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)

The aim of this paper is to review and evaluate, in a comprehensive manner, the published data regarding the contribution of genetic polymorphisms to risk of esophageal cancer, including squamous cell carcinoma (SCC) and adenocarcinoma, in humans. All relevant studies available in MEDLINE and published before February 2007 were identified. Studies carried out in humans and that compared esophageal cancer patients with at least 1 standard control group were considered for analysis. One-hundred studies and 3 meta-analyses were identified. Eighty (80%) studies were conducted in Asian countries, particularly China including Taiwan (60 (60%) studies). The most intensively examined genes were those encoding carcinogen metabolic enzymes. The most widely studied gene was GSTM1 (15 studies), followed by ALDH2 (11 studies). ALDH2, MTHFR C677T, CYP1A1 Ile/Val, CYP1A1MspI, CYP2E1, GSTP1, GSTM1 and GSTT1 were examined by meta-analyses and significant relations were found between ALDH2*1*2 and the CYP1A1 Val allele and increased risk of esophageal cancer. In addition, increased risk of esophageal SCC was consistently associated with the ADH2*1*2 and the p53 codon 72 Pro/Pro genotypes. Cohort studies that simultaneously consider multiple genetic and environmental factors possibly involved in esophageal carcinogenesis are needed to ascertain not only the relative contribution of these factors to tumor development but also the contributions of their putative interactions.
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PMID:Genetic polymorphisms and esophageal cancer risk. 1767 67

Polymorphisms in phase I and phase II enzymes may enhance the occurrence of mutations at critical tumor suppressor genes, such as p53, and increase breast cancer risk by either increasing the activation or detoxification of carcinogens and/or endogenous estrogens. We analyzed polymorphisms in CYP1B1, GSTM1, GSTT1, and GSTP1 and p53 mutations in 323 breast tumor samples. Approximately 11% of patients exhibited mutations in p53. Women with mutations had a significantly younger age of diagnosis (P = 0.01) and a greater incidence of tumors classified as stage II or higher (P = 0.002). More women with mutations had a history of smoking (55%) compared to women without mutations (39%). Although none of the genotypes alone were associated with p53 mutations, positive smoking history was associated with p53 mutations in women with the GSTM1 null allele [OR = 3.54; 95% CI = 0.97-12.90 P = 0.06] compared to women with the wild-type genotype and smoking history [OR = 0.62, 95% CI = 0.19-2.07], although this association did not reach statistical significance. To test for gene-gene interactions, our exploratory analysis in the Caucasian cases suggested that individuals with the combined GSTP1 105 VV, CYP1B1 432 LV/VV, and GSTM1 positive genotype were more likely to harbor mutations in p53 [OR = 4.94; 95% CI = 1.11-22.06]. Our results suggest that gene-smoking and gene-gene interactions may impact the prevalence of p53 mutations in breast tumors. Elucidating the etiology of breast cancer as a consequence of common genetic polymorphisms and the genotoxic effects of smoking will enable us to improve the design of prevention strategies, such as lifestyle modifications, in genetically susceptible subpopulations.
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PMID:Polymorphisms in drug metabolism genes, smoking, and p53 mutations in breast cancer. 1768 74

The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.
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PMID:TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy. 1805 29

The aim of this report is to review and evaluate, in a comprehensive manner, the published data regarding the contribution of genetic polymorphisms to risk of head and neck cancer (HNC). All relevant studies available in MEDLINE and published before July 2007 were identified. Studies carried out in humans that compared HNC patients with at least 1 standard control group were considered for analysis. Two hundred and eighteen publications and 3 published meta-analyses were identified. Seventy-five (34%) studies were conducted in Asian, 72 (33%) in American, and 68 (31%) in European countries. The most widely studied gene was GSTM1 (58 studies), followed by GSTT1 (42 studies), GSTP1 (codon 105, 22 studies) and p53 (codon 72, 20 studies). GSTM1, GSTT1, GSTP1, XRCC1 codons 194 and 399, and CYP1A1 codon 462 were examined by meta-analyses, and significant relations were found between the GSTM1-null genotype and an increased risk for HNC. In addition, increased risk for HNC was associated consistently with the ALDH2*1/*2, p53 codon 72 Pro/Pro and EPHX1 codon 113 Tyr/His and His/His genotypes. Cohort studies that simultaneously consider multiple genetic and environmental factors possibly involved in carcinogenesis of the head and neck are needed to ascertain not only the relative contribution of these factors to tumor development but also the contributions of their putative interactions.
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PMID:Genetic polymorphisms and head and neck cancer risk (Review). 1842 22

The growing number of human cancers is the main reason for the search for new effective treatment strategies. The molecular basis for cancer transformation has to be elucidated in order to improve cancer treatment. It is stated that HNSCCs make up at least 5% of all registered malignant tumors in Poland. Exogenous factors influence HNSCC etiology. The prevalence of HNSCC is increased by several carcinogens, including tobacco smoke, life style, and others, such as oncogenous viral infections. It is more often emphasized that endogenous agents can also increase the risk of HNSCC development, especially genetic factors. The most recently characterized genetic factors for head and neck cancer are mutations in xenobiotic metabolism enzyme genes (GSTM1, GSTT1, GSTP1), suppressors mutations (TP53, RB1, BRCA1, ATM), polymorphisms of DNA repair genes (OGG1, XRCC1, XPD, RAD51), and mutations in mitochondrial DNA. It has been observed that single-gene polymorphisms could affect treatment, whereas the coincidence of other gene mutations may increase the risk of human head and neck cancer development.
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PMID:[Genetic predeterminations of head and neck cancer]. 1883 34

The esophageal squamous cell carcinoma is multifactorial disease involving genetic and environmental factors. The paper presents most important human data on the polymorphisms of selected genes that have been linked with higher risk of the neoplasm. The most widely studied group were genes encoded molecules engaged in biotransformations of xenobiotics, in particular potential carcinogens, like alcohol (ADH2) and aldehyde (ALDH2) dehydrogenases, various isoenzymes of cytochrome P450 (CYP1A1, CYP2E1) and glutathione S-transferase (GSTM1, GSTT1, GSTP1). High interest was also put for polymorphism in DNA repair genes, i.e., OGG1, XRCC1, XPD, XPG and MGMT as well as genes associated with nucleotide biosyntesis like methylenotetrahydrofolate reductase and thymidylate synthase and in control of cell cycle and apoptosis e.g., p53, Fas, FasL or TNF. Furthermore, it was revealed that predisposition to cancer in certain individual could be determined by coexistence of unprofitable allele of a few genes. Introduction of genetic screening test allows effective, purpose-oriented methods of prevention and in patients suffered from the cancer--application of optimal therapy and minimization of side-effects.
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PMID:[Genetic base of esophageal squamous cell carcinoma susceptibility]. 1938 10

Polymorphisms of glutation-S-transferase (GSTM1, GSTT1 GSTP1) and methylentetrahydrofolate reductase (MTHFR) genes have been studied in DNA from blood lymphocytes of 18 patients with Down's syndrome and 61 controls. Frequencies of normal alleles of GST genotypes were lower in patients as compared to the controls. A DNA analysis of 11 patients and 17 controls revealed the presence of mutations in region 246-250 of exon 7 of the p53 gene in 4 patients. Mutations were not found in the control group. Due to the small sample size, the results of this study should be interpreted with caution and need replication in larger studies.
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PMID:[Gene polymorphisms in patients with Down's syndrome]. 1949 10

Colorectal cancer is the second most frequent cause of death among malignant diseases. The mortality of head and neck cancer in Hungary increased by 265 percent in the last thirty years. Both malignancies belong to the most current public health problems in Hungary. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. In case of head and neck cancer the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 gene were analyzed. Intraoperative removed tissue samples were processed and cancer free human samples were used as matched controls. The formalin fixed samples were deparaffinized and digested with proteinase K. Genotyping was performed by PCR amplification, and in case of head and neck cancer a PCR-RFLP method was applied. No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant difference in survival was found between the GSTM1 and p53 gene variants in Dukes'B stage colorectal patients. The survival difference among the XRCC1 194 alleles by head and neck patients in clinical stage III proved to be also significant. The complex analysis of this type of genetic variants may be the future way of the personal risk assessment and the real chance for personal therapy.
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PMID:[Genetic polymorphism in patients with colorectal and with head and neck cancer]. 1964 19

Lung cancer is a major cause of cancer-related death in developed countries, and its incidence in developing countries is increasing. In Thailand, cancer incidences differ greatly from region to region, and lung cancer is the most common cancer in the northern Thai population. The polymorphic frequency of 10 genetic susceptibility genes and their association with lung cancer were examined in a northern Thai population: CYP1A1 (MspI), CYP1A1 (Ile462Val), CYP2E1 (PstI), CYP2E1 (DraI), GSTM1, GSTT1, MPO (AciI), OGG1 (Ser326Cys), TP53 (Arg72Pro), and MMP1(AluI). The 173 subjects were 91 lung cancer patients and 82 healthy volunteers. Although no significant association between any single genetic variant and lung cancer risk was observed, when genetic variants were analyzed in combination, a significant effect on lung cancer risk was found for the variant allele in a combination of five genes involved in oxidative stress and inflammatory response: GSTM1 (null), MPO (-463A), OGG1 (326Cys), TP53 (72Pro) (alias p53), MMP1 (2G). With a reference group of individuals carrying at least two wild-type genotypes of these five genes, it was found that an individual carrying three or more variant genotypes is at significantly higher risk of developing lung cancer with the increasing of odds ratios (OR) in concurrence with the number of variant genes. The OR was 2.41 (95% CI = 0.76-7.64), 3.90 (95% CI = 1.23-12.34), and 5.20 (95% CI = 1.31-20.54) for individuals carrying three, four, and five variants, respectively. After stratifying by sex, the OR was higher for women: OR 4.05 (95% CI = 0.44-36.94), 9.00 (95% CI = 0.95-84.89) and 18.00 (95% CI = 1.49-216.62) for three, four, and five variant genotypes, respectively. This augmented effect on lung cancer risk of variant genes involved in oxidative stress and inflammatory response in women with a low prevalence of smoking indicates their modifying effect on other risk factors, such as environmental cigarette smoke, air pollution, radon radiation, or infection of the airway. Confirmation would require further investigations with larger sample sizes.
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PMID:Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women. 1996 14

Northeast region of India shows high incidence of tobacco-related cancer with widespread consumption of betel quid and tobacco in different forms. There is an increasing incidence of breast cancer and eminent use of tobacco in females in this region. Thus, we analysed the role of tobacco exposure and polymorphisms in detoxification enzymes in breast cancer risk. Polymorphisms in five gene variants (GSTT1, GSTM1, GSTP1, TP53 and CYP17) and four environmental exposure variables (tobacco smoking, tobacco chewing, betel quid chewing, alcohol) were analysed in 117 breast cancer cases and 174 cancer free controls. Multifactor dimensionality reduction identified betel quid chewing as the single main risk factor and women with betel quid chewing history had five times the risk of developing breast cancer [4.78 (2.87-8.00) 0.001]. In logistic regression analysis, GSTT1 null and GSTM1 null genotypes conferred 41% less [0.59 (0.34-1.03) 0.06] and 55% less [0.58 (0.30-1.02) 0.05] reduced risk to breast cancer, respectively. However, the risk increased in women with GSTP1 variant G allele which conferred 1.43 times [(0.96-2.11) 0.07] more risk to breast cancer. In conclusion this study suggests betel quid chewing as a significant risk factor for developing breast cancer. Moreover, the lack of detoxification enzymes GSTT1 and GSTM1 are associated with reduced breast cancer risk.
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PMID:Betel quid chewing as an environmental risk factor for breast cancer. 2072 66


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