p53基因第72密码子多态性与中国人肝细胞癌遗传易感性的相关性  

Association of p53 codon 72 polymorphism with genetic susceptibility to hepatocellular carcinoma in Chinese population

作　　者：朱忠政[1] 丛文铭[1] 朱冠山[2] 刘淑芳[3] 冼志红[1] 吴伟清[1] 张秀忠[1] 王艳华[1] 吴孟超[1] 

机构地区：[1]第二军医大学东方肝胆外科医院病理科,上海200438 [2]第二军医大学长海医院感染科,上海200438 [3]上海同济大学铁路中心医院消化内科

出　　处：《中华医学遗传学杂志》2005年第6期632-635,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(30470791;30370645);上海市卫生系统百名优秀跨世纪学科带头人培养计划资助项目(98BR007)~~

摘　　要：目的探讨在有无慢性乙型肝炎的不同背景下p53基因第72密码子多态性(R72P)与中国人肝细胞癌(hepatocellular carcinoma,HCC)遗传易感性的关系.方法采用聚合酶链反应-限制性片段长度多态方法,检测469例HCC(HBsAg阴性110例、HBsAg阳性359例)与567名对照(HBsAg阴性430例、HBsAg阳性137例)的p53 R72P基因型分布及差异.结果全样本以及HBsAg阳性样本的HCC与对照间的基因型分布差异均无统计学意义.但在HBsAg阴性人群中,72P是HCC发生的危险因素(OR=1.69,95%CI=1.25～2.27).与R/R基因型相比,R/P的HCC风险增加至1.73倍(95%CI=0.93～3.11),P/P的HCC风险显著增加至3.29倍(95%CI=1.58～6.86).携带72P的男性个体、HCC家族史阳性个体的HCC风险分别进一步增加至9.39倍(95%CI=3.08～28.62)和11.14倍(95%CI=1.62～76.67).结论 p53 72P增加HBsAg阴性中国人的HCC风险,并与男性、HCC家族史在增加HCC风险中有协同作用.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 lergth 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： 1.2.5-2.27） 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. Conclusion 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.

关 键 词：肝细胞癌 P53基因 乙型肝炎 单核苷酸多态性 遗传易感性 

分 类 号：R735.7[医药卫生—肿瘤]