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)

Breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women (after lung cancer). The etiology of breast cancer is still poorly understood with known breast cancer risk factors explaining only a small proportion of cases. Risk factors that modulate the development of breast cancer discussed in this review include: age, geographic location (country of origin) and socioeconomic status, reproductive events, exogenous hormones, lifestyle risk factors (alcohol, diet, obesity and physical activity), familial history of breast cancer, mammographic density, history of benign breast disease, ionizing radiation, bone density, height, IGF- 1 and prolactin levels, chemopreventive agents. Additionally, we summarized breast cancer risk associated with the following genetic factors: breast cancer susceptibility high-penetrance genes (BRCA1, BRCA2, p53, PTEN, ATM, NBS1 or LKB1) and low-penetrance genes such as cytochrome P450 genes (CYP1A1, CYP2D6, CYP19), glutathione S-transferase family (GSTM1, GSTP1), alcohol and one-carbon metabolism genes (ADH1C and MTHFR), DNA repair genes (XRCC1, XRCC3, ERCC4/XPF) and genes encoding cell signaling molecules (PR, ER, TNFalpha or HSP70). All these factors contribute to a better understanding of breast cancer risk. Nonetheless, in order to evaluate more accurately the overall risk of breast tumorigenesis, novel genetic and phenotypic traits need to be identified.
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PMID:Understanding breast cancer risk -- where do we stand in 2005? 1578 78

The purpose of our study was to examine the roles of green tea drinking, other risk and protective factors, and polymorphism of susceptibility genes such as GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the risk of stomach cancer. A population-based case-control study was conducted in Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415 healthy control subjects. Epidemiological data were collected by in-person interviews using a standard questionnaire. Polymorphisms of susceptibility genes were assayed by PCR-RFLP techniques. A multigenetic index was created by summing up the number of risk genotypes. The data were analyzed using the logistic regression model. A reverse association between green tea drinking and risk of stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95% confidence interval [CI] = 0.34-1.01). Dose-response relationship was shown (p-trend < 0.05). A higher score on the multigenetic index was associated with increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI = 1.02-4.79) for those with at least 3 risk genotypes compared to those with <2 risk genotypes. Green tea drinking was suggested to have more than multiplicative interactions with alcohol consumption with an adjusted OR for interaction of 4.57 (95% CI = 1.62-12.89), and with higher multigenetic index with adjusted OR for interaction of 2.31 (95% CI = 0.88-6.03). The protective effect of green tea drinking was observed on the risk of stomach cancer and the possible effect modification by susceptibility genes was suggested.
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PMID:Green tea drinking and multigenetic index on the risk of stomach cancer in a Chinese population. 1585 51

The aim of our study was to identify occupational risk of irradiation exposure in the Czech nuclear power plant workers. We analyzed levels of chromosomal aberrations, a well-known biomarker of early biological effects and a predictor of cancer risk. We applied the conventional method of cytogenetic analysis and fluorescence in situ hybridization (FISH, whole chromosome painting for chromosomes 1 and 4, combined with a pancentromeric probe) to three groups: 123 subjects in the Temelin nuclear power plant (2 years in use), 114 subjects in the Dukovany nuclear power plant (20 years in use), and 53 matched controls from Ceske Budejovice. Nuclear power plant workers were divided into two groups: subjects with admittance into the monitored zone, and others. Following factors were also analyzed: GSTM1, GSTT1, GSTP1, XPD, XRCC1, hOGG1, p53, MTHFR, and MS gene polymorphisms, levels of vitamins A, C, E, and folate in plasma, and level of cotinine in urine. Long-term exposure to ionizing radiation in the monitored zone was 0.47+/-1.50 mSv (miliSievert) in the Temelin nuclear power plant and 5.74+/-9.57 mSv in the Dukovany nuclear power plant. Using the conventional cytogenetic analysis, we observed 1.90+/-0.95 and 1.82+/-1.19% AB.C. (percent of aberrant cells) in the Temelin nuclear power plant, and 2.39+/-1.01 and 2.33+/-1.04% AB.C. in the Dukovany nuclear power plant, for monitored zone workers and others, respectively. In the control group, we found 2.25+/-0.82% AB.C. Genomic frequency of translocations F(G)/100 measured by FISH was 1.89+/-1.40 and 2.01+/-1.68 in the Temelin nuclear power plant, and 2.48+/-1.93 and 2.14+/-1.62 in the Dukovany nuclear power plant for monitored zone workers and others, respectively. In the control group, F(G)/100 was 1.83+/-1.19. Following factors were identified as potential confounders by the conventional cytogenetic analysis: XPD-6, by the FISH: age, GSTP1 and p53Bst genotypes, long-term use of medication, alcohol consumption, and smoking. No association between the dose of irradiation and the level of chromosomal aberrations in any nuclear power plant was detected either by the conventional cytogenetic analysis or by FISH.
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PMID:Possible genetic damage in the Czech nuclear power plant workers. 1619 33

Quantitative and structural genetic alterations cause the development and progression of prostate cancer. A number of genes have been implicated in prostate cancer by genetic alterations and functional consequences of the genetic alterations. These include the ELAC2 (HPC2), MSR1, and RNASEL (HPC1) genes that have germline mutations in familial prostate cancer; AR, ATBF1, EPHB2 (ERK), KLF6, mitochondria DNA, p53, PTEN, and RAS that have somatic mutations in sporadic prostate cancer; AR, BRCA1, BRCA2, CHEK2 (RAD53), CYP17, CYP1B1, CYP3A4, GSTM1, GSTP1, GSTT1, PON1, SRD5A2, and VDR that have germline genetic variants associated with either hereditary and/or sporadic prostate cancer; and ANXA7 (ANX7), KLF5, NKX3-1 (NKX3.1), CDKN1B (p27), and MYC that have genomic copy number changes affecting gene function. More genes relevant to prostate cancer remain to be identified in each of these gene groups. For the genes that have been identified, most need additional genetic, functional, and/or biochemical examination. Identification and characterization of these genes will be a key step for improving the detection and treatment of prostate cancer.
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PMID:Prevalent mutations in prostate cancer. 1626 36

In contrast to most human malignancies, epidemiologic studies have frequently reported a reduced risk of differentiated thyroid cancer in tobacco consumers. Cytochrome P4501A1 (CYP1A1) gene variants may be related to an increased capacity to activate polycyclic aromatic hydrocarbons, producing highly reactive electrophilic intermediates that might damage DNA. Hence, the germline inheritance of a wild-type CYP1A1 gene may decrease the susceptibility for thyroid cancer. The present study was designed to investigate CYP1A1 (m1 and m2) role in thyroid tumorigenesis and its connection with GSTM1, GSTT1, GSTP1, GSTO1, and codon 72 of p53 genotypes. A total of 248 patients with thyroid nodules, including 67 benign goiters, 13 follicular adenomas, 136 papillary carcinomas, and 32 follicular carcinomas, and 277 controls with similar ethnic backgrounds were interviewed on their lifetime dietary and occupational histories, smoking habit, previous diseases, and other anamnestic data. DNA was extracted from a blood sample and submitted to PCR-restriction fragment length polymorphism assays. The wild-type CYP1A1m1 genotype was more frequent among papillary carcinoma patients (74.26%) than in the control population (62.45%; P=0.0147), reducing the risk for this type of cancer (odds ratio=0.564; 95% confidence interval=0.357-0.894). A multiple logistic regression analysis showed an inverse correlation between cigarette smoking (P=0.0385) and CYP1A1 germline inheritance (P=0.0237) with the susceptibility to papillary carcinomas. We were not able to find any correlation between smoking, clinical features, parameters of aggressiveness at diagnosis or during follow-up, and any of the GST or CYP genotypes considered separately or in different combinations. We suggest that CYP1A1 genotype might be associated with the reported reduced risk to papillary carcinomas among smokers.
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PMID:Smoking and susceptibility to thyroid cancer: an inverse association with CYP1A1 allelic variants. 1715 63

Glutathione S-transferases (GST) are enzymes involved in the conjugation of a number of human carcinogens, while p53 tumour suppressor gene is the most frequently mutated gene identified till now in human neoplasias. Typically, GSTM1 and GSTT1 genotyping are performed together, with several different protocol described and sometimes with the risk of misclassification due to "false negative", depending on the internal positive control employed. Here, we report a modification of the classical multiplex polymerase chain reaction (PCR) method, allowing the genotyping of GSTM1, GSTT1, together with a polymorphism within the intron 3 of TP53 tumour suppressor gene (a 16 base pairs (bp) duplication) in a single tube, with an appropriate internal positive control. To test the applicability of the method, the frequencies of the deleted alleles of GSTM1 and GSTT1 (null genotypes), and the 16 bp duplication of TP53 gene were assayed in a series of Caucasian DNA samples.
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PMID:Single tube genotyping of GSTM1, GSTT1 and TP53 polymorphisms by multiplex PCR. 1734 14

The capital city of Prague is one of the most polluted localities of the Czech Republic. Therefore, the effect of exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) adsorbed onto respirable air particles (<2.5mum) on chromosomal aberrations was studied in a group of policemen (males, aged 22-50 years) working in the downtown area of Prague and spending daily >8h outdoors (N=53). Age- and sex-matched healthy volunteers spending >90% daily time indoors were chosen as controls (N=52). Ambient air particles (PM10, PM2.5) and c-PAHs were monitored using versatile air pollution sampler (VAPS), and personal exposure was evaluated using personal samplers during working shift. Chromosomal aberrations were analyzed by conventional cytogenetic analysis and fluorescent in situ hybridization (FISH). Urinary cotinine plasma levels of vitamins A, E and C, folate, total cholesterol, HDL, LDL cholesterols and triglycerides were also analyzed as possible effect modifiers. Genotypes CYP1A1*2A, CYP1A1*2C, GSTM1, GSTP1, GSTT1, EPHX1, NAT2, hOGG1, XRCC1, XPD, p53 BstI, p53 MspI, MTHFR677, and MS2656 were determined by PCR-based RFLP assays. The following levels of air pollution were recorded during the study period (mean from HiVol sampling): PM10 62.6microg/m(3), c-PAHs 24.7ng/m(3), B[a]P 3.50ng/m(3). The conventional cytogenetic analysis did not reveal any differences between the group of policemen exposed to the ambient air pollution and the control group. The cytogenetic analysis by FISH analysis used the whole chromosome painting probes for chromosomes #1 and #4 (Cambio, UK). It detected a significant increase in all studied endpoints in the policemen compared to controls (% AB.C.=0.33+/-0.25 versus 0.24+/-0.18, p<0.05, F(G)/100=1.72+/-1.57 versus 1.25+/-1.11, p<0.05, AB/1000 (aberrations/1000 cells)=5.58+/-4.62 versus 3.90+/-3.06, p<0.05). CYP1A1*2C (Ile/Ile), XPD 23 (Lys/Lys), and XPD 6 (CC) genotypes were associated with an increase of aberrant cells by conventional method. Factors associated with an increased level of translocations by FISH included age, smoking, B[a]P-like DNA adducts (corresponding to the exposure of c-PAHs), folate, polymorphisms of CYP1A1*2C, GSTP1, EPHX1, p53 MspI and MTHFR. Ambient air exposure to c-PAHs significantly increased FISH cytogenetic parameters in nonsmoking policemen. We may conclude that FISH indicates that the city policemen in Prague represent a group of increased genotoxic risk. This is the first study that has reported a relationship between DNA adducts (biomarker of exposure) and chromosomal aberrations by FISH (biomarker of effect).
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PMID:Chromosomal aberrations in environmentally exposed population in relation to metabolic and DNA repair genes polymorphisms. 1741 42

The effect of exposure to organic compounds adsorbed onto respirable air particles (<2.5microm) on DNA adducts in lymphocytes was studied in a group of non-smoking policemen (N=109, aged 35+/-0.9 years) working in the downtown area of Prague and spending >8h daily outdoors. Personal exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) adsorbed on respirable particles was monitored in each subject for 48h before biological sampling. DNA adducts were analyzed by a (32)P-postlabelling assay, and total DNA adduct levels and B[a]P-like spots were determined. Further biomarkers included cotinine levels in urine to control for exposure to tobacco smoke, plasma levels of vitamins A, E and C and polymorphisms of metabolic genotypes (GSTM1, GSTP1, GSTT1, CYP 1A1-Msp I and Ile/Val, MTHFR, MS), DNA repair genotypes (XRCC1, hOGG1 and XPD exons 6 and 23) and the p53 gene (p53 Msp I and BstU I). All the biomarkers of exposure and effect were analyzed repeatedly during a period of one year at 2-3 month intervals (January, March, June, September 2004) to cover periods with high (winter) and low (summer) levels of air pollution. The highest personal exposure to c-PAHs was found in January (8.1+/-8.8ng/m(3)), while the other three sampling periods exhibited 3-4-fold lower c-PAH exposure. The total DNA adducts were only slightly elevated in January (2.08+/-1.60) compared to March (1.66+/-0.65), June (1.96+/-1.73) and September (1.77+/-1.77). B[a]P-like DNA adducts, however, were significantly higher in January than in the March and June sampling periods (0.26+/-0.14 vs. 0.19+/-0.12 and 0.22+/-0.13, respectively; p<0.0001 and p=0.017) indicating that c-PAH exposure probably plays a crucial role in DNA adduct formation in lymphocytes. No effect of individual metabololic or DNA repair genotypes on DNA adduct levels was observed. However, the combination of two genotypes encoding enzymes metabolizing c-PAHs - CYP 1A1 and GSTM1 - was associated with the levels of total and B[a]P-like DNA adducts under conditions of increased exposure to c-PAHs. Our study suggests that DNA adducts in the lymphocytes of subjects exposed to increased c-PAH levels are an appropriate biomarker of a biologically effective dose, directly indicating whether or not the extent of exposure to these compounds is related to an increased mutagenic and carcinogenic risk.
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PMID:Biomarkers of air pollution exposure--a study of policemen in Prague. 1749 40

DNA integrity was analyzed in the lymphocytes of 65 non-smoking city policemen during January and September 2004 using the comet assay combined with excision repair enzymes. Information about inhalation exposure was obtained by (1) stationary monitoring of PM2.5 and carcinogenic polycyclic aromatic hydrocarbons (cPAHs) during the sampling periods and (2) personal exposure monitoring of cPAHs 48h before blood sampling. The data were completed by a lifestyle questionnaire. Regardless of the season of the year, policemen working outdoors (exposed group) exhibited higher levels of DNA damage than those working indoors (controls). Within the exposed group, the levels of both unspecified and oxidative DNA damage detected in January significantly exceeded those found in September. The controls did not show analogous inter-seasonal variability. The winter levels of oxidative DNA damage positively correlated with exposure to cPAHs, probably reflecting increased oxidative stress as a result of high concentrations of PM2.5. In comparison with the wild type genotype, the carriers of at least one mutated allele, CYP1A1*2C (Ile/Val), MTHFR 2656 or MS 2656, and the EPHX1-medium phenotype appeared to be more susceptible specifically to the induction of oxidative DNA damage, while the p53 MspI mutation predisposed the carrier to a higher incidence of both breaks and oxidative lesions in DNA. In contrast, GSTM1-null and vitamin C tended rather to protect DNA integrity.
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PMID:Impact of air pollution and genotype variability on DNA damage in Prague policemen. 1759 Feb 89

The GSTM1 and GSTT1 genes reduce the effects of exposure to cytotoxic agents. Both genes have a null variant allele in which the entire gene is absent. On the other hand, a common polymorphism of the tumour suppressor P53 gene results in either arginine (A) or proline (P) at amino-acid position 72. The A and P alleles code proteins with distinct functions in apoptosis and DNA repair and have been associated with variable risks for several cancers. However, their roles in multiple myeloma (MM) are still unknown. We tested in study whether the GSTM1, GSTT1 and P53 genotypes altered the risk for MM in Brazilian patients. Genomic DNA from 106 patients and 230 controls were analysed by polymerase chain reaction-based methods for identification of the genotypes. Similar frequencies of the GSTM1, GSTT1 and P53 genotypes were seen in patients and controls. Individuals with the distinct genotypes had similar risks for disease. In contrast, an excess of the GSTM1 null (45.1 vs 17.2%, P = 0.009), the P53 PP+AP (70.4 vs 44.8%, P = 0.041) and the GSTM1 null plus P53 PP+AP (29.6 vs 10.3%, P = 0.004) genotypes were seen in MM patients at stage III compared with those at stages I + II. Our data suggest that the GSTM1, GSTT1 and P53 genotypes do not influence the risk for MM. However, the inherited presence of the variant codon 72 P53 allele, described here for the first time, and the absence of the GSTM1 detoxification pathway, seem to act in disease progression in our country.
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PMID:GSTM1 and codon 72 P53 polymorphism in multiple myeloma. 1765 13


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