Statin use and risk of liver cancer: Evidence from two population‐based studies

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self‐reported statin use and cancer‐registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case–control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43–0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24–0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45–2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.

[1]  J. Meyerhardt,et al.  Association Between Aspirin Use and Risk of Hepatocellular Carcinoma , 2018, JAMA oncology.

[2]  S. Asch,et al.  Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease. , 2018, Gastroenterology.

[3]  K. McGlynn,et al.  Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink , 2018, Gut.

[4]  S. Friis,et al.  Statin use and risk of contralateral breast cancer: a nationwide cohort study , 2018, British Journal of Cancer.

[5]  A. Hung,et al.  Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer , 2018, Cancer Causes & Control.

[6]  A. Thrift,et al.  Proton pump inhibitor and histamine‐2 receptor antagonist use and risk of liver cancer in two population‐based studies , 2018, Alimentary pharmacology & therapeutics.

[7]  Jiaquan Xu Trends in Liver Cancer Mortality Among Adults Aged 25 and Over in the United States, 2000-2016. , 2018, NCHS data brief.

[8]  Chia‐Fen Tsai,et al.  Statins decrease the risk of decompensation in hepatitis B virus– and hepatitis C virus–related cirrhosis: A population‐based study , 2017, Hepatology.

[9]  Xiang Cheng,et al.  Statins intake and risk of liver cancer , 2017, Medicine.

[10]  Miaoyin Liang,et al.  International incidence and mortality trends of liver cancer: a global profile , 2017, Scientific Reports.

[11]  H. El‐Serag,et al.  Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through 2012. , 2017, Gastroenterology.

[12]  Jesper Hallas,et al.  New use of prescription drugs prior to a cancer diagnosis , 2016, Pharmacoepidemiology and drug safety.

[13]  N. Moitt,et al.  Cancer incidence and mortality projections in the UK until 2035 , 2016, British Journal of Cancer.

[14]  G. Friedman,et al.  Statins and Reduced Risk of Liver Cancer: Evidence for Confounding. , 2016, Journal of the National Cancer Institute.

[15]  J. Gong,et al.  Meta-analysis of studies using statins as a reducer for primary liver cancer risk , 2016, Scientific Reports.

[16]  M. Zheng,et al.  Systematic review with network meta-analysis: statins and risk of hepatocellular carcinoma , 2016, Oncotarget.

[17]  A. Stiggelbout,et al.  Understanding Statin Non-Adherence: Knowing Which Perceptions and Experiences Matter to Different Patients , 2016, PloS one.

[18]  Yen-Chun Peng,et al.  Statins are associated with a reduced risk of cholangiocarcinoma: a population-based case-control study. , 2015, British journal of clinical pharmacology.

[19]  Jie Chen,et al.  Statin use and risk of primary liver cancer in the Clinical Practice Research Datalink. , 2015, Journal of the National Cancer Institute.

[20]  H. El‐Serag,et al.  Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population. , 2015, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[21]  Jiezhun Gu,et al.  Spectrum of statin hepatotoxicity: Experience of the drug‐induced liver injury network , 2014, Hepatology.

[22]  S. Taylor-Robinson,et al.  Incidence and mortality of primary liver cancer in England and Wales: changing patterns and ethnic variations. , 2014, World journal of gastroenterology.

[23]  C. la Vecchia,et al.  Statins and primary liver cancer: a meta-analysis of observational studies , 2013, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[24]  M. Murad,et al.  Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. , 2013, Gastroenterology.

[25]  Anders Engeland,et al.  Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults , 2012, International journal of cancer.

[26]  Zhi‐Jie Zheng,et al.  Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis. , 2012, The Journal of clinical endocrinology and metabolism.

[27]  J. Samet,et al.  Total cholesterol and cancer risk in a large prospective study in Korea. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  Patrick Royston,et al.  Multiple imputation using chained equations: Issues and guidance for practice , 2011, Statistics in medicine.

[29]  Jure Acimovic,et al.  Lovastatin prevents carcinogenesis in a rat model for liver cancer. Effects of ubiquinone supplementation. , 2010, Anticancer research.

[30]  M. Kenward,et al.  Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls , 2009, BMJ : British Medical Journal.

[31]  Stephen B. Gruber,et al.  Statins and cancer prevention , 2005, Nature Reviews Cancer.

[32]  C. Heeschen,et al.  Statins Have Biphasic Effects on Angiogenesis , 2002, Circulation.

[33]  G. Capurso,et al.  Statin use is associated to a reduced risk of pancreatic cancer: A meta-analysis. , 2019, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[34]  V. Debari,et al.  Role of Non-Selective Beta Blockers in Hepatocellular Carcinoma: An Analysis in Patients with Cirrhosis and Portal Hypertension , 2015 .

[35]  J. Samet,et al.  Food and Drug Administration , 2007, BMJ : British Medical Journal.