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

Oncogene volume 24, pages 5858–5867 (2005)Cite this article

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 249ser, with concomitant chronic infection with HBV.

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Acknowledgements

We would like to thank Yusupha Bah, Ebrima Bojang, Buba Sanyang, Lang Dampha, Ebou Njie, Adam Jeng, Joseph Bass, and Ebrima Bah for their support in the field and in the lab. The active participation of the staff at RVH, MRC, and BSG hospitals is greatly appreciated. TP53 mutation analysis was performed in Lyon by Elodie Derepierre and Stéphanie Michel, both supported by IARC Special Training Awards. Emmanuelle Gormally provided many technical suggestions and comments on the origin of cell-free plasma DNA. Chris Wild provided helpful comments regarding the analysis and the manuscript. Finally, the participation of the study participants is gratefully recognized. This study was supported in part by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services (Contract # N02CP40521).

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Authors and Affiliations

  1. Gambia Hepatitis Intervention Study, Banjul, The Gambia

    Gregory D Kirk, Olufunmilayo A Lesi, Maimuna Mendy, Hilton Whittle & Pierre Hainaut

  2. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, USA

    Gregory D Kirk

  3. Division of Cancer Epidemiology and Genetics, Viral Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA

    Gregory D Kirk & James J Goedert

  4. Medical Research Council Laboratories, Banjul, The Gambia

    Maimuna Mendy & Hilton Whittle

  5. International Agency for Research on Cancer, Lyon, France

    Katarzyna Szymañska, Pierre Hainaut & Ruggero Montesano

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Kirk, G., Lesi, O., Mendy, M. et al. 249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 24, 5858–5867 (2005). https://doi.org/10.1038/sj.onc.1208732

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