Prevalence of aflatoxin induced p53 mutation at codon 249 (R249s) in hepatocellular carcinoma patients with and without hepatitis B surface antigen (HBsAg).
BACKGROUND
A missense mutation in exon 7 (R249S) of the p53 tumor suppressor gene is characteristic of aflatoxin B1 (AFB1) exposure. AFB1 is believed to have a synergistic effect on hepatitis virus B (HBV) carcinogenesis. However, results of studies comparing R249S prevalence among patients are conflicting. The aim of this study was to determine the prevalence of the R249S mutation in hepatocellular carcinoma (HCC) patients with or without positive HBsAg.


METHODS
Paraffin embedded liver tissues were obtained from 124 HCC patients who underwent liver resection and liver biopsy in King Chulalongkorn Memorial Hospital. Restriction fragment length polymorphism (RFLP) was utilized to detect the R249S mutation. Positive results were confirmed by direct sequencing.


RESULTS
Sixty four (52%) patients were positive for HBsAg and 18 (15%) were anti-HCV positive. 12 specimens tested positive by RFLP. Ten HCC patients (8.1%) were confirmed to be R249S positive by Sanger sequencing (AGG to AGT). Out of these 10, six were HBsAg positive, and out of the remaining 4, two were anti-HCV positive. The R249S prevalence among HCC patients with positive HBsAg was 9.4% compared to 6.7% for HBsAg negative samples. Patients with the R249S mutation were younger (55±10 vs 60±13 year-old) and tended to have a more advanced Edmonson-Steiner grade of HCC, although differences did not reach statistical significance.


CONCLUSIONS
Our study shows moderate prevalence of aflatoxin B1-related p53 mutation (R249S) in HCC with or without HBsAg. HBsAg positive status was not associated with R249S prevalence.
Liver Disease and Liver Cancer Research Unit, Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand E-mail : Yong.P@chula.ac.th.
Salyavit
S
Chittmittrapap
Thaweesak
T
Chieochansin
Roongruedee
R
Chaiteerakij
Sombat
S
Treeprasertsuk
Naruemon
N
Klaikaew
Pisit
P
Tangkijvanich
Piyawat
P
Komolmit
Yong
Y
Poovorawan
D000348:Aflatoxins / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000209:etiology* / Q000473:pathology; D004247:DNA / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011042:Poisons / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D011379:Prognosis; D012698:Serologic Tests; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000348:Aflatoxins; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011042:Poisons; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004247:DNA