TY - JOUR
T1 - 249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma
AU - Kirk, Gregory D.
AU - Lesi, Olufunmilayo A.
AU - Mendy, Maimuna
AU - Szymañska, Katarzyna
AU - Whittle, Hilton
AU - Goedert, James J.
AU - Hainaut, Pierre
AU - Montesano, Ruggero
N1 - Funding Information:
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).
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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.
AB - 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.
KW - Aflatoxin
KW - Hepatitis B virus
KW - Hepatocellular carcinoma
KW - Plasma DNA
KW - TP53 gene
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U2 - 10.1038/sj.onc.1208732
DO - 10.1038/sj.onc.1208732
M3 - Article
C2 - 16007211
AN - SCOPUS:26944494627
VL - 24
SP - 5858
EP - 5867
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 38
ER -