[Association of p53 codon 72 polymorphism with genetic susceptibility to hepatocellular carcinoma in Chinese population].
OBJECTIVE
A functional single nucleotide polymorphism (SNP) at codon 72 of the gene for p53 protein (p53 R72P) has been implicated in a variety of human cancers, but the relationship between this SNP and hepatocellular carcinoma (HCC) remains obscure despite the fact that the critical role of p53 protein in HCC has been documented. This study was conducted to evaluate the link between the polymorphism with HCC stratified by chronic hepatitis B infection status in a Chinese population.


METHODS
Four hundred and sixty-nine HCC cases (359 HbsAg-positive, 110 HbsAg-negative) and 567 controls (137 HbsAg-positive, 430 HbsAg-negative) were studied. The p53 genotypes were determined by a PCR based restriction fragment length polymorphism (RFLP) method.


RESULTS
Overall, no correlation between HCC and the R72P genotypes was found when comparing all cases to controls or when comparing the HbsAg-positive HCC subgroup to controls. However, in HbsAg-negative subjects, the 72P allele was significantly associated with the presence of HCC (P=0.01) and had a higher risk (OR=1.69, 95% CI: 1.25-2.27) of HCC as compared to the 72R allele. By comparison to R/R homozygotes, the R/P heterozygotes and P/P homozygotes had a 1.73-fold (95% CI: 0.96-3.11) and a 3.29-fold (95% CI: 1.58-6.86) increased risk for HCC, respectively. The subjects with the 72P allele and a family history of HCC and those with the 72P allele and male gender also yielded an 11.14-fold (95% CI: 1.62-76.67) and a 9.39 fold (95% CI: 3.08-28.62) increased risk of HCC, respectively.


CONCLUSIONS
The P allele of the p53 R72P polymorphism has an increased risk for HCC in HbsAg-negative subjects, and exerts a synergistic influence on the risk for HCC when combined with HCC family history and the male gender.
Zhu
Zhong-zheng
ZZ
Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P. R. China.
Cong
Wen-ming
WM
Zhu
Guan-shan
GS
Liu
Shu-fang
SF
Xian
Zhi-hong
ZH
Wu
Wei-qing
WQ
Zhang
Xiu-zhong
XZ
Wang
Yan-hua
YH
Wu
Meng-chao
MC
D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics*; D002681:China; D003062:Codon / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D016159:Tumor Suppressor Protein p53