249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma.
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 (249(ser); 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 249(ser) 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 249(ser) 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 249(ser) 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), 249(ser) 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.
Kirk
Gregory D
GD
Gambia Hepatitis Intervention Study, Banjul. gkirk@jhsph.edu
Lesi
Olufunmilayo A
OA
Mendy
Maimuna
M
Szymañska
Katarzyna
K
Whittle
Hilton
H
Goedert
James J
JJ
Hainaut
Pierre
P
Montesano
Ruggero
R
D000348:Aflatoxins / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000097:blood*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D000348:Aflatoxins; D004247:DNA