title: Interaction between p53 codon 72 and MDM2 309T>G polymorphisms and the risk of hepatocellular carcinoma.
abstract: The p53 tumor suppressor and its negative regulator, murine double minute 2 (MDM2), play critical roles in carcinogenesis. P53 codon 72 and MDM2 309T>G polymorphisms could influence p53 and MDM2 function, respectively, and might affect cancer susceptibility. We therefore investigated the association between these two SNPs, alone or in combination, and the risk of hepatocellular carcinoma (HCC) in Chinese. In this case-control study, we genotyped p53 codon 72 and MDM2 309T>G polymorphisms in 985 HCC cases and 992 cancer-free age- and sex-matched controls and evaluated their associations with the risk of HCC. Although no significant main effects were found for these two SNPs in the single-locus analysis and stratified analysis by age, sex, smoking, drinking, and hepatitis B virus (HBV) infection, we found that individuals carrying at least one G allele of the MDM2 309T>G polymorphism had statistically significant increased risk of HCC among those with the p53 Pro/Pro genotype (adjusted odds ratio (OR) = 2.23, 95 % confidence interval (95%CI) = 1.20-4.14 for TG genotype; adjusted OR = 2.67, 95%CI = 1.32-5.42 for GG genotype), and the interaction between p53 codon 72 and MDM2 309T>G was significant (P interaction = 0.017). Our findings suggest that the interaction of p53 codon 72 and MDM2 309T>G may play an important role in the etiology of HCC. More studies with well-designed and large sample sizes are required to validate these observations.
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, 15 Le qun Road, Guilin, 541001, China.
authors.forename: Moqin
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, 18 Jin zhou Road, Nanning, 530028, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Guilin Medical College, 109 Huan cheng Road, Guilin, 541004, China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Guilin Medical College, 109 Huan cheng Road, Guilin, 541004, China.
authors.forename: Linyuan
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Guilin Medical College, 109 Huan cheng Road, Guilin, 541004, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Bei
authors.affiliation: Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, 22 Shuang yong Road, Nanning, 530021, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, 22 Shuang yong Road, Nanning, 530021, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, 15 Le qun Road, Guilin, 541001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, 15 Le qun Road, Guilin, 541001, China.
authors.forename: Songqing
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Guilin Medical College, 109 Huan cheng Road, Guilin, 541004, China. yhp268@163.com.
authors.forename: Hongping
authors.initials: H
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Hepatocellular carcinoma; MDM2; Risk; Single-nucleotide polymorphism; p53