p53Arg72Pro多态性与细胞周期调控蛋白在HPV相关子宫颈鳞癌中的表达及意义

目的探讨p53Arg型和p53Pro型蛋白功能失活与细胞周期调控异常在HPV相关子宫颈鳞癌发生机制中的作用。方法应用免疫组织化学方法检测p53、CyclinD1、Cdk4、Rb磷酸化及Ki-67蛋白表达（PI）。结果在HPV阳性p53蛋白阴性的子宫颈鳞癌组中CyclinD1、Cdk4蛋白表达、Rb蛋白磷酸化率及PI值均明显高于子宫颈对照组（χ2=16.878,P〈0.01;χ2=21.120,P〈0.01;χ2=40.36,P〈0.01;t=30.53,P〈0.01）。CyclinD1与Cdk4蛋白表达、Rb磷酸化率均呈正相关（P〈0.01）,Rb高磷酸化组中的PI值高于低磷酸化组（P〈0.05）。p53Pro型子宫颈鳞癌组中CyclinD1蛋白表达和PI值均高于p53Arg型组和p53Pro/Arg型组（P〈0.05）。结论 HPV阳性的子宫颈鳞癌组中部分p53蛋白表达阴性,提示该部分p53蛋白被E6蛋白降解。在p53阴性的子宫颈鳞癌组织中PI值增高与CyclinD1-Cdk4-Rb磷酸化途径有关。p53Pro型组比p53Arg型组蛋白可能具有较强的细胞周期阻滞功能。     

p53 codon72多态性与HPV相关宫颈癌易患性的关系

高危型人乳头瘤病毒(humanpapillomavirus，HPV)感染是重要的宫颈癌致病因素。Storey等研究认为p53第4外显子72密码为精氨酸(Arg)纯合子的个体比脯氨酸(Pro)纯合子个体更易于发生HPV相关宫颈癌，但对此研究结果存在广泛争议。研究人群选择、标本取材、实验设计等不同是导致研究结果差异的原因。     

P53基因CD72Arg／Pro多态性与贲门腺癌生物学行为的研究

目的 探讨P53基因CD72 Arg／Pro多态性与中国汉族人贲门腺癌生物学行为的关系。方法 应用PCR—RFLP法对67例贲门腺癌患者和138名正常对照组人群P53基因CD72Arg／Pro多态性进行检测。结果 病例组P53基因Pro等位基因频率(0．672)和Pro／Pro基因型频率(47．8％)都显著高于正常对照组(0．413和13．0％)(P＜0．01)；携带Pro／Pro基因型者患贲门腺癌的风险比携带Arg／Arg基因型者显著升高，OR为8．30，95％CI：3．49—19．77(P＜0．01)。P53基因型分布和贲门腺癌的病理分化程度存在相关性(P＜0．01)。Pro／Pro基因型频率分布由高到低依次为：低分化组(69．6％)＞中分化组(42．3％)＞高分化组(27．8％)。有淋巴结转移的患者Pro／Pro基因型频率(63.3％)高于无淋巴结转移的患者(35．1％)(P＜0．05)。结论 P53基因Pro／Pro基因型是贲门腺癌的遗传易患因素，携带Pro／Pro基因型的贲门腺癌患者肿瘤恶性程度高、预后较差。     

p53基因第72位密码子多态性与HPV相关宫颈癌

流行病学研究显示，感染人乳头状瘤病毒(HPV)后，细胞内P53蛋白失活在宫颈癌发生中起关键作用。近年来国外关于p53基因第72位密码子的多态性与HPV相关宫颈癌发生的遗传易感性研究众多，但结果不尽一致。现主要综述该位点多态性在宫颈癌发生机制中的研究进展。     

p53 codon 72多态性与宫颈癌发生机制的研究

宫颈癌是女性常见的恶性肿瘤，严重影响妇女的生活质量。人乳头状瘤病毒感染是宫颈癌的主要致病因素，近几年的研究发现p53 codon 72多态性与宫颈癌的发生发展密切相关。现主要综述该位点多态性在宫颈癌发生机制中的研究进展。     

p53 codon 72多态性与宫颈癌发生机制的研究

宫颈癌是女性常见的恶性肿瘤,严重影响妇女的生活质量。人乳头状瘤病毒感染是宫颈癌的主要致病因素,近几年的研究发现p53 codon 72多态性与宫颈癌的发生发展密切相关。现主要综述该位点多态性在宫颈癌发生机制中的研究进展。     

HPV16 E6与p53 Arg72Pro基因的多态性

 目的探讨HPV16 E6对p53 Arg72Pro不同基因型的p53蛋白及其功能相关蛋白表达的影响,为研究宫颈癌的致癌机制提供理论依据。方法用脂质体法将真核表达载体pcDNA3.1/myc-His(-)A-HPV16 E6转染p53Arg和p53Pro细胞,通过免疫细胞化学方法对转染前后两种细胞内p53、p21、Bax、Ki-67蛋白进行检测。结果转染后两种细胞内p53、Bax、Ki-67蛋白的表达均受到影响,但p21蛋白变化不大。结论两种细胞内p53蛋白均可被降解,被降解后两者抑制细胞增殖能力和诱导细胞凋亡能力降低的程度不同,通过不同机制导致宫颈癌的发生。     

p53基因第72位密码子多态性与HPV相关宫颈癌

流行病学研究显示,感染人乳头状瘤病毒(HPV)后,细胞内P53蛋白失活在宫颈癌发生中起关键作用.近年来国外关于p53基因第72位密码子的多态性与HPV相关宫颈癌发生的遗传易感性研究众多,但结果不尽一致.现主要综述该位点多态性在宫颈癌发生机制中的研究进展.     

P21^WAF1/CIP1、BaX蛋白在维吾尔族宫颈癌p53Arg72Pro不同基因型中的表达研究

目的初步探讨p53Arg72Pro不同基因型的生物学功能以及在新疆维吾尔族宫颈癌发生机制中的相关作用。方法采用免疫组化的方法检测110例维吾尔族宫颈癌和45例维吾尔族正常宫颈组织中p53基因第四外显子第72位密码子Arg／Pro（p53Arg72Pro）三种基因型Arg／Arg、Pro／Arg、Pro／Pro型中P21^WAF1/CIP1、Bax蛋白的表达。结果在维吾尔族宫颈癌组织中P21^WAF1/CIP1、Bax蛋白的阳性表达率均高于正常宫颈组织，其表达差异有统计学意义（P〈0．05），同时在p53Arg72Pro三种基因型中Pro／Pro型的Bax蛋白阳性高表达率最高66．67％（10／15），其表达差异有统计学意义（P〈0．05）。而P21^WAF1/CIP1蛋白阳性表达率在Arg／Arg型中最高58．5％（24／41），但其差异并无统计学意义（P〉0．05）。结论p53Arg72Pro三种基因型在诱导细胞凋亡、转录激活以及调节细胞周期方面可能存在差异，p53Arg72Pro多态性可能通过不同的机制引起宫颈癌的发生。     

p53codon72多态性在乳腺癌发生发展中的作用

乳腺癌仍是女性发病率和死亡率最高的肿瘤之一,约占全世界女性肿瘤的1/3。其发生率因种族和地理环境而异,其中欧美国家为高发地区,亚洲发病率则明显降低。乳腺癌发病率近年来呈明显上升趋势,但其确切的发病机制尚未阐明。大约50%     

Association Between TP53 Arg72Pro Polymorphism and Hepatocellular Carcinoma Risk: A Meta-analysis

Background: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellularcarcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of theassociation by meta-analysis. Methods: We searched PubMed and Wangfang databases for published studieson the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR)with its 95% confidence intervals (95% CI) for assessment. Results: 10 studies with a total of 2,026 cases and2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism wasnot associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Proversus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProProversus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association betweenthe TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidenceof publication bias was observed. Conclusion: Meta-analyses of available data suggest an obvious associationbetween the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism mayhave a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.     

Polymorphisms of p53 Arg72Pro, p73 G4C14-to-A4T14 at exon 2 and p21 Ser31Arg and the risk of non-Hodgkin's lymphoma in Japanese

We hypothesized that the polymorphisms in the two p53 family genes (p53 Arg72Pro and p73 G4C14-to-A4T14 at exon 2 (G4A)) and p21 Ser31Arg polymorphism might modulate the risk of non-Hodgkin's lymphoma, and conducted a hospital-based prevalent case - control study at Aichi Cancer Center Hospital to clarify the association. Risk estimation for each genotype by the unconditional logistic model demonstrated the possible association between the p53 Pro72 allele and the risk of non-Hodgkin's lymphoma in Japanese population (OR = 1.59; 95% CI, 0.99 - 2.57, P = 0.057), although no other significant association was observed. The analyses of statistical interactions between these three polymorphisms (p73 G4A, p53 Arg72Pro and p21 Ser31Arg polymorphisms) revealed the marginally significant OR for interaction between p53 Arg72Pro and p73 G4A polymorphisms (OR = 2.54; 95% CI, 0.97 - 6.62, P = 0.057). When those without p53 Pro72 and p73 A4T14 alleles were defined as a reference, those with p53 Pro72 and p73 A4T14 alleles demonstrated a significantly higher OR (2.08; 95% CI, 1.11 - 3.90, P = 0.023). Further examination with a sufficiently larger population and other ethnicities are required to confirm our findings.     

p53 Arg72Pro polymorphism,adiposity status,and cancer risk: Two case‐cohorts within a Japanese prospective study

The tumor suppressor protein, p53, is a critical molecule involved in cancer development. However, the association between p53 Arg72Pro polymorphism and cancer risk remains unclear, possibly due to the pro‐tumor potential of p53 under metabolic stress. Here, we hypothesized that the p53 Arg72Pro polymorphism plays different roles during tumorigenesis by adiposity status. We measured baseline body mass index (BMI) and p53 Arg72Pro polymorphism for two case‐cohorts, which included 4264 cancers with up to 20 years of follow‐up. Multivariable‐adjusted hazard ratios (HRs) and confidence intervals (CIs) were estimated using weighted Cox proportional‐hazards method. Without consideration of adiposity status, p53 Arg72Pro polymorphism was not associated with cancer risk. However, proline (Pro) homozygous genotype conferred an increased cancer risk for individuals with a BMI <25 kg/m² (HR [95% CI]: 1.12 [1.00–1.26] for total cancer and 1.19 [1.02–1.38] for obesity‐related cancer), but not for those with a BMI ≥ 25 kg/m². The heterogeneous effect of p53 Arg72Pro polymorphism on cancer risk according to adiposity status was indicated (p _{heterogeneity}: 0.07 for total cancer and 0.03 for obesity‐related cancer). Furthermore, the association between overweight and cancer risk was only observed in arginine (Arg) carriers, but not in Pro homozygous carriers (p _{heterogeneity}: 0.07 for total cancer and 0.02 for obesity‐related cancer). Pro homozygous carriers were more likely to be predisposed to cancer than Arg carriers with normal‐weight conditions. In addition, overweight was related to a higher cancer risk in Arg carriers than Pro homozygous carriers. Our findings may suggest the adiposity‐dependent dual effects of p53 Arg72Pro polymorphism during tumorigenesis.     

TP53 Gene Pro72Arg (rs1042522) Single Nucleotide Polymorphism as Not a Risk Factor for Colorectal Cancer in the Iranian Azari Population

Background: The p53 protein participates critically in several cellular functions such as cell growth and DNA repair. Polymorphisms in the TP53 locus have repeatedly been implicated in the pathogenesis of cancers all over the world. Over 200 single nucleotide polymorphisms (SNPs) have been characterized, but one well-known example at at codon 72, Pro72Arg (rs1042522), has the displayed inconsistent results with regard to cancer risk. Herein, we aimed to evaluate whether Pro72Arg (rs1042522) single nucleotide polymorphism (SNP) in TP53 gene might be associated with risk of colorectal cancer in the Iranian Azari population. Methods: Blood samples were taken from 100 healthy controls and 100 colorectal cancer patients with Iranian-Azeri ethnicity. Genotyping was performed with Tetra-ARMS PCR. Results: The alleles of the TP53 gene Pro72Arg SNP did not significantly differ in prevalence between patients and controls (P>0.05). Additionally, genotypes of Pro72Arg SNP were not significantly associated with colorectal cancer risk in the studied population. Conclusions: Pro72Arg SNP of TP53 gene may not be involved in the disease pathogenesis in Iranian Azari patients with colorectal cancer.     

TP53 Arg72Pro polymorphism and lung cancer risk: A meta‐analysis

No clear consensus has been reached on the TP53 Arg72Pro polymorphism (G12139C) and lung cancer risk. Thus, a meta‐analysis was conducted to summarize the possible association. There was no statistical association between 12139C (Pro allele) and lung cancer risk in Caucasians compared with 12139G allele. However, the association was observed in all subjects (9,387 patients and 9,922 controls, p = 0.04, OR = 1.08, 95% CI 1.00–1.17), as well as in Asians (p = 0.0004, OR = 1.14, 95% CI 1.06–1.22). The association was also found in Asians under recessive genetic model (p < 0.00001, OR = 1.37, 95% CI 1.20–1.57) and homozygote comparison (CC vs. GG) (p < 0.0001, OR = 1.34, 95% CI 1.16–1.56). 12139C allele might increase the lung adenocarcinoma risk compared with 12139G allele (p = 0.01, OR = 1.11, 95% CI 1.02–1.21), and the effect was also found under recessive genetic model (p = 0.003, OR = 1.28, 95% CI 1.09–1.50) and homozygote comparison (CC vs. GG) (p = 0.007, OR = 1.28, 95% CI 1.07–1.52). There was an elevated association between the 12139C and the stage I lung cancer under dominant genetic model (p = 0.04, OR = 1.48, 95% CI 1.02–2.16), but no association was observed in other stages. No association of smoking was found between 12139C allele and lung cancer under recessive genetic model. Our result indicated that 12139C might increase the risk of lung cancer under recessive genetic model in adenocarcinoma, in Asians, and in lung cancer stage I. More studies stratified for lung cancer stage‐genotyping interaction should be performed to clarify the role of TP53 Arg72Pro polymorphism in the development of lung cancer. © 2009 UICC     

Pro variant of TP53 Arg72Pro contributes to gastric cancer risk in Asians: evidence from a meta-analysis

Background: Previous studies investigating the association between TP53 Arg72Pro polymorphism and gastric cancer (GC) risk in Asian population have reported controversial results. Thus, a meta-analysis was performed. Methods: A comprehensive literature search was conducted and 17 case-control studies were finally included, involving a total of 5,990 GC cases and 6,812 controls. Subgroup analyses were performed by the sample size. Results: Meta-analysis of all 17 studies showed variant genotypes of TP53 Arg72Pro to be associated with an elevated GC risk in three genetic comparison models (ORPro vs. Arg =1.13, 95%CI 1.03-1.25, POR=0.01; ORHomozygote comparison model =1.33, 95%CI 1.07-1.64, POR=0.009; ORDominant genetic model =1.13, 95%CI 1.05-1.22, POR=0.002). Besides, a more obvious association was observed after the heterogeneity was decreased (all P values less than 0.001). This association was further identified by both subgroup and sensitivity analyses. Conclusions: This meta-analysis suggests the Pro variant of TP53 Arg72Pro contributes to gastric cancer risk in Asians.     

四川地区P53 Codon 72多态性与宫颈癌关系的初步研究

目的 探讨抑癌基因P53 Codon 72多态性与HPV有关的宫颈癌的关系。 方法 应用聚合酶链反应法分别对30例卵巢浆液性囊腺癌、50例宫颈鳞状细胞癌和30例正常妇女的P53 Codon 72多态性进行检测。 结果 P53 Arg纯合子、P53 Arg/P53 Pro杂合子和P53Pro纯合子正常妇女对照组分别为33.3％、60％和6.7％;而在卵巢癌组分别为40％、53.3％和6.7％;在宫颈癌组分别为80％、14％和6％。上述人群中,宫颈癌P53 Arg纯合子明显高于卵巢癌组和正常妇女对照组(P<0.05)。 结论 p53 Arg纯合子可作为与HPV感染有关的宫颈癌的危险因素。     

p53 Codon 72 polymorphism and the risk of esophageal squamous cell carcinoma

The polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous malignant tumors, particularly carcinomas associated with human papillomavirus (HPV) infection. However, the results remain controversial. To address a potential correlation between the p53 genotypes and the risk of esophageal squamous cell carcinoma (ESCC), we investigated the p53 codon 72 polymorphism in 435 patients with ESCC and 550 cancer-free subjects from the same geographical region. p53 Arg/Arg genotype was significantly increased in ESCC cases compared with control subjects (85.7 vs. 49.6%, P < 0.001), resulting in an elevated ESCC risk (OR = 6.48, 95% CI = 4.65-9.03). In addition, among p53 Arg/Arg carriers, HPV infection, smoking, and drinking might further increase the risk of ESCC development.     

云南省住院肺癌患者HPV16/18感染及p53codon72多态性检测分析

目的分析云南省住院肺癌患者HPV16/18感染以及p53codon72位点基因多态性。方法收集2012-12-01-2013-09-30昆明医科大学第一附属医院胸外科手术切除的63例肺癌组织和24例肺良性病变组织,采用聚合酶链反应(polymerase chain reaction,PCR)分别检测肺癌组织和肺良性病变组织中HPV16/18以及p53codon72的DNA。结果肺癌组织的HPV16/18阳性检出率为47.63%,显著高于肺良性病变组织8.33%,χ2=11.535,P=0.001。HPV16/18感染仅与肿瘤分化程度相关,u=6.853,P=0.021;与性别(χ2=0.640,P=0.424)、年龄(χ2=0.049,P=0.825)、吸烟史(χ2=0.965,P=0.326)、肿瘤类型(u=0.593,P=0.764)、肿瘤分期(u=0.885,P=0.625)和转移情况(χ2=0.688,P=0.407)无关。p53condon72Arg/Arg、Pro/Pro和Arg/Pro在肺癌组织的分布频率分别为28.57%、53.97%和17.46%,肺良性病变组织的分布频率分别为29.17%、29.17%和41.67%,差异有统计学意义,χ2=6.489,P=0.038。p53condon72Arg/Arg、Pro/Pro和Arg/Pro在HPV阳性肺癌组织的分布频率分别为16.67%、70.00%和13.33%,在HPV阴性肺癌组织的分布频率分别为39.39%、39.39%和21.21%,差异有统计学意义,χ2=6.127,P=0.046。结论云南省住院肺癌患者中高危HPV16/18型呈高感染,p53Pro/Pro基因分型高表达,两者均为该地区肺癌发生的高危因素。