver disease)
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      References

        • Younossi Z.M.
        • Koenig A.B.
        • Abdelatif D.
        • et al.
        Global epidemiology of nonalcoholic fatty liver disease: meta-analytic assessment of prevalence, incidence, and outcomes.
        Hepatology. 2016; 64: 73-84
        • Li Z.
        • Xue J.
        • Chen P.
        • et al.
        Prevalence of nonalcoholic fatty liver disease in mainland of China: a meta-analysis of published studies.
        J Gastroenterol Hepatol. 2014; 29: 42-51
        • Kim G.-A.
        • Lee H.C.
        • Choe J.
        • et al.
        Association between non-alcoholic fatty liver disease and cancer incidence rate.
        J Hepatol. 2017; 68: 140-146
        • Adams L.A.
        • Lymp J.F.
        • Sauver J.S.
        • et al.
        The natural history of nonalcoholic fatty liver disease: a population-based cohort study.
        Gastroenterology. 2005; 129: 113-121
        • Derra A.
        • Bator M.
        • Menzyk T.
        • et al.
        Underrated enemy: from nonalcoholic fatty liver disease to cancers of the gastrointestinal tract.
        Clin Exp Hepatol. 2018; 4: 55-71
        • Armstrong M.J.
        • Adams L.A.
        • Canbay A.
        • et al.
        Extrahepatic complications of nonalcoholic fatty liver disease.
        Hepatology. 2014; 59: 1174-1197
        • Adams L.A.
        • Waters O.R.
        • Knuiman M.W.
        • et al.
        NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study.
        Am J Gastroenterol. 2009; 104: 861-867
        • Hazlehurst J.M.
        • Woods C.
        • Marjot T.
        • et al.
        Non-alcoholic fatty liver disease and diabetes.
        Metabolism. 2016; 65: 1096-1108
        • Giovanni M.
        • Roberto G.
        • Tabibian J.H.
        • et al.
        Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.
        PLoS Med. 2014; 11e1001680
        • Younossi Z.M.
        • Otgonsuren M.
        • Henry L.
        • et al.
        Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009.
        Hepatology. 2015; 62: 1723-1730
        • Ahn J.S.
        • Sinn D.H.
        • Min Y.W.
        • et al.
        Non-alcoholic fatty liver diseases and risk of colorectal neoplasia.
        Aliment Pharmacol Ther. 2017; 45: 345-353
        • Wong V.W.
        • Wong G.L.
        • Tsang S.W.
        • et al.
        High prevalence of colorectal neoplasm in patients with non-alcoholic steatohepatitis.
        Gut. 2011; 60: 829-836
        • Kwak M.S.
        • Yim J.Y.
        • Yi A.
        • et al.
        Nonalcoholic fatty liver disease is associated with breast cancer in nonobese women.
        Dig Liver Dis. 2019; 51: 1030-1035
        • Chang C.F.
        • Tseng Y.C.
        • Huang H.H.
        • et al.
        Exploring the relationship between nonalcoholic fatty liver disease and pancreatic cancer by computed tomographic survey.
        Intern Emerg Med. 2018; 13: 191-197
        • Sanna C.
        • Rosso C.
        • Marietti M.
        • et al.
        Non-alcoholic fatty liver disease and extra-hepatic cancers.
        Int J Mol Sci. 2016; 17: 717
        • Wu S.
        • Huang Z.
        • Yang X.
        • et al.
        Prevalence of ideal cardiovascular health and its relationship with the 4-year cardiovascular events in a northern Chinese industrial city.
        Circ Cardiovasc Qual Outcomes. 2012; 5: 487-493
        • Gao X.
        • Fan J.G.
        • Study Group of L.
        • et al.
        Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology.
        J Diabetes. 2013; 5: 406-415
        • Shen X.
        • Jin C.
        • Wu Y.
        • et al.
        Prospective study of perceived dietary salt intake and the risk of non-alcoholic fatty liver disease.
        J Hum Nutr Diet. 2019; 32: 802-809
        • Group of China Obesity Task Force
        Guidelines for the prevention and control of overweight and obesity in Chinese adults (excerpt).
        Acta Nutrimenta Sinica. 2004; 26: 1-4
        • Chobanian A.V.
        • Bakris G.L.
        • Black H.R.
        The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. The JNC 7 report.
        JAMA. 2003; 289: 2560-2572
        • Fine J.P.
        • Gray R.J.
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Stat Assoc. 1999; 94: 496-509
        • Wade K.H.
        • Carslake D.
        • Sattar N.
        • et al.
        BMI and mortality in UK Biobank: revised estimates using mendelian randomization.
        Obesity (Silver Spring). 2018; 26: 1796-1806
        • Bhaskaran K.
        • Dos-Santos-Silva I.
        • Leon D.A.
        • et al.
        Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK.
        Lancet Diabetes Endocrinol. 2018; 6: 944-953
        • Kjøllesdal M.K.R.
        • Smith G.D.
        • Ariansen I.
        • et al.
        The association between BMI and mortality using early adulthood BMI as an instrumental variable for midlife BMI.
        Sci Rep. 2018; 8: 11499
      1. Global BMIMC, Di Angelantonio E, Bhupathiraju Sh N, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 2016;388:776–786.

        • Desquilbet L.
        • Mariotti F.
        Dose-response analyses using restricted cubic spline functions in public health research.
        Stat Med. 2010; 29: 1037-1057
        • Kim W.R.
        • Flamm S.L.
        • Di Bisceglie A.M.
        • et al.
        Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease.
        Hepatology. 2008; 47: 1363-1370
        • Sung K.C.
        • Lee M.Y.
        • Lee J.Y.
        • et al.
        Utility of ALT concentration in men and women with nonalcoholic fatty liver disease: cohort study.
        J Clin Med. 2019; 8: 445
        • Kwak M.S.
        • Kim E.
        • Jang E.J.
        • et al.
        The association of non-alcoholic fatty liver disease with lung function: a survey design analysis using propensity score.
        Respirology. 2018; 23: 82-88
        • Mantovani A.
        • Lonardo A.
        • Vinco G.
        • et al.
        Association between non-alcoholic fatty liver disease and decreased lung function in adults: a systematic review and meta-analysis.
        Diabetes Metab. 2019; 45: 536-544
        • Vernon G.
        • Baranova A.
        • Younossi Z.M.
        Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults.
        Aliment Pharmacol Ther. 2011; 34: 274-285
        • Lonardo A.
        • Bellentani S.
        • Argo C.K.
        • et al.
        Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups.
        Dig Liver Dis. 2015; 47: 997-1006
        • Schmid D.
        • Ricci C.
        • Behrens G.
        • et al.
        Adiposity and risk of thyroid cancer: a systematic review and meta-analysis.
        Obes Rev. 2015; 16: 1042-1054
        • Kitahara C.M.
        • McCullough M.L.
        • Franceschi S.
        • et al.
        Anthropometric factors and thyroid cancer risk by histological subtype: pooled analysis of 22 prospective studies.
        Thyroid. 2016; 26: 306-318
        • Gursoy A.
        Rising thyroid cancer incidence in the world might be related to insulin resistance.
        Med Hypotheses. 2010; 74: 35-36
        • Hidayat K.
        • Du X.
        • Chen G.
        • et al.
        Abdominal obesity and lung cancer risk: systematic review and meta-analysis of prospective studies.
        Nutrients. 2016; 8: 810
        • Argirion I.
        • Weinstein S.J.
        • Mannisto S.
        • et al.
        Serum insulin, glucose, indices of insulin resistance, and risk of lung cancer.
        Cancer Epidemiol Biomarkers Prev. 2017; 26: 1519-1524
        • Petridou E.T.
        • Sergentanis T.N.
        • Antonopoulos C.N.
        • et al.
        Insulin resistance: an independent risk factor for lung cancer?.
        Metabolism. 2011; 60: 1100-1106
        • Liu Y.
        • Wang W.
        • Yu X.
        • et al.
        Thyroid function and risk of non-alcoholic fatty liver disease in euthyroid subjects.
        Ann Hepatol. 2018; 17: 779-788
        • Haymart M.R.
        • Glinberg S.L.
        • Liu J.
        • et al.
        Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension.
        Clin Endocrinol (Oxf). 2009; 71: 434-439
        • Adams L.A.
        • Anstee Q.M.
        • Tilg H.
        • et al.
        Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases.
        Gut. 2017; 66: 1138-1153
        • Hwang S.T.
        • Cho Y.K.
        • Park J.H.
        • et al.
        Relationship of non-alcoholic fatty liver disease to colorectal adenomatous polyps.
        J Gastroenterol Hepatol. 2010; 25: 562-567
        • Lin X.F.
        • Shi K.Q.
        • You J.
        • et al.
        Increased risk of colorectal malignant neoplasm in patients with nonalcoholic fatty liver disease: a large study.
        Mol Biol Rep. 2014; 41: 2989-2997
        • Stadlmayr A.
        • Aigner E.
        • Steger B.
        • et al.
        Nonalcoholic fatty liver disease: an independent risk factor for colorectal neoplasia.
        J Intern Med. 2011; 270: 41-49
        • Huang K.W.
        • Leu H.B.
        • Wang Y.J.
        • et al.
        Patients with nonalcoholic fatty liver disease have higher risk of colorectal adenoma after negative baseline colonoscopy.
        Colorectal Dis. 2013; 15: 830-835
        • Lee Y.I.
        • Lim Y.S.
        • Park H.S.
        Colorectal neoplasms in relation to non-alcoholic fatty liver disease in Korean women: a retrospective cohort study.
        J Gastroenterol Hepatol. 2012; 27: 91-95
        • Sørensen H.T.
        • Mellemkjaer L.
        • Jepsen P.
        • et al.
        Risk of cancer in patients hospitalized with fatty liver: a Danish cohort study.
        J Clin Gastroenterol. 2003; 36: 356-359
        • Siddharth S.
        • Sharma A.N.
        • Mohammad Hassan M.
        • et al.
        Central adiposity is associated with increased risk of esophageal inflammation, metaplasia, and adenocarcinoma: a systematic review and meta-analysis.
        Clin Gastroenterol Hepatol. 2013; 11: 1399
        • Tilg H.
        • Moschen A.R.
        • Roden M.
        NAFLD and diabetes mellitus.
        Nat Rev Gastroenterol Hepatol. 2017; 14: 32-42
        • Choi Y.J.
        • Lee D.H.
        • Han K.D.
        • et al.
        Is nonalcoholic fatty liver disease associated with the development of prostate cancer? A nationwide study with 10,516,985 Korean men.
        PLoS One. 2018; 13e0201308
        • Golabek T.
        • Bukowczan J.
        • Chlosta P.
        • et al.
        Obesity and prostate cancer incidence and mortality: a systematic review of prospective cohort studies.
        Urol Int. 2014; 92: 7-14
        • Dasarathy S.
        • Dasarathy J.
        • Khiyami A.
        • et al.
        Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study.
        J Hepatol. 2009; 51: 1061-1067
        • de Martel C.
        • Maucort-Boulch D.
        • Plummer M.
        • et al.
        World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma.
        Hepatology. 2015; 62: 1190-1200