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 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Infectious Agents and Cancer
Published in: Infectious Agents and Cancer 1/2011

Open Access 01-12-2011 | Research Article

TP 53 and MDM2 gene polymorphisms and risk of hepatocellular carcinoma among Italian patients

Authors: Valeria Di Vuolo, Luigi Buonaguro, Francesco Izzo, Simona Losito, Gerardo Botti, Franco M Buonaguro, Maria Lina Tornesello

Published in: Infectious Agents and Cancer | Issue 1/2011

Login to get access

Abstract

Background

Single-nucleotide polymorphisms within TP 53 gene (codon 72 exon 4, rs1042522, encoding either arginine or proline) and MDM2 promoter (SNP309; rs2279744), have been independently associated with increased risk of several cancer types. Few studies have analysed the role of these polymorphisms in the development of hepatocellular carcinoma.

Methods

Genotype distribution of TP 53 codon 72 and MDM2 SNP309 in 61 viral hepatitis-related hepatocellular carcinoma cases and 122 blood samples (healthy controls) from Italian subjects were determined by PCR and restriction fragment length polymorphism (RFLP).

Results

Frequencies of TP 53 codon 72 alleles were not significantly different between cases and controls. A significant increase of MDM2 SNP309 G/G and T/G genotypes were observed among hepatocellular carcinoma cases (Odds Ratio, OR = 3.56, 95% Confidence Limits, 95% CI = 1.3-9.7; and OR = 2.82, 95% CI = 1.3-6.4, respectively).

Conclusions

These results highlight a significant role of MDM2 SNP309 G allele as a susceptibility gene for the development of viral hepatitis-related hepatocellular carcinoma among Italian subjects.
Appendix
Available only for authorised users
Literature
1.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 2. Int J Cancer. 2010
2.
Cho LY, Yang JJ, Ko KP, Park B, Shin A, Lim MK, et al: Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: systematic review and meta-analysis 2. Int J Cancer. 2011, 128: 176-184. 10.1002/ijc.25321.PubMedCrossRef
3.
Okuda K, Fujimoto I, Hanai A, Urano Y: Changing incidence of hepatocellular carcinoma in Japan. Cancer Res. 1987, 47: 4967-4972.PubMed
4.
Deuffic S, Poynard T, Buffat L, Valleron AJ: Trends in primary liver cancer. Lancet. 1998, 351: 214-215.PubMedCrossRef
5.
Taylor-Robinson SD, Foster GR, Arora S, Hargreaves S, Thomas HC: Increase in primary liver cancer in the UK, 1979-94. Lancet. 1997, 350: 1142-1143.PubMedCrossRef
6.
El-Serag HB, Davila JA, Petersen NJ, McGlynn KA: The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med. 2003, 139: 817-823.PubMedCrossRef
7.
Chuang SC, La VC, Boffetta P: Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection 1. Cancer Lett. 2009, 286: 9-14. 10.1016/j.canlet.2008.10.040.PubMedCrossRef
8.
Donato F, Gelatti U, Limina RM, Fattovich G: Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence 1. Oncogene. 2006, 25: 3756-3770. 10.1038/sj.onc.1209557.PubMedCrossRef
9.
Tsukuma H, Hiyama T, Oshima A, Sobue T, Fujimoto I, Kasugai H, et al: A case-control study of hepatocellular carcinoma in Osaka, Japan. Int J Cancer. 1990, 45: 231-236. 10.1002/ijc.2910450205.PubMedCrossRef
10.
Romeo R, Colombo M: The natural history of hepatocellular carcinoma. Toxicology. 2002, 181-182: 39-42.PubMedCrossRef
11.
Fusco M, Girardi E, Piselli P, Palombino R, Polesel J, Maione C, et al: Epidemiology of viral hepatitis infections in an area of southern Italy with high incidence rates of liver cancer. Eur J Cancer. 2008, 44: 847-853. 10.1016/j.ejca.2008.01.025.PubMedCrossRef
12.
Matlashewski GJ, Tuck S, Pim D, Lamb P, Schneider J, Crawford LV: Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol. 1987, 7: 961-963.PubMedPubMedCentralCrossRef
13.
Pietsch EC, Humbey O, Murphy ME: Polymorphisms in the p53 pathway. Oncogene. 2006, 25: 1602-1611. 10.1038/sj.onc.1209367.PubMedCrossRef
14.
Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, et al: A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004, 119: 591-602. 10.1016/j.cell.2004.11.022.PubMedCrossRef
15.
Bougeard G, Baert-Desurmont S, Tournier I, Vasseur S, Martin C, Brugieres L, et al: Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome. J Med Genet. 2006, 43: 531-533. 10.1136/jmg.2005.037952.PubMedPubMedCentralCrossRef
16.
Ruijs MW, Schmidt MK, Nevanlinna H, Tommiska J, Aittomaki K, Pruntel R, et al: The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the Li-Fraumeni syndrome and related phenotypes. Eur J Hum Genet. 2007, 15: 110-114. 10.1038/sj.ejhg.5201715.PubMedCrossRef
17.
Bond GL, Hirshfield KM, Kirchhoff T, Alexe G, Bond EE, Robins H, et al: MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res. 2006, 66: 5104-5110. 10.1158/0008-5472.CAN-06-0180.PubMedCrossRef
18.
Yoon YJ, Chang HY, Ahn SH, Kim JK, Park YK, Kang DR, et al: MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection 1. Carcinogenesis. 2008, 29: 1192-1196. 10.1093/carcin/bgn090.PubMedCrossRef
19.
Tornesello ML, Duraturo ML, Waddell KM, Biryahwaho B, Downing R, Balinandi S, et al: Evaluating the role of human papillomaviruses in conjunctival neoplasia. Br J Cancer. 2006, 94: 446-449. 10.1038/sj.bjc.6602921.PubMedPubMedCentralCrossRef
20.
Tornesello ML, Biryahwaho B, Downing R, Hatzakis A, Alessi E, Cusini M, et al: TP53 codon 72 polymorphism in classic, endemic and epidemic Kaposi's sarcoma in African and Caucasian patients. Oncology. 2009, 77: 328-334. 10.1159/000260905.PubMedCrossRef
21.
Tornesello ML, Buonaguro L, Cristillo M, Biryahwaho B, Downing R, Hatzakis A, et al: MDM2 and CDKN1A gene polymorphisms and risk of Kaposi's sarcoma in African and Caucasian patients. Biomarkers. 2011, 16: 42-50. 10.3109/1354750X.2010.525664.PubMedCrossRef
22.
Hrstka R, Coates PJ, Vojtesek B: Polymorphisms in p53 and the p53 pathway: roles in cancer susceptibility and response to treatment. J Cell Mol Med. 2009, 13: 440-453. 10.1111/j.1582-4934.2008.00634.x.PubMedPubMedCentralCrossRef
23.
Whibley C, Pharoah PD, Hollstein M: p53 polymorphisms: cancer implications. Nat Rev Cancer. 2009, 9: 95-107. 10.1038/nrc2584.PubMedCrossRef
24.
Bonds L, Baker P, Gup C, Shroyer KR: Immunohistochemical localization of cdc6 in squamous and glandular neoplasia of the uterine cervix. Arch Pathol Lab Med. 2002, 126: 1164-1168.PubMed
25.
Menin C, Scaini MC, De Salvo GL, Biscuola M, Quaggio M, Esposito G, et al: Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer Inst. 2006, 98: 285-288. 10.1093/jnci/djj054.PubMedCrossRef
26.
Capasso M, Ayala F, Avvisati RA, Russo R, Gambale A, Mozzillo N, et al: MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness. J Hum Genet. 2010
27.
Bonafe M, Olivieri F, Mari D, Baggio G, Mattace R, Berardelli M, et al: P53 codon 72 polymorphism and longevity: additional data on centenarians from continental Italy and Sardinia. Am J Hum Genet. 1999, 65: 1782-1785. 10.1086/302664.PubMedPubMedCentralCrossRef
28.
Leveri M, Gritti C, Rossi L, Zavaglia C, Civardi E, Mondelli MU, et al: Codon 72 polymorphism of P53 gene does not affect the risk of cirrhosis and hepatocarcinoma in HCV-infected patients. Cancer Lett. 2004, 208: 75-79. 10.1016/j.canlet.2004.02.016.PubMedCrossRef
29.
Anzola M, Cuevas N, Lopez-Martinez M, Saiz A, Burgos JJ, de Pancorbo MM: Frequent loss of p53 codon 72 Pro variant in hepatitis C virus-positive carriers with hepatocellular carcinoma. Cancer Lett. 2003, 193: 199-205. 10.1016/S0304-3835(03)00046-6.PubMedCrossRef
30.
Ezzikouri S, El Feydi AE, Chafik A, Benazzouz M, El KL, Afifi R, et al: The Pro variant of the p53 codon 72 polymorphism is associated with hepatocellular carcinoma in Moroccan population. Hepatol Res. 2007, 37: 748-754. 10.1111/j.1872-034X.2007.00126.x.PubMedCrossRef
31.
Chen X, Liu F, Li B, Wei YG, Yan LN, Wen TF: p53 codon 72 polymorphism and liver cancer susceptibility: A meta-analysis of epidemiologic studies. World J Gastroenterol. 2011, 17: 1211-1218. 10.3748/wjg.v17.i9.1211.PubMedPubMedCentralCrossRef
32.
Yu MW, Yang SY, Chiu YH, Chiang YC, Liaw YF, Chen CJ: A p53 genetic polymorphism as a modulator of hepatocellular carcinoma risk in relation to chronic liver disease, familial tendency, and cigarette smoking in hepatitis B carriers. Hepatology. 1999, 29: 697-702. 10.1002/hep.510290330.PubMedCrossRef
33.
Dharel N, Kato N, Muroyama R, Moriyama M, Shao RX, Kawabe T, et al: MDM2 promoter SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis C. Clin Cancer Res. 2006, 12: 4867-4871. 10.1158/1078-0432.CCR-06-0111.PubMedCrossRef
34.
Leu JD, Lin IF, Sun YF, Chen SM, Liu CC, Lee YJ: Association between MDM2-SNP309 and hepatocellular carcinoma in Taiwanese population. World J Gastroenterol. 2009, 15: 5592-5597. 10.3748/wjg.15.5592.PubMedPubMedCentralCrossRef
35.
Ezzikouri S, El Feydi AE, Afifi R, El KL, Benazzouz M, Hassar M, et al: MDM2 SNP309T > G polymorphism and risk of hepatocellular carcinoma: a case-control analysis in a Moroccan population. Cancer Detect Prev. 2009, 32: 380-385. 10.1016/j.cdp.2009.01.003.PubMedCrossRef
36.
Akkiz H, Sumbul AT, Bayram S, Bekar A, Akgollu E: MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population. Cancer Epidemiol. 2010, 34: 448-452. 10.1016/j.canep.2010.04.008.PubMedCrossRef
37.
Jin F, Xiong WJ, Jing JC, Feng Z, Qu LS, Shen XZ: Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review. J Cancer Res Clin Oncol. 2011
38.
Arva NC, Gopen TR, Talbott KE, Campbell LE, Chicas A, White DE, et al: A chromatin-associated and transcriptionally inactive p53-Mdm2 complex occurs in mdm2 SNP309 homozygous cells 1. J Biol Chem. 2005, 280: 26776-26787. 10.1074/jbc.M505203200.PubMedCrossRef
39.
Bond GL, Hu W, Levine A: A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res. 2005, 65: 5481-5484. 10.1158/0008-5472.CAN-05-0825.PubMedCrossRef
40.
Michael D, Oren M: The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003, 13: 49-58. 10.1016/S1044-579X(02)00099-8.PubMedCrossRef
41.
Hirata H, Hinoda Y, Kikuno N, Kawamoto K, Suehiro Y, Tanaka Y, et al: MDM2 SNP309 polymorphism as risk factor for susceptibility and poor prognosis in renal cell carcinoma. Clin Cancer Res. 2007, 13: 4123-4129. 10.1158/1078-0432.CCR-07-0609.PubMedCrossRef
42.
Mendrysa SM, McElwee MK, Michalowski J, O'Leary KA, Young KM, Perry ME: mdm2 Is critical for inhibition of p53 during lymphopoiesis and the response to ionizing irradiation. Mol Cell Biol. 2003, 23: 462-472. 10.1128/MCB.23.2.462-473.2003.PubMedPubMedCentralCrossRef
43.
Gong GZ, Jiang YF, He Y, Lai LY, Zhu YH, Su XS: HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding. World J Gastroenterol. 2004, 10: 2223-2227.PubMedPubMedCentral
44.
Siavoshian S, Abraham JD, Kieny MP, Schuster C: HCV core, NS3, NS5A and NS5B proteins modulate cell proliferation independently from p53 expression in hepatocarcinoma cell lines. Arch Virol. 2004, 149: 323-336. 10.1007/s00705-003-0205-7.PubMedCrossRef
45.
Lan KH, Sheu ML, Hwang SJ, Yen SH, Chen SY, Wu JC, et al: HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene. 2002, 21: 4801-4811. 10.1038/sj.onc.1205589.PubMedCrossRef
Metadata
Title
TP 53 and MDM2 gene polymorphisms and risk of hepatocellular carcinoma among Italian patients
Authors
Valeria Di Vuolo
Luigi Buonaguro
Francesco Izzo
Simona Losito
Gerardo Botti
Franco M Buonaguro
Maria Lina Tornesello
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Infectious Agents and Cancer / Issue 1/2011
Electronic ISSN: 1750-9378
DOI
https://doi.org/10.1186/1750-9378-6-13

Other articles of this Issue 1/2011

Infectious Agents and Cancer 1/2011 Go to the issue

Research Article

A population-based cross-sectional study of age-specific risk factors for high risk human papillomavirus prevalence in rural Nigeria

Research article

Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein

Research article

HPV types, HIV and invasive cervical carcinoma risk in Kampala, Uganda: a case-control study

Research article

Performance of the digene LQ, RH and PS HPVs genotyping systems on clinical samples and comparison with HC2 and PCR-based Linear Array

Research Article

Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV) in Ugandan women

Research article

A case-cohort study of human herpesvirus 8 seropositivity and incident prostate cancer in Tobago

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits