Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associated with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16INK4alpha/p19ARF genes. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations. SSCP analysis indicated that only 9% (8/87) of the tumours had mutation in p16INK4alpha/p19ARF genes. Seventy-two tumours studied here were previously analysed for p53 mutations and 21% (15/72) of them were found to have mutations in p53 gene. Only one tumour was found to have mutation at both p53 and p16INK4alpha/p19ARF genes. Thus, the mutation rates observed were 21% for p53, 9% for p16INK4alpha/p19ARF, and 1% for both. Sequencing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) transversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine to a termination codon at p16INK4alpha gene codon 80 and the same mutation will alter codon 94 of p19ARF gene from CCG to CTG (proline to leucine). These results suggest that p16INK4alpha/p19ARF mutations are less frequent than p53 mutations in Indian oral SCCs. The p53 and p16INK4alpha/p19ARF mutational events are independent and are mutually exclusive suggesting that mutational inactivation of either p53 or p16INK4alpha/p19ARF may alleviate the need for the inactivation of the other gene.
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PMID:The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas. 1067 93

A. Storey et al. [Nature (Lond.), 393: 229-234, 1998)] reported a 7-fold increased risk of cervical cancer associated with having an Arg/Arg polymorphism at codon 72 of p53 compared with the Pro/Arg heterozygotes (odds ratio, 7.4; 95% confidence interval, 2.1-29.4). Complementary in vitro studies suggested that the HPV E6 oncoprotein more readily targets the arginine form, as opposed to the proline form, of p53 for degradation. We investigated the impact of this polymorphism in a population-based case-control study of invasive cervical cancer. Using a PCR assay to detect the p53 codon 72 polymorphism, we tested blood samples from 111 women with invasive squamous cell cancer of the cervix identified by a population-based registry and 164 random-digit telephone-dialed controls. The distribution of the genotype among control women was 38% heterozygous, 7% proline homozygous, and 55% arginine homozygous, and among the cases was 38%, 6%, and 56%, respectively. There was no increased risk of squamous cell invasive cervical cancer associated with homozygosity for the arginine allele (odds ratio, 1.0; 95% confidence interval, 0.6-1.7). Furthermore, there was no modification of this result by human papillomavirus (HPV) DNA status of the tumor, age, or smoking status. Among controls, there was no association between the polymorphism and HPV-16 L1 seropositivity. However, among case subjects, the codon 72 polymorphism may be related to HPV 16L1 seropositivity status.
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PMID:The p53 Arg72Pro polymorphism, human papillomavirus, and invasive squamous cell cervical cancer. 1069 87

Human papilloma virus (HPV) has been implicated in skin cancer. Also, in human populations, the p53 gene is polymorphic at amino acid 72 of the protein that it encodes. The association between p53 polymorphisms and HPV-associated skin cancer risk has been examined, but the results were conflicting. It was revealed that the arginine form of p53 is more susceptible to degradation by the HPV E6 protein than the proline form and that patients with the arginine form have a higher risk of developing cancer than those with the proline form. The purpose of this study was to examine whether p53 Arg at the polymorphic position 72 could represent a risk factor for patients with high risk HPV-associated malignant skin lesions. The study was conducted on 29 high risk HPV-related skin lesions from Greece. Blood samples from 61 healthy individuals were used as controls. HPV-8 was the most frequent type. There was a difference in the distribution of p53 genotypes between high risk HPV-skin lesions and the controls, and the allele frequency of p53 Arg/Arg was much higher than the controls (65.5% versus 20%). Therefore, it is suggested that p53 Arg homozygosity could represent a potential risk factor for tumorigenesis of the skin.
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PMID:P53 codon 72 polymorphism as a risk factor in the development of HPV-associated non-melanoma skin cancers in immunocompetent hosts. 1071 58

A common polymorphism of the wild type p53 is known at codon 72 of exon 4, with 2 alleles encoding either arginine (CGC, p53Arg) or proline (CCC, p53Pro). A recent study suggested that this polymorphism affects the susceptibility of p53 protein to human papillomavirus E6 oncoprotein mediated degradation and that individuals homozygous for p53Arg are seven times more susceptible to HPV-associated carcinogenesis of the cervix than heterozygotes. To examine whether the p53Arg genotype could be a risk factor for HPV-associated cervical carcinomas in the Korean population, we analyzed the p53 codon 72 polymorphism status of HPV-positive invasive cervical carcinomas from 52 Korean women and 103 healthy control samples. The proportion of individuals homozygous for p53Arg, homozygous for p53Pro, and heterozygous for the two alleles were 40%, 19%, and 41% in normal healthy controls; 42%, 17%, and 40% in women with HPV-positive invasive cervical carcinoma. There were no significant differences in the distribution of p53 genotypes between controls and cervical carcinomas. This finding indicates that the p53Arg genotype is not associated with an increased susceptibility to cervical carcinoma in Korean women.
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PMID:p53 codon 72 polymorphism and risk of cervical carcinoma in Korean women. 1071 11

Human papilloma virus (HPV) has been implicated in cervical carcinoma, and the p53 gene is polymorphic at amino acid 72 of the protein that it encodes. The association between p53 polymorphisms and risk for HPV-associated cervical cancer has been examined, but the results have been conflicting. It has been reported that patients with the arginine form have a higher risk of developing cervical cancer than those with the proline form. The purpose of this study was to examine whether p53 Arg at the polymorphic position 72 could represent a risk factor for women with high-risk HPV-associated premalignant and malignant cervical lesions. The study was carried out on 60 smears from patients with high-risk HPV-related cervical lesions. Also, 74 HPV-negative normal smears and 61 normal blood samples were used as controls. HPV-18 was the most frequent type. There was a difference in the distribution of p53 genotypes between high-risk HPV-cervical lesions and the normal samples. The allele frequency of p53 Arg/Arg was much higher than the normal samples (46.5% versus 20.5% in HPV-negative normal smears and 20% in blood samples). Based on the findings of this study, it is suggested that p53 Arg homozygosity could possibly represent a potential risk factor for the tumorigenesis of the cervix. Statistically significant correlation was not observed between the presence of Arg/Pro homozygosity or Arg/Pro heterozygosity and HPV typing.
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PMID:P53 codon 72 polymorphism as a risk factor in the development of HPV-associated cervical cancer. 1077 8

A case-control study was performed to investigate the risk of cervical cancer associated with p53 polymorphism at codon 72, encoding either arginine or proline. It has been recently suggested that the arginine isoform increases the susceptibility to invasive cervical cancer; however, data remain controversial. The polymorphism was examined by both allele-specific PCR and RFLP analysis in 101 patients with primary cervical cancer and in 140 healthy women of the same age and from the same geographical area. The distribution of p53 genotypes in cervical cancer patients and in controls was not significantly different (P = 0.445), and homozygosity for arginine at residue 72 was not associated with an increased risk for cervical cancer (odds ratio, 0.81; 95% confidence interval, 0.47-1.42; P = 0.52). Similarly, different genotype distribution and increased risk were not observed when patients versus controls were analyzed according to human papillomavirus status and cancer histotype. Therefore, no evidence of association between homozygosity for p53 arginine and cervical cancer was found in our population sample.
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PMID:p53 codon 72 polymorphism does not affect the risk of cervical cancer in patients from northern Italy. 1079 89

In 1998, Storey and co-workers suggested that individuals homozygous for arginine (Arg) at codon 72 of the p53 gene are about seven times more susceptible to human papillomavirus (HPV)-related carcinogenesis than heterozygotes. Since then, several studies from Northern Europe, Japan and the USA have failed to demonstrate a similar correlation. By contrast, a study in Brazil as well as one recent study in Italian and Swedish populations showed strong positive associations. We examined the frequency of p53 codon 72 polymorphism in samples from both invasive and intra-epithelial cervical neoplasias (CIN), and compared them with samples from healthy controls. All 88 samples came from women with a Greek ethnic background. Tissue specimens were collected from archival material with histologically diagnosed low-grade CIN (LGCIN), high-grade CIN (HGCIN) or cervical cancer (CxCa). As a control, we used cellular material newly collected by cytobrush from the cervices of 30 healthy women with normal cytological and colposcopical examinations. p53 Arg homozygosity (Arg/Arg) alone was associated with four-, six- or eight-fold increased risks for LGCIN, HGCIN or invasive cancer, respectively. The frequency of the p53Arg/Arg genotype and of the proline (Pro) allele showed significant linear trends according to the degree of severity of the lesion (P = 0.0007 and P = 0.0009, respectively). Exclusion of the ten HPV16/18-negative cases did not substantially alter the Arg/Arg frequency among the groups nor the significant linear trend. Our results confirm the initial findings of Storey and co-workers, as well as the data of the Brazilian and the recent European study, but do not accord with those of the other aforementioned studies. Variations in ethnic background, laboratory performance, verification of the HPV status, definition of controls, and sample size are the most plausible explanations for this controversy. In all our samples, the distribution of the p53 alleles fits the Hardy-Weinberg equilibrium and the 0.48 frequency of the Pro allele in our controls accords well with the percentages previously reported for different ethnic groups as characteristic of the assumed north-south cline. Some authors assert that the discrepancy in the results could not be attributed to differences in the methods; however, the Brazilian study emphasized the effect of inter-laboratory variation in detecting the association between p53 polymorphism and cervical cancer. Regarding the control group, our samples were only from women with a cytologically and colposcopically benign cervical epithelium. We think that simply choosing 'normal volunteers' for collecting control DNA blood samples without knowing the status of their cervical epithelium is indeed a possible source of bias. Finally, it is very unlikely that loss of heterozygosity at the p53 locus could be a factor interfering with the allelotype distribution. Our present small study results, which suggest a biologically relevant association, provide strong evidence that homozygous arginine at codon 72 of p53 may confer a higher susceptibility to HPV-associated intra-epithelial and invasive cervical neoplasia.
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PMID:p53 codon 72 polymorphism and risk of intra-epithelial and invasive cervical neoplasia in Greek women. 1083 May 78

Human papillomavirus type 16/18 (HPV-16/18) is implicated in the pathogenesis of squamous cell carcinoma (SCC) of the cervix and esophagus. The arginine allele at codon 72 of p53 was found to be more susceptible to degradation by HPV E6 protein than is the proline allele in vivo, thus resulting in a high frequency of cervical SCC in individuals homozygous for arginine at the codon. There are controversial results from several clinical studies of cervical SCC. In the present study, encoding regions of p53 codon 72 and HPV-16/18 E6 were directly sequenced, using pairs of primary esophageal SCC tissue and corresponding normal mucosa, which were from 75 patients (Japanese, n = 38; Chinese, n = 37). The arginine allele alone was detected in 70.6% (12 of 17) of HPV-positive cases but only in 43.1% (25 of 58) of HPV-negative cases (P < 0.05). In contrast, such a significant correlation between p53 polymorphism and HPV infection was not evident in corresponding normal mucosae. Because our findings between tumor specimens and the normal mucosae differed, we suggest that the frequent loss of proline allele in HPV-associated carcinogenesis of the esophagus major plays some role. The particular type of p53 polymorphism may indicate a potential candidate for HPV-associated SCC.
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PMID:p53 polymorphism in human papillomavirus-associated esophageal cancer. 1085 Apr 7

The role of dynamin GTPases in the regulation of receptor-mediated endocytosis is well established. Here, we present new evidence that the ubiquitously expressed isoform dynamin-2 (dyn2) can also function in a signal transduction pathway(s). A </=5-fold increase of dyn2 relative to endogenous levels activates the transcription factor p53 and induces apoptosis, as demonstrated by reduced cell proliferation, DNA fragmentation, and caspase-3 activation. Dyn2-triggered apoptosis occurs only in dividing cells and is p53 dependent. A mutant defective in GTP binding does not trigger apoptosis, indicating that increased levels of dyn2.GTP, rather than protein levels per se, are required to transduce signals that activate p53. A truncated dyn2 lacking the COOH-terminal proline/arginine-rich domain (PRD), which interacts with many SH3 domain-containing partners implicated in both endocytosis and signal transduction, triggers apoptosis even more potently than the wild-type. This observation provides additional support for the importance of the NH(2)-terminal GTPase domain for the apoptotic phenotype. All described effects are dyn2-specific because >200-fold overexpression of dyn1, the 70% identical neuronal isoform, has no effect. Our data suggest that dyn2 can act as a signal transducing GTPase affecting transcriptional regulation.
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PMID:Evidence that dynamin-2 functions as a signal-transducing GTPase. 1089 63

In this study we investigated the involvement of p53 polymorphism at codon 72, the infection and typing of human papillomavirus (HPV) and the correlation of p53 polymorphism with HPV type and other clinicopathologic characteristics in 72 Hong Kong women with cervical cancer. We developed a simple and nonradioactive method for determining polymorphism at codon 72 of the p53 gene. The homozygous p53 arginine allele (Arg/Arg) was detected in 22 (31%), the homozygous p53 proline allele (Pro/Pro) in 14 (19%) and the heterozygous allele (Arg/Pro) in 36 (50%) cases, respectively. Using the consensus primers MY11 and MY09, HPV infection was detected in 55 of 72 (76%) cases. The prevalent types were HPV-16 (55%), HPV-18 (16%) and HPV-58 (9%). The number of HPV-positive cases with Arg/Arg, Pro/Pro and Arg/Pro were 17 (31%), 12 (22%) and 26 (47%), respectively. The p53 polymorphism at codon 72 was not significantly correlated with any of the HPV types (p > 0.05). No striking overrepresentation of homozygous arginine-72 p53 was observed in HPV-associated cervical cancer. The results in this study did not show that any p53 polymorphic form has a prognostic significance for cervical cancer.
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PMID:p53 polymorphism and human papillomavirus infection in Hong Kong women with cervical cancer. 1089 31


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