p53基因72位密码子多态性与高脂血症的相关性

目的 探讨p53基因72位密码子多态性与高脂血症的相关性。方法 采用PCR-RFLP技术和PCR方法检测高脂血症组202例（均为胆固醇和低密度脂蛋白水平升高）和正常对照组194例p53基因72位密码子多态性的分布情况。结果 p53基因72位密码子多态性位点基因型为ArgArg/ArgPro/ProPro,高脂血症组三种基因型频率分别为39.1%、45.0%和15.8%,正常对照组三种基因型频率分别为28.4%、55.7%和16.0%,两组差异无显著性（P>0.05）;两组中女性的3种基因型频率分别为42.8%、42.1%、15.1%和27.3%、58.0%、14.7%,差异有统计学意义（P0.012）;男性中三种基因型分布差异无显著性（P>0.05）。等位基因频率在两组中及男性、女性中的分布差异均没有统计学意义。结论 p53基因72位密码子多态性与高脂血症存在相关性,携带Arg/Arg基因型的女性高脂血症发病风险增高。基因型Arg/Arg可能是高胆固醇、高低密度脂蛋白血症发生的一个危险因素。     

P53Arg72Pro多态性及H pylori感染与胃癌高发区甘肃河西地区胃癌的关系

目的:检测H pylori在甘肃河西地区健康人群与胃癌患者中的感染,并探讨P53Arg72Pro基因多态性以及H pylori感染与胃癌高发区甘肃河西地区胃癌发生的关系.方法:采用PCR-TaqMan探针法检测甘肃河西地区健康人群和胃癌患者P53Arg72Pro的基因多态性,用Warhin-starry染色法检测本研究对象的H pylori感染率.结果:H pylori感染率在胃癌组和对照组分别为68.6%,50.4%,H pylori感染率在两组间具有显著差异(OR=2.147,95%CI:1.302-3.541);P53Arg72Pro分为Arg/Arg,Arg/Pro,Pro/Pro3 种基因型,其频率在胃癌患者中分别为15.7%,60.0%,24.3%;在健康人群中分别为25.6%,54.4%,20.0%.与Arg/Arg基因型相比,Arg/Pro或Pro/Pro单独频率在2组间差异无统计学意义,但P53Pro等位基因(Arg/Pro+Pro/Pro)携带者在胃癌者和对照组间差异有统计学意义(OR=1.846;95%CI:1.006-3.387).分层分析提示H pylori阳性感染者或吸烟人群,若其同时携带有P53Pro等位基因,他们患胃癌的风险明显增加.结论:P53Arg72Pro位点基因多态性与我国胃癌高发区甘肃河西地区胃癌发病的风险相关,P53Pro等位基因与H pylori感染或吸烟因素有一定的协同作用.     

胃肠病学和肝病学杂志2005年总目次

食管吞咽困难……………………………………………………………………………李玉龙段芳龄马军160Barrett’s食管(BE)研究进展吴诚施斌朱木梁………………………………………………………215河南安阳地区p53基因第72密码子多态性与HPV相关食管癌的研究……何保昌段广才张卫东等374食管鳞状细胞癌及不典型增生组织中hMLH1基因蛋白表达的研究………吕新全李惠翔高冬玲等377食管鳞状细胞癌中VEGF与TIMP-2、MVD、树突状细胞的关系及对浸润转移的影响李惠翔杨吉龙高冬玲等380………………………………………………………………………………     

肝细胞癌肿瘤抑制基因p53过度表达及点突变的研究

目的检测重庆地区肝细胞癌 p53突变发生率,并进一步探讨 p53突变与肝细胞癌临床病理及相关危险因素的关系.方法应用一种敏感的 ARF 免疫组化和 PCR、银染 PCR-SSCP 方法检测本地区38例肝细胞癌(HCC)组织中肿瘤抑制基因p53的过度表达及点突变.结果 16例有P53蛋白过度表达(41.2%),7例有 p53基因249位密码子点突变(18.4%),2例249位密码子外第7外显子点突变.9例 p53基因有突变的肝癌中8例 P53蛋白阳性,两者符合率为88.9%.p53基因蛋白过度表达和点突变与 HCC 分化和转移有关.本组 HCC p53基因突变率与该地区黄曲霉素(AFB1)含量及乙型肝炎病毒(HBV)感染分布一致.结论该结果提示 p53基因突变与 AFB1和 HBV 等环境因素的协同作用有关,其中 AFB1主要与 p53基因249位密码子特异型突变有关,而 HBV 可能在散发型突变中发挥重要作用.     

原发性肝细胞癌患者 p53基因突变的特征和临床意义的研究

[摘要]　目的　 探讨p53基因突变在原发性肝细胞癌（hepatocellular carcinoma, HCC）患者中的特征和临床意义，并分析其对预后的影响。方法　选取我院2019年1月1日—2020年4月30日收治的慢性乙型肝炎肝硬化和HCC患者各120例，分别作为慢性乙型肝炎肝硬化组和HCC组。选取同期于我院行体检的120例健康体检者作为健康对照组。采用化学发光法检测HCC患者血清特异性肿瘤标志物甲胎蛋白异质体（alpha-fetoprotein L3, AFP-L3）、高尔基糖蛋白-73（golgi protein 73, GP73）、异常凝血酶原（des-γ-carboxy-prothrombin, DCP）水平。采用聚合酶链反应-限制性片段长度多态性方法检测3组p53第4外显子72位密码子（p53 Arg72Pro）基因型，分析不同组间p53 Arg72Pro基因型差异，并比较HCC组患者不同p53 Arg72Pro基因型间AFP-L3、GP73、DCP水平及HBV DNA阳性率和生存率差异。结果　HCC组携带Pro/Pro基因型患者比例为33.3%，高于慢性乙型肝炎肝硬化组的14.2%和健康对照组的13.3%，差异均具有统计学意义（P均＜0.05）。在HCC患者中，Pro/Pro型患者发病年龄明显小于Arg/Pro型和Arg/Arg型患者，而巴塞罗那分期为C/D期和伴有淋巴结转移的患者比例明显高于Arg/Pro型和Arg/Arg型患者， HBV DNA检测阳性率明显高于Arg/Arg型，血清特异性肿瘤标志物AFP-L3、GP73、DCP水平均明显高于Arg/Arg型和Arg/Pro型患者，差异均具有统计学意义（P均＜0.05）。Arg/Arg型HCC患者生存率为83.3%，高于Arg/Pro型和Pro/Pro型患者的63.3%，差异具有统计学意义（P＜0.05）。结论　p53 Arg72Pro基因突变与HCC的发生存在密切关联，且与多个HCC血清特异性肿瘤标志物密切相关，可能是加速患者癌变进展过程中的关键调节因子。     

广西巴马壮族长寿老人p53基因的多态性研究

目的探讨抑癌基因p53第4外显子第72位密码子（codon72）与人类长寿的关系。方法应用PCR—RFLP技术对巴马156例（年龄90-105岁，平均93．2岁，长寿组）健康壮族长寿老人和142例健康壮族成年人（年龄20-72岁，平均34．8岁，对照组）的p53基因进行分型，了解这些基因的多态性，分析该基因（型）频率在长寿组和对照组之间的差异及其与长寿的关系。结果长寿组p53codon72片段的野生型（G／G）频率明显高于对照组（53％：29％，P〈0．05）。结论p53基因的多态性与人类长寿有着较为密切的联系，其具体作用机制有待进一步研究。     

肝细胞癌p53基因249密码子热点突变的研究

目的 研究肝细胞癌(HCC)中p53基因249密码子(p53 E7 cd249)点突变情况。方法 用PCR法及HAEⅢ限制性片段长度多态性分析(HAEⅢ/RFLP)检测河南豫东地区38例HCC石蜡包埋组织及2例肝细胞癌株中p53 E7cd249点突变情况,DNA测序证实。选取广西桂西南地区的10例HCC作对照。结果 来自河南豫东地区的HCC p53 E7 cd249点突变率为10.5％(4/38),对照组广西桂西南地区的HCC p53 E7 cd249点突变为40％(4/10),二者相比具有显著性差异(P<0.05)。2例肝细胞癌株中均未发现HCC p53 E7 cd249点突变。结论 河南豫东地区HCC中p53基因E7 cd249点突变为非高发事件;p53 E7 cd249点突变可能发生在肝细胞癌变的晚期。     

P53基因密码子72多态性与大肠癌易感性的Meta分析

目的探讨P53基因密码子72多态性与大肠癌风险的相关性。方法全面检索Pub Med、Medline、EMbase、CBM、CNKI、万方和维普等数据库。检索时间从建库至2014年2月,收集P53基因密码子72多态性与大肠癌易感性的病例对照研究。采用Rev Man 5.2软件计算合并效用量OR及其95%CI。结果共纳入25个研究,其中有6 753例患者,8 562例对照者。Meta分析发现,在各遗传模型中,隐性模型PP vs AP+AA中P53基因密码子72多态性与大肠癌发生风险有明显相关性,其余基因模型中P53基因密码子72多态性与大肠癌发生风险无明显相关性。结论在PP vs AP+AA遗传模型中,P53基因密码子72多态性与大肠癌风险性显著相关。     

汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌关系的研究

目的探讨汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌之间的关系。方法原发肝癌患者50例,肝炎肝硬化患者61例,健康献血人员92例。针对XRCC1基因的10号外显子设计引物,PCR产物利用MspⅠ限制性酶切进行基因分型,基因型分成XRCC1 399Arg/Arg,399Arg/Gln,399Gln/Gln三种,分析XRCC1多态性与肝癌之间的关系。结果原发肝癌患者中XRCC1 399Arg/Arg 32例(64.0%),Arg/Gln 14例(28.0%),Gln/Gln 4例(8.0%);肝炎肝硬化患者中Arg/Arg 30例(49.2%),Arg/Gln 23例(37.7%),Gln/Gln 8例(13.1%);健康人群Arg/Arg 46例(50.0%),Arg/Gln 41例(44.5%),Gln/Gln 5例(5.5%)。以健康人群为对照组,XRCC1399Gln基因(基因型Arg/Gln和Gln/Gln)并不增加患肝癌的风险性(OR=0.563,95%CI:0.277-1.141,P=0.109);以肝炎肝硬化为对照组,XRCC1 399Gln基因同样与患肝癌的易感性之间没有显著的相关性(OR=0.544,95%CI:0.253-1.170,P=0.118)。结论XRCC1基因密码子399位点的基因多态性与汉民族原发肝癌危险性无统计学相关关系。     

胃癌前疾病不同中医证型的p53、EGFR基因多态性研究

[目的]探讨胃癌前疾病不同中医证型与p53、EGFR基因多态性的相关性。[方法]招募85例胃癌前疾病患者及20名健康志愿者,采用等位基因专一性实时荧光PCR技术检测分析TP53:215C/G(R72P)、EGFR:1562G/A(R521K)的基因多态性。[结果]EGFR:1562AG基因型在脾胃虚弱证显著增高,和健康对照组比较有显著性差异;TP53:215C/G(R72P)基因型在各组的分布无显著性差异。[结论]不同胃癌前疾病中医证型p53、EGFR基因型分布不尽相同,提示不同中医证型和基因多态性有着相关性。     

p53polymorphism in human papillomavirus-associated Kazakh＇s esophageal cancer in Xinjiang, China

AIM: To investigate the relationship between p53 codon 72 polymorphism and human papillomavirus (HPV) type 16 infection in Kazakh‘s esophageal cancer (EC) in Xinjiang, China.METHODS: Encoding regions of p53codon 72 and HPV-16 E6 were amplified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction (PCR) methods using pairs of primary esophageal squamous cell carcinoma (SCC) tissue and corresponding normal mucosa, which were collected from 104 patients of Kazakh in Xinjiang, China. RESULTS: Only arginine allele was detected in 70.1% (39/55) of HPV-16-E6-positive cases but only in 40.8% (20/49) of HPV-16-E6-negative cases (P&lt;0.05; OR, 3.53; 95% CI, 1.57-7.98). In contrast, such a significant correlation between p53 polymorphism and HPV infection was not evident in corresponding normal mucosae. The allele frequency of Arg allele in cancer cases (0.68) was higher than that in normal mucosa samples (0.54) (P&lt;0.05; OR, 1.80; 95% CI, 1.21-2.69).CONCLUSION: p53 codon 72 Arg homozygous genotype is one of the high-risk genetic factors for HPV-associated SCC of Kazakh. Individuals carrying Arg allele compared to those with Pro allele have an increased risk for esophageal SCC.     

Infection of human papillomavirus type 18 and p53 codon 72 polymorphism in lung cancer patients from India

STUDY OBJECTIVES: Infection with specific high-risk HPV types 16 and 18 and polymorphism of p53 codon 72 has been strongly associated with the genesis of various neoplasms in humans, but such study in lung cancer is limited and the results are controversial. In India, the role of these two factors has been strongly implicated in cervical and other cancers, but the occurrence of HPV or p53 codon 72 polymorphism has not been examined in lung cancer, which is the most common cause of cancer-related death in India.Design and patients: A total of 40 tumor biopsy specimens from advanced lung cancer patients and blood samples from 40 matching control subjects were obtained for the analysis of high-risk HPV types 16 and 18 infection and p53 codon 72 polymorphism by polymerase chain reaction. RESULTS: Only HPV type 18 was detected in 5% (2 of 40 lung cancer patients), but no other HPV could be detected. A significantly increased frequency of Arg/Arg homozygotes was observed in patients with advanced lung cancer when compared to that of control subjects (p = 0.004; odds ratio, 5.13; 95% confidence interval, 1.59 to 17.26). However, no significant correlation could be made between p53 polymorphism and different clinical stages, except for advanced stage IV patients, who showed a higher proportion of Arg/Pro heterozygous genotype. CONCLUSIONS: HPV detected in a small proportion of lung cancer patients in India demonstrated an exclusive prevalence of HPV type 18, and there was a significantly higher frequency of p53 Arg/Arg genotype when compared to that of control subjects. Observation of a shorter duration of symptoms (< or = 4 months) in as many as 78% (seven of nine stage IV patients) with Arg/Pro genotype may be an indication that lung cancer patients with the heterozygous p53 genotype are more susceptible to early progression.     

Evaluation of p53 codon 72 polymorphism in adenocarcinomas of the colon and rectum in La Plata, Argentina

AIM: To evaluate the potential association between p53 codon 72 polymorphism and sporadic colorectal ad-enocarcinoma development, and human papillomavirus (HPV) infection. METHODS: One-hundred and nine controls and 53 patients with colon cancer from the city of La Plata, Argentina were analyzed. p53 codon 72 genotypes and HPV infection were identified using allele-specific polymerase chain reaction and nested polymerase chain reaction, respectively. RESULTS: The differences in the distribution of p53 codon 72 polymorphism between the cases and controls were statistically significant. The arginine allele had a prevalence of 0.65 in controls and 0.77 in cases. The corresponding odds ratio for the homozygous arginine genotype was 2.08 (95% CI, 1.06-4.05; P<0.05). Lack of association was found between p53 polymorphism and HPV infection in the set of adenocarcinomas. CONCLUSION: The findings of the present study indicate that p53 codon 72 arginine homozygous genotype may represent a genetic predisposing factor for colon cancer development. However, further studies are needed in order to elucidate the role of p53 codon 72 polymorphism in colorectal cancer.     

Polymorphism at codon 72 of p53, human papillomavirus,and cervical cancer in South India

PURPOSE: It has been suggested that host genetic factors play a role in human papillomavirus (HPV)-associated tumorigenesis, although the issue continues to be a focus of much debate. Previous studies have reported that a common polymorphism of the wild type p53 gene at codon 72 of exon 4 (Arg/Arg) is associated with a sevenfold increased risk of HPV-associated cancer compared to Arg/Pro and Pro/Pro polymorphisms. In vitro studies also suggested that the Arg/Arg polymorphism was much more susceptible to HPV 16 E6-mediated degradation as compared to other allelic forms. Subsequent studies published since this initial report indicated geographical differences with respect to the role of Arg/Arg polymorphism in increasing the risk of HPV-associated cervical cancer. METHODS: In this study we analyzed leukocyte DNA from a total of 421 subjects for the Arg/Arg, Arg/Pro or Pro/Pro p53 polymorphisms at various stages of the cervical tumor progression spectrum, using allele-specific PCR. All subjects were from the Thiruvananthapuram District of South India. HPV genotyping was done for all subjects using either DNA extracted from cervical biopsies or exfoliated cervical cells. All subjects were grouped on the basis of both of cyto-pathology and HPV status. RESULTS: The distribution of p53 genotypes was not significantly different in all study groups (HPV positive vs HPV negative and cases vs controls comparisons). Homozygosity for Arg/Arg was not associated with increased risk for cervical cancer. CONCLUSION: We find no evidence for any association between homozygosity for p53 arginine with either cervical dysplasia, cervical carcinoma or HPV infection in the population from South India.     

Lack of correlation between p53 codon 72 polymorphism and anal cancer risk

AIM： To investigate the potential role of p53 codon. 72 polymorphism as a risk factor for development of anal cancer. METHODS： Thirty-two patients with invasive anal carcinoma and 103 healthy blood donors were included in the study, p53 codon 72 polymorphism was analyzed in blood samples through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS： The relative frequency of each allele was 0.60 for Arg and 0.40 for Pro in patients with anal cancer, and 0.61 for Arg and 0.39 for Pro in normal controls. No significant differences in distribution of the codon 72 genotypes between patients and controls were found. CONCLUSION： These results do not support a role for thep53 codon 72 polymorphism in anal carcinogenesis.     

Prognostic role of p53 codon 72 polymorphism in gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy

OBJECTIVE: The polymorphism of p53 codon 72 (Arg72Pro) has been suggested to play an important role in many cancers and may influence the response to chemotherapy. Our aim was to investigate the association of p53 Arg72Pro polymorphism with the clinical outcome of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy. METHODS: The p53 codon 72 genotype was determined in blood samples from 110 Chinese patients with gastric cancer treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy, using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. RESULTS: Kaplan-Meier survival analysis showed that gastric cancer patients with Pro/Pro genotype had shorter relapse-free survival (chi(2) = 10.632, P = 0.005) and overall survival (chi(2) = 7.104, P = 0.029) than patients with other genotypes. Cox multivariate analysis showed that Pro/Pro genotype was associated with statistically significant reduced relapse-free survival (adjusted OR = 3.049, 95% CI: 1.363-6.819, P = 0.007) and overall survival (adjusted OR = 2.581, 95% CI: 1.052-6.330, P = 0.038). CONCLUSION: These results suggested that p53 codon 72 polymorphism appears to be an independent prognostic factor in gastric cancer patients treated with 5-FU-based adjuvant chemotherapy.     

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case‐control study

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case‐control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real‐time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85–1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02–2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92–1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15–2.74) for EC overall. In never‐smokers and ever‐smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37–0.95) and 1.39 (95% CI = 1.00–1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case‐control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.     

A p53 genetic polymorphism of gastric cancer： Difference between early gastric cancer and advanced gastric cancer

INTRODUCTIONGastric cancer is one of the most common malignancies worldwide,although the overall incidence of gastric cancer has been decreasing over the past few decades.Chronic H pylori infection and dietary factors,such as those high in salt or nitrate…     

Arginine and proline alleles of the p53 gene are associated with different locations of gastric cancer

BACKGROUND/AIMS: Abnormal function of gene p53 is associated with the formation of various cancers including gastric cancer. Recently, p53 codon 72 polymorphism was extensively studied to determine the risk factors responsible for cancer formation using the concept of single nucleotide polymorphism. In this study, we evaluated the risk factors associated with p53 codon 72 polymorphism and gastric cancer carcinogenesis. METHODOLOGY: This study consisted of 51 patients and 59 control subjects. We then evaluated the patient's age, sex, smoking and alcohol consumption habits, tumor location, cell differentiation, lymph node involvement, distant metastasis and tumor stage. Finally the p53 gene codon 72 polymorphism was analyzed by polymerase chain reaction (PCR). The results of polymorphic genotype were stratified with the above risk factors and the associations were analyzed. RESULTS: There was no significant difference between the polymorphic genotypes and the two study groups. However, when the genotypes were further stratified with co-factors, the results revealed a significant association with tumor location. The proline homozygote was more frequent in the patients with gastric cancer at the cardia than in those with cancer at the antral or corpus locations. (55.56% of cardia vs. 14.28% of corpus and antrum, p=0.024). The arginine allele was associated with antral and corpus location of gastric cancer and the proline allele was associated with cardial location (OR=3.25, p=0.026). Also, these polymorphisms do not seem to be associated with age, sex, smoking and alcohol consumption, cell differentiation, lymph node involvement, tumor stage and distant metastasis. CONCLUSIONS: The proline allele at p53 codon 72 is associated with adenocarcinoma of the gastric cardia, and the arginine allele is associated with cancer of the antral and corpus locations. These findings suggest that different genotypes of the p53 gene in different locations of stomach might implicate a different cause of tumor growth.     

The Pro variant of the p53 codon 72 polymorphism is associated with hepatocellular carcinoma in Moroccan population

Aim: Codon 72 polymorphism of the p53 gene has been implicated in cancer risk, and it has been suggested that it may have an impact on the clinical outcome of the disease. Our objective was to evaluate the association between p53 polymorphism at codon 72 and hepatocellular carcinoma (HCC) in the Moroccan population. Methods: Genomic DNA was extracted from peripheral blood cells of 96 patients with HCC and 222 controls without HCC matched for age, gender and ethnicity. Codon 72 polymorphism of p53 was identified by PCR-restriction fragment length polymorphism, confirmed by sequencing. Results: Patients with HCC had higher frequencies of Pro/Pro (13.5% vs. 6.3%, P < 0.02) than controls and consequently a 2.3-fold increased risk of liver cancer development (odds ratio [OR], 2.304; 95% confidence interval [CI], 1.014-5.234). In addition, we found a significant association between the p53Arg72Pro polymorphism and the female gender in HCC. Men with Pro/Pro genotype had a 1.57-fold increased risk for HCC, whereas the corresponding genotype in women had a 4.4-fold increased risk of HCC (OR, 4.4; 95% CI, 1.18-16.42). No correlation between the polymorphism and HCC risk was found when comparing the hepatitis C virus (HCV)-positive cases to HCV-positive controls. However, HCV-negative subjects and Pro/Pro genotype had a 3.31-fold increased risk for HCC. Conclusion: These results provide evidence that p53 polymorphism at codon 72 is a modifier of hepatocarcinogenesis, especially in women and HCV-negative subjects.