Skip to main content
SpringerLink
Log in

P53 codon 249 mutation and other risk factors among Nigerians with hepatocellular carcinoma

Mutation du codon 249 de P53 et autres facteurs de risque chez des Nigérians atteints de carcinome hépatocellulaire

  • Original Article / Article Original
  • Published:
Journal Africain du Cancer / African Journal of Cancer

Abstract

Aim

We aimed to study the prevalence of major risk factors for hepatocellular carcinoma (HCC) among Nigerians.

Method

Eighty-five HCC patients and 77 non-HCC, nonchronic liver diseased age and gender-matched controls were recruited. The p53 codon 249mutationwas detected by restriction fragment length polymorphism (RFLP) using plasma DNA. HBV and HCV infection were detected by thirdgeneration enzyme-linked immunosorbent assay (ELISA) technique in 55 HCC subjects and 52 controls. Alcohol intake was obtained from the history of the subjects, and significant alcohol ingestion was taken as ingestion of ≥40 g daily of alcohol for ≥10 years.

Results

The prevalence of the p53 codon 249 mutation, positive HBsAg status, anti-HCV, and significant alcohol ingestion among HCC patients were 7.6 (6/79), 58.2 (32/55), 6.0 (3/50), and 38.5% (30/78), respectively, versus 0 (0/73), 7.7 (4/52), 11.5 (6/52), and 13.3% (10/77), respectively among controls. The respective p values were 0.029, 0.000, 0.182, and 0.005. The odds ratio were 2.00 (95% CI: 1.70–2.35), 16.7 (95% CI = 5.276–52.857), 0.489 (95% CI = 0.115–2.073), and 4.186 (95% CI = 1.870–10.372), respectively.

Conclusion

p53 codon 249 mutation, HBV infection, and alcohol are significantly associated with HCC in Nigeria, whereas HCV infection is not.

Résumé

But de l’étude

Nous avons voulu étudier la prévalence des facteurs de risque majeurs de carcinome hépatocellulaire (CHC) chez les Nigérians.

Méthodes

Quatre-vingt-cinq patients atteints de CHC et 77 témoins non atteints de CHC ni de maladie hépatique chronique, comparables par l’âge et le sexe, ont été recrutés. La mutation du codon 249 de P53 a été détectée par RFLP (polymorphisme de longueur des fragments de restriction) sur de l’ADN plasmatique. L’infection par le VHB et le VHC a été détectée par une technique ELISA de troisième génération chez 55 sujets avec CHC et 52 témoins. La consommation d’alcool a été déterminée par l’anamnèse et elle était jugée significative lorsqu’elle était ≥ 40 g/jour d’alcool pendant ≥ 10 ans.

Résultats

La prévalence de la mutation du codon 249 de p53, de la présence d’antigène HBs (AgHBs+), de la présence d’anticorps anti-VHC et d’une consommation significative d’alcool chez les patients atteints de CHC était respectivement de 7,6 % (6/79), 58,2 % (32/55), 6,0 % (3/50) et 38,5 % (30/78), contre respectivement 0 % (0/73), 7,7 % (4/52), 11,5 % (6/52) et 13,3 % (10/77) chez les témoins. Les valeurs de p respectives étaient de 0,029, 0,000, 0,182 et 0,005. Les rapports de cotes étaient respectivement de 2,00 (IC 95 % = 1,70–2,35), 16,7 (IC 95 %= 5,276–52,857), 0,489 (IC 95 % = 0,115–2,073) et 4,186 (IC 95 % = 1,870–10,372).

Conclusion

La mutation du codon 249 de P53, l’infection par le VHB et l’alcool montrent une association significative avec le CHC au Nigeria, mais pas l’infection par le VHC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Olubuyide IO, Aliyu B, Olaleye OA, et al (1997) Hepatitis B and C virus and hepatocellular carcinoma. Transactions of the Royal Society of Trop Med and Hyg 91:38–41

    Article  CAS  Google Scholar 

  2. Gashau W, Mohammed I (1991) Hepatitis B viral markers in Nigerian patients with primary liver cell carcinoma. Trop and Geog Med 43:64–67

    CAS  Google Scholar 

  3. Olubuyide IO (1992) Natural history of primary liver cell carcinoma. A study of 89 untreated adult Nigerians. Centr Afr J Med. 38:25–30

    CAS  Google Scholar 

  4. Kirk GD, Lesi OA, Mendy M, et al (2005) 249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 24:5858–5867

    Article  CAS  PubMed  Google Scholar 

  5. Coursaget P, Bourdil C, Kastally R, et al (1990) Prevalence of hepatitis C virus infection in Africa: anti-HCV antibodies in the general population and in patients suffering from cirrhosis or primary liver cancer. Res Virol 141:449–454

    Article  CAS  PubMed  Google Scholar 

  6. Bruix J, Sherman M, Llovet JM, et al (2001) Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference. J Hepatol 35:421–430

    Article  CAS  PubMed  Google Scholar 

  7. Jackson PE, Kuang SY, Wang JB, et al (2003) Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients. Carcinogenesis 24:1657–1663

    Article  CAS  PubMed  Google Scholar 

  8. Kirk GD, Camus-Randon AM, Mendy M, et al (2000) Ser-249 p53 Mutations in Plasma DNA of Patients With Hepatocellular Carcinoma From The Gambia. Journal of the National Cancer Institute 92:148–153

    Article  CAS  PubMed  Google Scholar 

  9. Ming L, Thorgeirsson S, Gail M, et al (2002) Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China. Hepatology 36:1214–1220

    Article  CAS  PubMed  Google Scholar 

  10. Stern MC, Umbach DM, Yu CM, et al (2001) Hepatitis B, Aflatoxin B1, and p53 Codon 249 Mutation in Hepatocellular Carcinomas from Guangxi, People’s Republic of China, and a Meta-analysis of Existing Studies. Cancer Epidemiology Biomarkers & Prevention 10:617–625

    CAS  Google Scholar 

  11. Coursaget P, Depril N, Chabaud M, et al (1993) High prevalence of mutations at codon 249 of the P53 gene in hepatocellular carcinomas from Senegal. Br J Cancer 67:1395–1397

    CAS  PubMed  Google Scholar 

  12. Ndububa DA, Yakicier CM, Ojo OS, et al (2001) P53 codon 249 mutation in Hepatocellular carcinomas from Nigeria. Afr J Med and Med Sci 30:125–127

    CAS  Google Scholar 

  13. Anker P, Mulcahy H, Chen XQ, Stroun M (1999) Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev 18:65–73

    Article  CAS  PubMed  Google Scholar 

  14. Lleonart ME, Kirk GD, Vilar S, et al (2005) Quantitative Analysis of Plasma TP53 249ser-Mutated DNA by Electrospray IonisationMass Spectrometry. Cancer Epidemiol Biomarkers Prev 14:2956–2962

    Article  CAS  PubMed  Google Scholar 

  15. Nwokolo C, Okonkwo I (1978) Aflatoxin load of common food in savanna and forest regions of Nigeria. Transactions of the Royal Society of Trop Med and Hyg 72:329–332

    Article  CAS  Google Scholar 

  16. Bababunmi EA, Uwaifo AO, Bassir O (1978) Hepatocarcinogens in Nigerian Foodstuffs. Wld Rev Nutr Diet 28:188–209

    CAS  Google Scholar 

  17. Atawodi SE, Atiku AA, Lamorde AG (1993) Aflatoixn contamination of Nigerian foods and feeding stuffs. Fd Chem Toxic 32:61–63

    Article  Google Scholar 

  18. Olubuyide IO, Maxwell SM, Akinyinka OO, et al (1993) HBsAg and aflatoxins in sera of rural (Igbo-Ora) and urban (Ibadan) populations in Nigeria. Afr J Med med Sci 22:77–80

    CAS  PubMed  Google Scholar 

  19. McGlynn KA, Rosevold EA, Lustbader ED, et al (1995) Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. Proc Natl Acad Sci USA 92:2384–2387.

    Article  CAS  PubMed  Google Scholar 

  20. Beasely RP, Hwang LY, Lin CC, Chien CS (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective Study of 22,707 Men in Taiwan. Lancet 2:1129–1132

    Article  Google Scholar 

  21. Ding X, Park YM, Taltavull TC, et al (2003) Geographic Characterisation of Hepatitis Virus Infections, Genotyping of Hepatitis B Virus, and p53 Mutation in Hepatocellular Carcinoma Analysed by In Situ Detection of Viral Genomes from Carcinoma Tissues: Comparison among Six Different Countries. Jpn J Infect Dis 56:12–18

    CAS  PubMed  Google Scholar 

  22. Coursaget P, Maupas P, Goudeau A, et al (1981) A case/control study of hepatitis B virus serologic markers in Senegalese patients suffering from primary hepatocellular carcinoma. Prog Med Virol 27:49–59

    CAS  PubMed  Google Scholar 

  23. Kirk GD, Lesi OA, Mendy M, et al (2004) The Gambia Liver Cancer Study: Infection With Hepatitis B and C and the Risk of Hepatocellular Carcinoma in West Africa. Hepatology 39:211–219

    Article  PubMed  Google Scholar 

  24. Chen CJ, Liang KY, Chang AS, et al (1991) Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma. Hepatology 13:398–406

    Article  CAS  PubMed  Google Scholar 

  25. Ndububa DA, Ojo OS, Adeodu OO et al (2001) Primary Hepatocellular Carcinoma in Ile-Ife, Nigeria: A Prospective Study of 154 Cases. Nig J Med 10:59–63

    CAS  Google Scholar 

  26. Olubuyide IO, Bamgboye EA (1990) A case-controlled study of the current role of cigarette smoking and alcohol consumption in primary liver cell carcinoma in Nigerians. Afr J Med Med Sci 19:191–194

    CAS  PubMed  Google Scholar 

  27. Lesi OA, Kehinde MO, Anomneze EE., Wali SS (2002) Hepatitis C Infection And Risk Of Chronic Liver Disease In Lagos. Nig. Ot J. Hosp Med 12:1–5

    Google Scholar 

  28. James CM (1994) The Liver and the Biliary Tract. In: Robins. Pathologic Basis of Disease. Philadelphia: W.B. Saunders (Publishers) Company, pp 879

    Google Scholar 

  29. Mutimer DJ, Olomu A Skidmore S, et al (1994) Viral hepatitis in Nigeria — sickle-cell disease and commercial blood donors. Quarterly Journal of Medicine 87:407–411

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medicine Department, Lagos State University College of Medicine, Ikeja, Lagos state

    R. Igetei

  2. Medicine Department, University College Hospital, Ibadan, Nigeria

    J. A. Otegbayo

  3. Medicine Department, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria

    O. A. Lesi

  4. Zoology Department, University of Ibadan, Ibadan, Nigeria

    C. I. Anumudu

  5. Medicine Department, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria

    D. A. Ndububa

Authors
  1. R. Igetei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. A. Otegbayo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. A. Lesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. I. Anumudu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. A. Ndububa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Igetei.

About this article

Cite this article

Igetei, R., Otegbayo, J.A., Lesi, O.A. et al. P53 codon 249 mutation and other risk factors among Nigerians with hepatocellular carcinoma. J Afr Cancer 2, 133–139 (2010). https://doi.org/10.1007/s12558-010-0083-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12558-010-0083-3

Keywords

Mots clés

Search

Navigation