Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies

De-Sen Xiang; Jing Zhang

doi:doi:10.11648/j.sjph.20160402.11

| Peer-Reviewed

Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies

De-Sen Xiang, Jing Zhang

Published in Science Journal of Public Health (Volume 4, Issue 2)

Received: 3 February 2016 Accepted: 17 February 2016 Published: 1 March 2016

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

The relationship between statin use and the risk of hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to clarify this issue. Data on the relationship between statin use and the risk of HCC were collected through an electronic search of PubMed database. Summary odds ratios (ORs) with 95% confidential intervals were calculated using a random-effects model. Six studies were selected for the final meta-analysis, involving 3778 cases and 482452 patients. Our meta-analysis showed that statin use was significantly associated with a decreased risk of HCC (OR, 0.60, 95% confidence interval, 0.48–0.76). In conclusion, the meta-analysis suggests that statin use is associated with a reduced risk of HCC. However, our findings should be interpreted with caution due to limited studies.

Published in	Science Journal of Public Health (Volume 4, Issue 2)
DOI	10.11648/j.sjph.20160402.11
Page(s)	81-87
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2016. Published by Science Publishing Group

Keywords

Statin, Hepatocellular Carcinoma, Meta-Analysis

References

[1]	Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008 GLOBOCAN 2008. International journal of cancer Journal international du cancer 2010; 127(12): 2893-917.
[2]	Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary pharmacology & therapeutics 2011; 34(3): 274-85.
[3]	Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366(9493): 1267-78.
[4]	Maheshwari RA, Balaraman R, Sailor GU, et al. Protective effect of simvastatinand rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats. Indian journal of pharmacology 2015; 47(1): 17-21.
[5]	Olivan M, Rigau M, Colas E, et al. Simultaneous treatment with statins and aspirin reduces the risk of prostate cancer detection and tumorigenic properties in prostate cancer cell lines. BioMed research international 2015; 2015: 762178.
[6]	Chen Y, Zhang S, Peng G, et al. Endothelial NO synthase and reactive oxygen species mediated effect of simvastatin on vessel structure and function: pleiotropic and dose-dependent effect on tumor vascular stabilization. International journal of oncology 2013; 42(4): 1325-36.
[7]	Demierre MF, Higgins PD, Gruber SB, et al. Statins and cancer prevention. Nature reviews Cancer 2005; 5(12): 930-42.
[8]	Sun HY, Singh N. Antimicrobial and immunomodulatory attributes of statins: relevance in solid-organ transplant recipients. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2009; 48(6): 745-55.
[9]	Shi M, Zheng H, Nie B, et al. Statin use and risk of liver cancer: an update meta-analysis. BMJ open 2014; 4(9): e005399.
[10]	Singh, S., Singh, P. P., Singh, A. G., et al. Statins are associated with a reduced risk of hepatocellular cancer: A systematic review and meta-analysis. Gastroenterology. 144, 323-332 (2013).
[11]	Pradelli, D. Soranna D, Scotti L, et al. Statins and primary liver cancer: a meta-analysis of observational studies. European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP). 22, 229-234, doi: 10.1097/CEJ.0b013e328358761a (2013).
[12]	Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert opinion on drug safety 2010; 9(4): 603-21.
[13]	McGlynn KA, Divine GW, Sahasrabuddhe VV, et al. Statin use and risk of hepatocellular carcinoma in a U. S. population. Cancer epidemiology 2014; 38(5): 523-7.
[14]	Bjorkhem-Bergman L, Backheden M, Soderberg Lofdal K. Statin treatment reduces the risk of hepatocellular carcinoma but not colon cancer-results from a nationwide case-control study in Sweden. Pharmacoepidemiology and drug safety 2014; 23(10): 1101-6.
[15]	Leung HW, Chan AL, Lo D, et al. Common cancer risk and statins: a population-based case-control study in a Chinese population. Expert opinion on drug safety 2013; 12(1): 19-27.
[16]	Chaiteerakij R, Yang JD, Harmsen WS, et al. Risk factors for intrahepatic cholangiocarcinoma: association between metformin use and reduced cancer risk. Hepatology (Baltimore, Md) 2013; 57(2): 648-55.
[17]	Wells G, Shea B, O’connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2000.
[18]	Friis S, Poulsen AH, Johnsen SP, et al. Cancer risk among statin users: a population-based cohort study. International journal of cancer Journal international du cancer 2005; 114(4): 643-7.
[19]	El-Serag HB, Johnson ML, Hachem C, et al. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology 2009; 136(5): 1601-8.
[20]	Matsushita Y, Sugihara M, Kaburagi J, et al. Pravastatin use and cancer risk: a meta-analysis of individual patient data from long-term prospective controlled trials in Japan. Pharmacoepidemiology and drug safety 2010; 19(2): 196-202.
[21]	Chiu HF, Ho SC, Chen CC, et al. Statin use and the risk of liver cancer: a population-based case-control study. The American journal of gastroenterology 2011; 106(5): 894-8.
[22]	Marelli C, Gunnarsson C, Ross S, et al. Statins and risk of cancer: a retrospective cohort analysis of 45,857 matched pairs from an electronic medical records database of 11 million adult Americans. Journal of the American College of Cardiology 2011; 58(5): 530-7.
[23]	Tsan YT, Lee CH, Wang JD, et al. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2012; 30(6): 623-30.
[24]	Wu J, Wong WW, Khosravi F, et al. Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukemia cells to lovastatin-induced apoptosis. Cancer research 2004; 64(18): 6461-8.
[25]	Rao S, Porter DC, Chen X, et al. Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proceedings of the National Academy of Sciences of the United States of America 1999; 96(14): 7797-802.
[26]	Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nature reviews Cancer 2006; 6(9): 674-87.
[27]	Shimizu M, Yasuda Y, Sakai H, et al. Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice. BMC cancer 2011; 11: 281.
[28]	Argo CK, Loria P, Caldwell SH, et al. Statins in liver disease: a molehill, an iceberg, or neither? Hepatology (Baltimore, Md) 2008; 48(2): 662-9.
[29]	Tu K, Liu Z, Yao B et al. MicroRNA-519a promotes tumor growth by targeting PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Int J Oncol 2015.
[30]	Chen YQ, Zhao LY, Zhang WZ, Li T. Simvastatin reverses cardiomyocyte hypertrophy via the upregulation of phosphatase and tensin homolog expression. Exp Ther Med 2015; 10: 797-803.
[31]	Murakami Y, Saigo K, Takashima H, et al. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut 2005; 54(8): 1162-8.
[32]	Tarn C, Lee S, Hu Y, et al. Hepatitis B virus X protein differentially activates RAS-RAF-MAPK and JNK pathways in X-transforming versus non-transforming AML12 hepatocytes. The Journal of biological chemistry 2001; 276(37): 34671-80.
[33]	Li ZH, Tang QB, Wang J, et al. Hepatitis C virus core protein induces malignant transformation of biliary epithelial cells by activating nuclear factor-kappaB pathway. Journal of gastroenterology and hepatology 2010; 25(7): 1315-20.
[34]	Higgs MR, Lerat H, Pawlotsky JM. Downregulation of Gadd45beta expression by hepatitis C virus leads to defective cell cycle arrest. Cancer research 2010; 70(12): 4901-11.
[35]	Weis M, Heeschen C, Glassford AJ, et al. Statins have biphasic effects on angiogenesis. Circulation 2002; 105(6): 739-45.
[36]	Bergmann OM, Kristjansson G, Jonasson JG, Bjornsson ES. Jaundice due to suspected statin hepatotoxicity: a case series. Dig Dis Sci 2012; 57: 1959-1964.
[37]	Mihăilă R-G. Statins in Chronic Hepatitis C: Stage result. Biomedical Research 2014; 25: 463-469.
[38]	Lonardo A, Loria P. Potential for statins in the chemoprevention and management of hepatocellular carcinoma. J Gastroenterol Hepatol 2012; 27: 1654-1664.
[39]	Park HJ, Kong D, Iruela-Arispe L, et al. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA. Circulation research 2002; 91(2): 143-50.

Cite This Article

Plain Text BibTeX RIS

APA Style

De-Sen Xiang, Jing Zhang. (2016). Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Science Journal of Public Health, 4(2), 81-87. https://doi.org/10.11648/j.sjph.20160402.11

Copy | Download

ACS Style

De-Sen Xiang; Jing Zhang. Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Sci. J. Public Health 2016, 4(2), 81-87. doi: 10.11648/j.sjph.20160402.11

Copy | Download

AMA Style

De-Sen Xiang, Jing Zhang. Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Sci J Public Health. 2016;4(2):81-87. doi: 10.11648/j.sjph.20160402.11

Copy | Download

@article{10.11648/j.sjph.20160402.11,
  author = {De-Sen Xiang and Jing Zhang},
  title = {Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies},
  journal = {Science Journal of Public Health},
  volume = {4},
  number = {2},
  pages = {81-87},
  doi = {10.11648/j.sjph.20160402.11},
  url = {https://doi.org/10.11648/j.sjph.20160402.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sjph.20160402.11},
  abstract = {The relationship between statin use and the risk of hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to clarify this issue. Data on the relationship between statin use and the risk of HCC were collected through an electronic search of PubMed database. Summary odds ratios (ORs) with 95% confidential intervals were calculated using a random-effects model. Six studies were selected for the final meta-analysis, involving 3778 cases and 482452 patients. Our meta-analysis showed that statin use was significantly associated with a decreased risk of HCC (OR, 0.60, 95% confidence interval, 0.48–0.76). In conclusion, the meta-analysis suggests that statin use is associated with a reduced risk of HCC. However, our findings should be interpreted with caution due to limited studies.},
 year = {2016}
}

Copy | Download

TY  - JOUR
T1  - Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies
AU  - De-Sen Xiang
AU  - Jing Zhang
Y1  - 2016/03/01
PY  - 2016
N1  - https://doi.org/10.11648/j.sjph.20160402.11
DO  - 10.11648/j.sjph.20160402.11
T2  - Science Journal of Public Health
JF  - Science Journal of Public Health
JO  - Science Journal of Public Health
SP  - 81
EP  - 87
PB  - Science Publishing Group
SN  - 2328-7950
UR  - https://doi.org/10.11648/j.sjph.20160402.11
AB  - The relationship between statin use and the risk of hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to clarify this issue. Data on the relationship between statin use and the risk of HCC were collected through an electronic search of PubMed database. Summary odds ratios (ORs) with 95% confidential intervals were calculated using a random-effects model. Six studies were selected for the final meta-analysis, involving 3778 cases and 482452 patients. Our meta-analysis showed that statin use was significantly associated with a decreased risk of HCC (OR, 0.60, 95% confidence interval, 0.48–0.76). In conclusion, the meta-analysis suggests that statin use is associated with a reduced risk of HCC. However, our findings should be interpreted with caution due to limited studies.
VL  - 4
IS  - 2
ER  -

Copy | Download

Author Information

De-Sen Xiang

Department of General Surgery, Qianjiang Central Hospital of Chongqing Municipality, Chongqing, China
Jing Zhang

Department of General Surgery, Qianjiang Central Hospital of Chongqing Municipality, Chongqing, China

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

De-Sen Xiang, Jing Zhang. (2016). Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Science Journal of Public Health, 4(2), 81-87. https://doi.org/10.11648/j.sjph.20160402.11

Copy | Download

ACS Style

De-Sen Xiang; Jing Zhang. Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Sci. J. Public Health 2016, 4(2), 81-87. doi: 10.11648/j.sjph.20160402.11

Copy | Download

AMA Style

De-Sen Xiang, Jing Zhang. Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Sci J Public Health. 2016;4(2):81-87. doi: 10.11648/j.sjph.20160402.11

Copy | Download

@article{10.11648/j.sjph.20160402.11,
  author = {De-Sen Xiang and Jing Zhang},
  title = {Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies},
  journal = {Science Journal of Public Health},
  volume = {4},
  number = {2},
  pages = {81-87},
  doi = {10.11648/j.sjph.20160402.11},
  url = {https://doi.org/10.11648/j.sjph.20160402.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sjph.20160402.11},
  abstract = {The relationship between statin use and the risk of hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to clarify this issue. Data on the relationship between statin use and the risk of HCC were collected through an electronic search of PubMed database. Summary odds ratios (ORs) with 95% confidential intervals were calculated using a random-effects model. Six studies were selected for the final meta-analysis, involving 3778 cases and 482452 patients. Our meta-analysis showed that statin use was significantly associated with a decreased risk of HCC (OR, 0.60, 95% confidence interval, 0.48–0.76). In conclusion, the meta-analysis suggests that statin use is associated with a reduced risk of HCC. However, our findings should be interpreted with caution due to limited studies.},
 year = {2016}
}

Copy | Download

TY  - JOUR
T1  - Association Between Statin Use and Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies
AU  - De-Sen Xiang
AU  - Jing Zhang
Y1  - 2016/03/01
PY  - 2016
N1  - https://doi.org/10.11648/j.sjph.20160402.11
DO  - 10.11648/j.sjph.20160402.11
T2  - Science Journal of Public Health
JF  - Science Journal of Public Health
JO  - Science Journal of Public Health
SP  - 81
EP  - 87
PB  - Science Publishing Group
SN  - 2328-7950
UR  - https://doi.org/10.11648/j.sjph.20160402.11
AB  - The relationship between statin use and the risk of hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to clarify this issue. Data on the relationship between statin use and the risk of HCC were collected through an electronic search of PubMed database. Summary odds ratios (ORs) with 95% confidential intervals were calculated using a random-effects model. Six studies were selected for the final meta-analysis, involving 3778 cases and 482452 patients. Our meta-analysis showed that statin use was significantly associated with a decreased risk of HCC (OR, 0.60, 95% confidence interval, 0.48–0.76). In conclusion, the meta-analysis suggests that statin use is associated with a reduced risk of HCC. However, our findings should be interpreted with caution due to limited studies.
VL  - 4
IS  - 2
ER  -

Copy | Download