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 present study was undertaken to examine the frequencies of GSTM1 (Null/Present), GSTP1 (Ile105Val) and p53 (Arg72Pro) genotypes and their relations to breast cancer susceptibility in South Indian women. This case - control study involved 250 consecutive breast cancer cases and 500 healthy controls matched in five-year age categories in the ratio of 1:2. Genotyping was performed by PCR for GSTM1, Real-Time Allelic discrimination assay for GSTP1 and PCR-CTPP for p53. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for the known risk factors for breast cancer. The frequencies for the GSTM1 Null genotype were 26% in the cases and 22% in the controls; for GSTP1 Ile/Ile, Ile/Val, Val/Val the frequencies were 46.6%, 41.9% and 11.5%, respectively, in cases and 46.0%, 43.8% and 10.2% in controls; for p53 Arg/Arg, Arg/Pro & Pro/Pro the frequencies were 26.4%, 50.0% and 23.6% in cases and 27.0%, 44.8% and 28.2% in controls. A nonsignificant elevation in breast cancer risk was observed among women who had the GSTM1 Null genotype (OR=1.24; 95% CI=0.83-1.84), the p53 Arg/Arg genotype (OR=1.28; 95% CI=0.81-2.03) and the Pro/Arg genotype (OR=1.49; 95% CI=0.99-2.25), and the GSTP1 Val/Val genotype (OR=1.1; 95% CI=0.64-1.91).
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PMID:Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and P53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer: a case control study from South India. 1769 41

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

A molecular genetic investigation of five genes: CFTR, GSTM1, GCTT1, MTHFR, and TP53 using DNA samples isolated from blood treated with either EDTA or stabilized heparin was conducted. Twenty DNA samples obtained from 10 persons. The results prove that heparin used as an anticoagulant instead of EDTA had no inhibitory effect on PCR and PCR/RFLP results, at least when DNA was isolated with a DNA-sorb-B kit. The results suggest that heparin-treated blood samples can be also used to study other genes.
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PMID:[Comparative analysis of molecular genetic studies using DNA samples isolated from blood treated with EDTA or heparin]. 1845 78

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

A CYP1A1 polymorphism has been associated with an increased risk for gallbladder cancer (GBC) in Japanese women. However, genetic risk factors for GBC in Hungary, where the population has a relatively high GBC incidence, has not been well studied. We therefore tested associations between CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1deletion, and TP53 Arg72Pro and GBC in Hungary. Genomic DNA was extracted from peripheral blood of 100 controls (52 men and 48 women) and from the tissue embedded in paraffin of 43 cases (6 men and 37 women). The case-control analysis was limited to females due to a small number of males. Of 37 female cases, 21 (56.8%) were diagnosed as adenocarcinoma, and the remaining 16 (43.2%) were classified as non-adenocarcinoma. The odds ratios (ORs) for the Ile/Val genotype and the Val allele were 8.9 (95% CI: 2.9-27.4) and 4.4 (95% CI: 1.7-11.1), respectively. The occurrence of the combined variant genotypes of CYP1A1 Ile462Val and GSTM1 (37.8% vs. 8.3%) or CYP1A1 Ile462Val and TP53 Arg72Pro (24.3% vs. 0%) was significantly higher in the cases than in the controls. The Ile/Val genotype was significantly associated with an increased risk of adenocarcinoma (OR 9.2; 95% CI: 2.6-32.6) and non-adenocarcinoma (OR 8.4; 95% CI: 2.2-32.4). Additionally, the Arg/Pro genotype increased risk of non-adenocarcinoma (OR 3.8; 95% CI: 1.2-12.8). The Val allele may contribute to the development of GBC not only in Japanese but also in Hungarian women. Our results provide a rationale for further studies of genetic variation on the risk of GBC in Hungary.
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PMID:Effect of genetic predisposition on the risk of gallbladder cancer in Hungary. 1899 8

Cigarette smoking has been identified as a risk factor for rectal cancer. Our investigation evaluates associations between active and passive smoking and TP53, KRAS2, and BRAF V600E mutations, microsatellite instability (MSI), and CpG Island Methylator Phenotype (CIMP) in rectal tumors. We examine how genetic variants of GSTM1 and NAT2 alter these associations in a population-based, case-control study of 750 incident rectal cancer cases and 1,201 controls. Detailed tobacco exposure data were collected in an extensive questionnaire. DNA from blood was examined for GSTM1 and NAT2 variants. Tumor DNA was assessed to determine TP53 (exons 5-8), KRAS2 (codons 12-13) and BRAF mutations, MSI (BAT26 and TGFbetaRII analysis), and CIMP (methylation of CpG islands in CDKN2A, MLH1, MINT1, MINT2 and MINT31). Cigarette smoking (>20 pack-years, relative to nonsmokers) was associated with increased risk of TP53 mutations (OR = 1.4, 95% CI 1.02-2.0), BRAF mutations (OR = 4.2, 95% CI 1.3-14.2) and MSI (OR = 5.7, 95% CI 1.1-29.8) in rectal tumors. Long-term environmental tobacco smoke (ETS) exposure of >10 hr/wk was associated with increased risk of KRAS2 mutation (OR = 1.5, 95% CI 1.04-2.2). All smoking indicators were suggestive of increased risk in CIMP+ rectal cancer. GSTM1 and NAT2 were generally not associated with rectal tumor alterations; however, we observed an interaction of ETS and NAT2 in TP53-mutated tumors (p < 0.01). Our investigation shows active smoking is associated with increased risk of TP53, BRAF and MSI+ in rectal tumors and is suggestive of increased risk of CIMP+ tumors. ETS may increase risk of KRAS2 mutations; association with TP53 mutations and ETS may be influenced by NAT2.
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PMID:Somatic alterations, metabolizing genes and smoking in rectal cancer. 1935 78

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


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