249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma

Gregory D. Kirk, Olufunmilayo A. Lesi, Maimuna Mendy, Katarzyna Szymañska, Hilton Whittle, James J. Goedert, Pierre Hainaut, Ruggero Montesano

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatocellular carcinoma (HCC) from regions with high dietary exposure to aflatoxins and endemic for hepatitis B virus (HBV) often contain a specific mutation at codon 249 in TP53 (249ser; AGG to AGT, Arg to Ser). This mutation is also detectable in circulating cell-free DNA from the plasma of HCC patients and healthy subjects in these regions. We have examined the joint effect of plasma 249ser and HBV infection in a case-control study design involving 348 control, 98 cirrhotic, and 186 HCC participants from The Gambia, West Africa, an area of high HCC incidence. The 249ser mutation was detected in 3.5% of controls, 15.3% of cirrhotics, and 39.8% of HCC cases (adjusted odds ratios (OR): 4.83, (95% confidence interval (CI): 1.71-13.7) for cirrhosis and 20.3 (8.19-50.0) for HCC). HBsAg positivity along with plasma 249ser was observed in 45/183 (24.6%) HCC cases compared to only one (0.3%) control. Risk for HCC was associated with markers of HBV alone (OR: 10.0, 95% CI: 5.16-19.6), 249ser alone (OR: 13.2, 95% CI: 4.99-35.0), and both markers present (OR: 399, 95% CI: 48.6-3270). These results suggest a multiplicative effect on HCC risk resulting from the mutational effect of aflatoxin on TP53, as monitored by detection of plasma 249 ser, with concomitant chronic infection with HBV.

Original languageEnglish (US)
Pages (from-to)5858-5867
Number of pages10
JournalOncogene
Volume24
Issue number38
DOIs
StatePublished - Sep 1 2005

Keywords

  • Aflatoxin
  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Plasma DNA
  • TP53 gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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