Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 7/2011

01-07-2011 | Original Paper

Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review

Authors: Fei Jin, Wen-Jian Xiong, Jia-Chen Jing, Zhen Feng, Li-Shuai Qu, Xi-Zhong Shen

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2011

Login to get access

Abstract

Purpose

For decades of years, hundreds of candidate gene-based association studies explored the relationship between single nucleotide polymorphisms (SNPs) and hepatocellular carcinoma (HCC). There was no systematic review summarized the results of these association studies of candidate SNPs and HCC to date. In order to summarize the results of the association studies, we conducted a concise systematic review.

Methods

By searching Pubmed database before October 2010, we reviewed all the association studies about candidate SNPs and HCC. If the eligible study number on a given SNP was more than three, we conducted a meta-analysis. We reported here only the overall positive-association results with statistical significance and evaluated the reliability of the associations by using false-positive report probability (FPRP) analysis and the Venice guidelines on genetic epidemiology studies.

Results

Six SNPs of five genes (rs1800562 of HFE, rs17868323 and rs11692021 of UGT1A7, rs2279744 of MDM2, rs1143627 of IL-1B, and rs4880 of MnSOD) showed overall significant associations with HCC. The eligible number of the studies varied from three to nine. Two SNPs (rs1800562 of HFE and rs2279744 of MDM2) passed the FPRP threshold (FPRP < 0.20). According to the Venice guidelines, the associations between the two SNPs (rs1800562 and rs2279744) and HCC were of moderate evidence.

Conclusions

Two SNPs (rs1800562 of HFE and rs2279744 of MDM2) were associated with HCC with moderate epidemiological evidence and deserve further study and additional biological and clinical assessment.
Literature
Akkiz H, Bayram S et al (2009) G-308A TNF-alpha polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: case-control study. Cancer Epidemiol 33(3–4):261–264PubMedCrossRef
Akkiz H, Sumbul AT et al (2010) MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population. Cancer Epidemiol 34(4): 448–452
Ballardini G, Groff P et al (1994) Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation. J Hepatol 20(2):218–222PubMedCrossRef
Beckman LE, Hagerstrand I et al (2000) Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma. Oncology 59(4):317–322PubMedCrossRef
Boige V, Castera L et al (2003) Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis. Gut 52(8):1178–1181PubMedCrossRef
Borentain P, Gerolami V et al (2007) DNA-repair and carcinogen-metabolising enzymes genetic polymorphisms as an independent risk factor for hepatocellular carcinoma in Caucasian liver-transplanted patients. Eur J Cancer 43(17):2479–2486PubMedCrossRef
Bougeard G, Baert-Desurmont S et al (2006) Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome. J Med Genet 43(6):531–533PubMedCrossRef
Bruzzi P, Green SB et al (1985) Estimating the population attributable risk for multiple risk factors using case-control data. Am J Epidemiol 122(5):904–914PubMed
Cauza E, Peck-Radosavljevic M et al (2003) Mutations of the HFE gene in patients with hepatocellular carcinoma. Am J Gastroenterol 98(2):442–447PubMedCrossRef
Chen CJ, Chen DS (2002) Interaction of hepatitis B virus, chemical carcinogen, and genetic susceptibility: multistage hepatocarcinogenesis with multifactorial etiology. Hepatology 36(5):1046–1049PubMedCrossRef
Chen CC, Yang SY et al (2005) Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma. Int J Epidemiol 34(6):1310–1318PubMedCrossRef
Dharel N, Kato N et al (2006) MDM2 promoter SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis C. Clin Cancer Res 12(16):4867–4871PubMedCrossRef
Dupont WD, Plummer WD Jr (1990) Power and sample size calculations. A review and computer program. Control Clin Trials 11(2):116–128PubMedCrossRef
Dupont WD, Plummer WD Jr (1998) Power and sample size calculations for studies involving linear regression. Control Clin Trials 19(6):589–601PubMedCrossRef
Egger M, Davey Smith G et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634PubMed
Ellervik C, Birgens H et al (2007) Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66, 000 cases and 226, 000 controls. Hepatology 46(4):1071–1080PubMedCrossRef
El-Omar EM, Carrington M et al (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404(6776):398–402PubMedCrossRef
Ezzikouri S, El Feydi AE et al (2008a) Genetic polymorphism in the manganese superoxide dismutase gene is associated with an increased risk for hepatocellular carcinoma in HCV-infected Moroccan patients. Mutat Res 649(1–2):1–6PubMed
Ezzikouri S, El Feydi AE et al (2008b) Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan population. Arch Med Res 39(2):236–241PubMedCrossRef
Ezzikouri S, El Feydi AE et al (2009) MDM2 SNP309T > G polymorphism and risk of hepatocellular carcinoma: a case-control analysis in a Moroccan population. Cancer Detect Prev 32(5–6):380–385PubMedCrossRef
Guillemette C (2003) Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J 3(3):136–158PubMedCrossRef
Hellerbrand C, Poppl A et al (2003) HFE C282Y heterozygosity in hepatocellular carcinoma: evidence for an increased prevalence. Clin Gastroenterol Hepatol 1(4):279–284PubMedCrossRef
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558PubMedCrossRef
Hsieh JK, Chan FS et al (1999) RB regulates the stability and the apoptotic function of p53 via MDM2. Mol Cell 3(2):181–193PubMedCrossRef
Imaizumi T, Higaki Y et al (2009) Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population. Carcinogenesis 30(10):1729–1734PubMedCrossRef
Ioannidis JP, Boffetta P et al (2008) Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol 37(1):120–132PubMedCrossRef
Jin F, Qu LS et al (2009) Association between the methylenetetrahydrofolate reductase C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis. Diagn Pathol 4:39PubMedCrossRef
Jin F, Qu LS et al (2010) Association between C282Y and H63D mutations of the HFE gene with hepatocellular carcinoma in European populations: a meta-analysis. J Exp Clin Cancer Res 29:18
Kong SY, Ki CS et al (2008) UGT1A7 haplotype is associated with an increased risk of hepatocellular carcinoma in hepatitis B carriers. Cancer Sci 99(2):340–344PubMedCrossRef
Lain S, Lane D (2003) Improving cancer therapy by non-genotoxic activation of p53. Eur J Cancer 39(8):1053–1060PubMedCrossRef
Lau J, Ioannidis JP et al (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127(9):820–826PubMed
Lauret E, Rodriguez M et al (2002) HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma. Am J Gastroenterol 97(4):1016–1021PubMedCrossRef
Leu JD, Lin IF et al (2009) Association between MDM2-SNP309 and hepatocellular carcinoma in Taiwanese population. World J Gastroenterol 15(44):5592–5597PubMedCrossRef
Michael D, Oren M (2003) The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol 13(1):49–58PubMedCrossRef
Migita K, Maeda Y et al (2007) Polymorphisms of interleukin-1beta in Japanese patients with hepatitis B virus infection. J Hepatol 46(3):381–386PubMedCrossRef
Nahon P, Sutton A et al (2005) Genetic dimorphism in superoxide dismutase and susceptibility to alcoholic cirrhosis, hepatocellular carcinoma, and death. Clin Gastroenterol Hepatol 3(3):292–298PubMedCrossRef
Nahon P, Sutton A et al (2007) Manganese superoxide dismutase dimorphism and iron overload, hepatocellular carcinoma, and death in hepatitis C virus-infected patients. Clin Gastroenterol Hepatol 5(5):630–635PubMedCrossRef
Nahon P, Sutton A et al (2008) Liver iron, HFE gene mutations, and hepatocellular carcinoma occurrence in patients with cirrhosis. Gastroenterology 134(1):102–110PubMedCrossRef
Nahon P, Sutton A et al (2009) Myeloperoxidase and superoxide dismutase 2 polymorphisms comodulate the risk of hepatocellular carcinoma and death in alcoholic cirrhosis. Hepatology 50(5):1484–1493PubMedCrossRef
Ognjanovic S, Yuan JM et al (2009) Genetic polymorphisms in the cytokine genes and risk of hepatocellular carcinoma in low-risk non-Asians of USA. Carcinogenesis 30(5):758–762PubMedCrossRef
Oh SS, Chang SC et al (2010) Single nucleotide polymorphisms of 8 inflammation-related genes and their associations with smoking-related cancers. Int J Cancer 127(9):2169–2182
Okamoto K, Ishida C et al (2010) The genotypes of IL-1 beta and MMP-3 are associated with the prognosis of HCV-related hepatocellular carcinoma. Intern Med 49(10):887–895
Ropero P, Briceno O et al (2007) The H63D mutation in the HFE gene is related to the risk of hepatocellular carcinoma. Rev Esp Enferm Dig 99(7):376–381PubMedCrossRef
Rossi L, Leveri M et al (2003) Genetic polymorphisms of steroid hormone metabolizing enzymes and risk of liver cancer in hepatitis C-infected patients. J Hepatol 39(4):564–570PubMedCrossRef
Sakamoto T, Higaki Y et al (2008) Interaction between interleukin-1beta -31T/C gene polymorphism and drinking and smoking habits on the risk of hepatocellular carcinoma among Japanese. Cancer Lett 271(1):98–104PubMedCrossRef
Shi WJ, Chen H et al (2005) Association of mutations of HFE gene and hepatocellular carcinoma following chronic hepatitis B. Zhonghua Gan Zang Bing Za Zhi 13(9):682–684PubMed
Silvestri L, Sonzogni L et al (2003) CYP enzyme polymorphisms and susceptibility to HCV-related chronic liver disease and liver cancer. Int J Cancer 104(3):310–317PubMedCrossRef
Stucker I, Loriot MA et al (2007) UDP-glucuronosyltransferase UGT1A7 genetic polymorphisms in hepatocellular carcinoma: a differential impact according to seropositivity of HBV or HCV markers? BMC Cancer 7:214PubMedCrossRef
Sun L, Konig IR et al (2009) Manganese superoxide dismutase (MnSOD) polymorphism, alcohol, cigarette smoking and risk of oesophageal cancer. Alcohol Alcohol 44(4):353–357PubMed
Sutton A, Imbert A et al (2005) The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics 15(5):311–319PubMedCrossRef
Sutton A, Nahon P et al (2006) Genetic polymorphisms in antioxidant enzymes modulate hepatic iron accumulation and hepatocellular carcinoma development in patients with alcohol-induced cirrhosis. Cancer Res 66(5):2844–2852PubMedCrossRef
Tanabe KK, Lemoine A et al (2008) Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA 299(1):53–60PubMedCrossRef
Thakkinstian A, McElduff P et al (2005) A method for meta-analysis of molecular association studies. Stat Med 24(9):1291–1306PubMedCrossRef
Tseng CS, Tang KS et al (2005) UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma risk and onset age. Am J Gastroenterol 100(8):1758–1763PubMedCrossRef
Vogel A, Kneip S et al (2001) Genetic link of hepatocellular carcinoma with polymorphisms of the UDP-glucuronosyltransferase UGT1A7 gene. Gastroenterology 121(5):1136–1144PubMedCrossRef
Wacholder S, Chanock S et al (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96(6):434–442PubMedCrossRef
Wang Y, Kato N et al (2004) UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma in japanese patients with hepatitis C virus infection. Clin Cancer Res 10(7):2441–2446PubMedCrossRef
Wang S, Wang F et al (2009) Association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and cancer risk - A meta-analysis. Eur J Cancer 45(16):2874–2881PubMedCrossRef
Willis G, Bardsley V et al (2005) Hepatocellular carcinoma and the penetrance of HFE C282Y mutations: a cross sectional study. BMC Gastroenterol 5:17PubMedCrossRef
Yoon YJ, Chang HY et al (2008) MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis 29(6):1192–1196PubMedCrossRef
Yoshimura A (2006) Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 97(6):439–447PubMedCrossRef
Yuan JM, Lu SC et al (2007) Genetic polymorphisms in the methylenetetrahydrofolate reductase and thymidylate synthase genes and risk of hepatocellular carcinoma. Hepatology 46(3):749–758PubMedCrossRef
Yuan X, Zhou G et al (2008) Lack of association between the functional polymorphisms in the estrogen-metabolizing genes and risk for hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 17(12):3621–3627PubMedCrossRef
Zintzaras E, Ioannidis JP (2005) Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol 28(2):123–137PubMedCrossRef
Metadata
Title
Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review
Authors
Fei Jin
Wen-Jian Xiong
Jia-Chen Jing
Zhen Feng
Li-Shuai Qu
Xi-Zhong Shen
Publication date
01-07-2011
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 7/2011
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-010-0970-0

Other articles of this Issue 7/2011

Journal of Cancer Research and Clinical Oncology 7/2011 Go to the issue

Original Paper

Prognostic and predictive relevance of CA-125 at primary surgery of ovarian cancer

Original Paper

IL-8-251A>T polymorphism is associated with breast cancer risk: a meta-analysis

Review

The influence of family history and histological stratification on breast cancer risk in women with benign breast disease: a meta-analysis

Original Paper

Treatment of advanced non-small-cell lung cancer with Chinese herbal medicine by stages combined with chemotherapy

Original Paper

Identification of vitronectin as a novel serum marker for early breast cancer detection using a new proteomic approach

Original Paper

Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive human colorectal cancer
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits