AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53Arg72Pro polymorphism and susceptibility to hepatoc...AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population.METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs)from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC.RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P = 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P = 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant.CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC.展开更多
目的探讨人群TP53基因Arg72Pro(rs1042522)位点单核苷酸多态性与甲状腺癌的相关性。方法检索PubMed、Embase、Web of Science数据库,搜索TP53基因Arg72Pro位点多态性与甲状腺癌发病风险相关的文献,筛选出符合要求的风险关联性研究,使用S...目的探讨人群TP53基因Arg72Pro(rs1042522)位点单核苷酸多态性与甲状腺癌的相关性。方法检索PubMed、Embase、Web of Science数据库,搜索TP53基因Arg72Pro位点多态性与甲状腺癌发病风险相关的文献,筛选出符合要求的风险关联性研究,使用Stata 14.0软件进行meta分析,并进行敏感性分析、亚组分析及发表偏倚评价。采用比值比(OR)及其相应的95%CI作为效应量来评价TP53基因Arg72Pro位点单核苷酸多态性与甲状腺癌发病风险的关系。结果共计13篇文献纳入meta分析,甲状腺癌2 112例,对照4 000例。Meta分析的总体结果显示,TP53基因Arg72Pro位点的突变纯合子(Pro/Pro)基因型能够增加总人群罹患甲状腺癌的风险(隐性模型OR=1.78,95% CI 1.24~2.56,P=0.002),在甲状腺癌患者中该位点Pro突变比例较高(等位基因模型OR=1.35,95% CI 1.12~1.63,P=0.002)。亚组分析显示,该位点的突变纯合子(Pro/Pro)基因型能够增加亚洲人罹患甲状腺癌的风险,但与欧洲人及南美洲人罹患甲状腺癌无关;该位点的突变纯合子(Pro/Pro)基因型能够增加总人群罹患甲状腺乳头状癌的风险,但与总人群罹患甲状腺髓样癌无关。结论TP53基因Arg72Pro位点突变与甲状腺癌的发生相关,尤其在亚洲人群中,该位点的突变纯合子基因型Pro/Pro可能为甲状腺癌发生的危险因素。展开更多
The TP53 gene is well known to be the most frequently mutated gene in human cancer.In addition to mutations,there are > 20 different coding region single-nucleotide polymorphisms (SNPs) in the TP53 gene,as well as ...The TP53 gene is well known to be the most frequently mutated gene in human cancer.In addition to mutations,there are > 20 different coding region single-nucleotide polymorphisms (SNPs) in the TP53 gene,as well as SNPs in MDM2,the negative regulator of p53.Several of these SNPs are known to alter p53 pathway function.This makes p53 rather unique among cancer-critical genes,e.g.the coding regions of other cancer-critical genes like Ha-Ras,RB,and PI3KCA do not have non-synonymous coding region SNPs that alter their function in cancer.The next frontier in p53 biology will consist of probing which of these coding region SNPs are moderately or strongly pathogenic and whether they influence cancer risk and the efficacy of cancer therapy.The challenge after that will consist of determining whether we can tailor chemotherapy to correct the defects for each ofthese variants.Here we review the SNPs in TP53 and MDM2 that show the most significant impact on cancer and other diseases.We also propose avenues for how this information can be used to better inform personalized medicine approaches to cancer and other diseases.展开更多
基金Supported by the National Natural Science Foundation of China,No. 30370645, by the Hundred Leading Scientists Program of the Public Health Sector of Shanghai, No, 98BR007
文摘AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population.METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs)from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC.RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P = 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P = 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant.CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC.
文摘目的探讨人群TP53基因Arg72Pro(rs1042522)位点单核苷酸多态性与甲状腺癌的相关性。方法检索PubMed、Embase、Web of Science数据库,搜索TP53基因Arg72Pro位点多态性与甲状腺癌发病风险相关的文献,筛选出符合要求的风险关联性研究,使用Stata 14.0软件进行meta分析,并进行敏感性分析、亚组分析及发表偏倚评价。采用比值比(OR)及其相应的95%CI作为效应量来评价TP53基因Arg72Pro位点单核苷酸多态性与甲状腺癌发病风险的关系。结果共计13篇文献纳入meta分析,甲状腺癌2 112例,对照4 000例。Meta分析的总体结果显示,TP53基因Arg72Pro位点的突变纯合子(Pro/Pro)基因型能够增加总人群罹患甲状腺癌的风险(隐性模型OR=1.78,95% CI 1.24~2.56,P=0.002),在甲状腺癌患者中该位点Pro突变比例较高(等位基因模型OR=1.35,95% CI 1.12~1.63,P=0.002)。亚组分析显示,该位点的突变纯合子(Pro/Pro)基因型能够增加亚洲人罹患甲状腺癌的风险,但与欧洲人及南美洲人罹患甲状腺癌无关;该位点的突变纯合子(Pro/Pro)基因型能够增加总人群罹患甲状腺乳头状癌的风险,但与总人群罹患甲状腺髓样癌无关。结论TP53基因Arg72Pro位点突变与甲状腺癌的发生相关,尤其在亚洲人群中,该位点的突变纯合子基因型Pro/Pro可能为甲状腺癌发生的危险因素。
文摘The TP53 gene is well known to be the most frequently mutated gene in human cancer.In addition to mutations,there are > 20 different coding region single-nucleotide polymorphisms (SNPs) in the TP53 gene,as well as SNPs in MDM2,the negative regulator of p53.Several of these SNPs are known to alter p53 pathway function.This makes p53 rather unique among cancer-critical genes,e.g.the coding regions of other cancer-critical genes like Ha-Ras,RB,and PI3KCA do not have non-synonymous coding region SNPs that alter their function in cancer.The next frontier in p53 biology will consist of probing which of these coding region SNPs are moderately or strongly pathogenic and whether they influence cancer risk and the efficacy of cancer therapy.The challenge after that will consist of determining whether we can tailor chemotherapy to correct the defects for each ofthese variants.Here we review the SNPs in TP53 and MDM2 that show the most significant impact on cancer and other diseases.We also propose avenues for how this information can be used to better inform personalized medicine approaches to cancer and other diseases.
