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p53基因密码子72 Arg/Pro多态性与肝细胞癌风险之间的关联。

Association between the p53 codon 72 Arg/Pro polymorphism and hepatocellular carcinoma risk.

作者信息

Lv Long, Wang Ping, Zhou Xiaoqing, Sun Beicheng

机构信息

Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.

出版信息

Tumour Biol. 2013 Jun;34(3):1451-9. doi: 10.1007/s13277-013-0649-7. Epub 2013 Apr 6.

Abstract

Previous studies regarding the association of p53 codon 72 Arg/Pro polymorphism with hepatocellular carcinoma (HCC) risk have provided conflicting and inconclusive findings. Thus, a meta-analysis of all currently available publications was performed to address this issue. Eleven individual case-control studies involving a total of 2,718 cases and 3,752 controls were identified after a systematic search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association of p53 codon 72 Arg/Pro polymorphism with HCC risk was estimated by the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI). Subgroup analyses stratified by ethnicity, source of controls, gender, hepatitis virus infection status, and family history of HCC were also conducted to assess the association. Overall, significantly increased risk of HCC was identified among carriers of the homozygous genotype ProPro (ORProPro vs. ArgArg=1.38 (95 % CI, 1.03-1.85), P OR=0.033; ORProPro vs. ArgArg + ArgPro =1.28 (95 % CI, 1.03-1.59), P OR=0.026). In subgroup analysis by ethnicity, the pooled results suggested that the p53 codon 72 Arg/Pro polymorphism was associated with an increased risk of HCC in Asians and Caucasians (for Asians, ORProPro vs. ArgArg + ArgPro=1.17 (95 % CI, 1.02-1.34), P OR=0.025; for Caucasians, ORProPro vs. ArgArg = 1.65 (95 % CI, 1.07-2.56), P OR=0.025; ORProPro vs. ArgArg + ArgPro=1.74 (95 % CI, 1.14-2.66), P OR=0.010). Subgroup analyses by source of controls and hepatitis virus infection status further demonstrated the significant association, whereas stratification factors involving gender and family history of HCC did not modify the association between p53 codon 72 Arg/Pro polymorphism and HCC risk. This meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism may play a critical role in the development of HCC, and gender and family history of HCC may not modulate the effect of p53 codon 72 Arg/Pro in HCC risk.

摘要

先前关于p53密码子72位精氨酸/脯氨酸多态性与肝细胞癌(HCC)风险关联的研究结果相互矛盾且尚无定论。因此,我们进行了一项对所有现有出版物的荟萃分析来解决这一问题。在对PubMed、Embase、科学网和万方数据库进行系统检索后,我们确定了11项个体病例对照研究,共涉及2718例病例和3752例对照。通过合并比值比(OR)及其相应的95%置信区间(95%CI)来估计p53密码子72位精氨酸/脯氨酸多态性与HCC风险关联的强度。我们还进行了按种族、对照来源、性别、肝炎病毒感染状况和HCC家族史分层的亚组分析,以评估这种关联。总体而言,在纯合子基因型ProPro携带者中发现HCC风险显著增加(ProPro与ArgArg相比,OR = 1.38(95%CI,1.03 - 1.85),P OR = 0.033;ProPro与ArgArg + ArgPro相比,OR = 1.28(95%CI,1.03 - 1.59),P OR = 0.026)。在按种族进行的亚组分析中,汇总结果表明,p53密码子72位精氨酸/脯氨酸多态性与亚洲人和高加索人中HCC风险增加相关(对于亚洲人,ProPro与ArgArg + ArgPro相比,OR = 1.17(95%CI,1.02 - 1.34),P OR = 0.025;对于高加索人,ProPro与ArgArg相比,OR = 1.65(95%CI,1.07 - 2.56),P OR = 0.025;ProPro与ArgArg + ArgPro相比,OR = 1.74(95%CI,1.14 - 2.66),P OR = 0.010)。按对照来源和肝炎病毒感染状况进行的亚组分析进一步证明了这种显著关联,而涉及性别和HCC家族史的分层因素并未改变p53密码子72位精氨酸/脯氨酸多态性与HCC风险之间的关联。这项荟萃分析表明,p53密码子72位精氨酸/脯氨酸多态性可能在HCC的发生发展中起关键作用,并且HCC的性别和家族史可能不会调节p53密码子72位精氨酸/脯氨酸对HCC风险的影响。

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