Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Prostate cancer is the most common cancer among men in many countries. Although the etiology of prostate cancer largely is unknown, both genetic and environmental factors may be involved. Advanced age, androgen metabolism, and heredity-race have been reported to be possible risk factors. On the other hand, several studies indicate that genetic polymorphisms in biotransformation enzymes play a role in prostate cancer development. In this study, association of the prostate cancer risk with genotype frequencies of the Phase I (CYP1A1) and Phase II (GSTM1 and GSTT1) biotransformation enzymes was investigated in 321 Turkish individuals (152 prostate cancer patients and 169 age-matched male controls). The presence or absences of the GSTM1 and GSTT1 genes were determined by a PCR-based method. Genotypes of CYP1A1 were determined by MspI-RFLP. The prevalence of GSTM1 null genotype in the cases was 64 percent, compared to 31 percent in the control group, indicating a strong association (OR = 4.08, 95%CI = 2.50-6.69). No association was observed between either GSTT1 null genotype or CYP1A1 polymorphism and prostate cancer incidence. No statistically significant association was observed between smoking status of the patients and any of the polymorphisms studied. In conclusion, results of this study indicate that only the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in Turkish population.
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PMID:Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population. 1646 91

The relationship between cigarette smoking and prostate cancer remains unclear. Any potential association may depend on the individuals' ability to metabolize and detoxify cigarette carcinogens--such as polycyclic aromatic hydrocarbons. To investigate this, we studied the association between prostate cancer and smoking, as well as the main and modifying effects of functional polymorphisms in genes that metabolize polycyclic aromatic hydrocarbons (CYP1A1 Ile(462)Val, microsomal epoxide hydrolase His(139)Arg) and detoxify reactive derivatives (GSTM1 null deletion, GSTT1 null deletion, GSTP1 Ile(105)Val and Ala(114)Val) using a family-based case-control design (439 prostate cancer cases and 479 brother controls). Within the entire study population, there were no main effects for smoking or any of the polymorphisms. However, the nondeleted GSTM1 allele was inversely associated with prostate cancer [odds ratio (OR), 0.50; 95% confidence interval (95% CI), 0.26-0.94] among men with less aggressive disease (Gleason score < 7 and clinical tumor stage < T2c) and positively associated (OR, 1.68; 95% CI, 1.01-2.79) with prostate cancer in men with more aggressive disease (Gleason score > or = 7 or clinical tumor stage > or = T2c). We also found a statistically significant negative multiplicative interaction between the GSTM1 nondeleted allele and heavy smoking (> 20 pack-years) in the total study population (P = 0.01) and in Caucasians (P = 0.01). Among Caucasians, heavy smoking increased prostate cancer risk nearly 2-fold in those with the GSTM1 null genotype (OR, 1.73; 95% CI, 0.99-3.05) but this increased risk was not observed in heavy smokers who carried the GSTM1 nondeleted allele (OR, 0.95; 95% CI, 0.53-1.71). Our results highlight the importance of considering genetic modifiers of carcinogens when evaluating smoking in prostate cancer.
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PMID:Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk. 1661 20

In this report, genetic polymorphism of phase I and II metabolic enzyme (CYP2E1, CYP17, GSTM1 and GSTT1) genes, living habits, and risk of prostate cancer (PCa) was studied in 163 patients with prostate carcinoma of Han nationality in Southern China and 202 age-matched controls. The genotypic polymorphism of CYP2E1, CYP17, GSTM1 and GSTT1 genes was analyzed by PCR-RFLP assay using genomic DNA isolated from peripheral blood lymphocytes. The significant risk factors for PCa included long-term exposure to toxicant (OR=2.27, 95%CI: 1.26-4.09), the tumor history of lineal consanguinity (OR=2.19, 95%CI: 1.30-3.67), sexual history before age 30 of no more than 8 times per month (OR=1.85, 95%CI: 1.22-2.81), deep inhalation of cigarette smoke (OR=2.01, 95%CI: 1.20-3.37) or heavy smoking (OR=1.67,95%CI: 1.01-2.76). Among individuals with long-term heavy smoking without tea-drinking habit, the risk increased significantly (OR=4.27, 95%CI: 1.62-11.24 and OR), 2.76, 95%CI: 1.20-6.32). CYP2E1 C1/C1 genotype significantly increased the risk for PCa (OR=1.61, 95%CI: 1.04-2.49) with an apparent interaction with alcohol (OR=2.07, 95%CI: 1.07-4.00). However, stratification by the amount of accumulative smoking revealed that among people with a heavy smoking history, the individuals with the CYP2E1 C1/C1 genotype (OR=2.55, 95%CI: 1.20-5.43) and the individuals with GSTT1 null genotype (OR=2.23, 95%CI: 1.09-4.57) showed a significantly increased risk. Any other significant results with GSTM1 or CYP17 genes were not observed in this research. Individuals with more sensitive genotypes (from one to four) were at an increased risk. The data show that, in the development of PCa, there are many interactions among predisposing genotypes and genetic polymorphisms and unhealthy living habits. Individuals with more susceptible genotypes and unhealthy habits such as prolonged exposure to smoking are at an increased risk.
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PMID:Polymorphisms of metabolic enzyme genes, living habits and prostate cancer susceptibility. 1672 Feb 91

Prostate cancer is the most common urologic malignancy, involving multiple factors. There is evidence that suggests that detoxification enzymes and growth factors may play a role in its development . The glutathione S-transferase (GST) enzymes detoxify several carcinogens and genetic polymorphisms in GSTM1, T1, and P1 (Ile105Val) have been reported to be associated with prostate cancer, mainly from blood samples. As expression studies suggest differential expression of different genes in tissues, we hypothesize that polymorphic status may be differently expressed for GSTM1, GSTT1 and GSTP1 gene in blood and tissues of prostate cancer patients and BPH controls, impacting on the development of prostate cancer. To study this, we extracted DNA from blood and tissue samples of patients undergoing biopsy procedures or transurethral resection of prostate tissue. Genotyping for GSTM1 and T1 was conducted by multiplex PCR and for GSTP1 by the PCR-RFLP method. Our results suggested no significant differences in frequency distribution of M1, T1 and P1 between blood and tissue samples of patients and controls, but in a few patients differences in polymorphic status were observed. However, they were not significant. Furthermore, we observed a significant risk of prostate cancer with null allele of GSTT1 and GSTM1 and Val allele of GSTP1, supporting our previous findings. A study with large sample size using radical prostectomy tissue now needs to be performed to attain a specific conclusion.
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PMID:Evaluating polymorphic status of glutathione-S-transferase genes in blood and tissue samples of prostate cancer patients. 1705 41

Previous studies suggest that enzymes involved in the androgen metabolic pathway are susceptibility factors for prostate cancer. Estrogen metabolites functioning as genotoxins have also been proposed as risk factors. In this study, we systematically tested the hypothesis that common genetic variations for those enzymes involved in the androgen and estrogen metabolic pathways increase risk for sporadic and familial prostate cancer. From these two pathways, 46 polymorphisms (34 single nucleotide polymorphisms, 10 short tandem repeat polymorphisms, and 2 null alleles) in 25 genes were tested for possible associations. Those genes tested included PRL, LHB, CYP11A1, HSD3B1, HSD3B2, HSD17B2, CYP17, SRD5A2, AKR1C3, UGT2B15, AR, SHBG, and KLK3 from the androgen pathway and CYP19, HSD17B1, CYP1A1, CYP1A2, CYP1B1, COMT, GSTP1, GSTT1, GSTM1, NQO1, ESR1, and ESR2 from the estrogen pathway. A case-control study design was used with two sets of cases: familial cases with a strong prostate cancer family history (n = 438 from 178 families) and sporadic cases with a negative prostate cancer family history (n = 499). The controls (n = 493) were derived from a population-based collection. Our results provide suggestive findings for an association with either familial or sporadic prostate cancer with polymorphisms in four genes: AKR1C3, HSD17B1, NQO1, and GSTT1. Additional suggestive findings for an association with clinical variables (disease stage, grade, and/or node status) were observed for single nucleotide polymorphisms in eight genes: HSD3B2, SRD5A2, SHBG, ESR1, CYP1A1, CYP1B1, GSTT1, and NQO1. However, none of the findings were statistically significant after appropriate corrections for multiple comparisons. Given that the point estimates for the odds ratio for each of these polymorphisms are <2.0, much larger sample sizes will be required for confirmation.
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PMID:Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer. 1750 24

Glutathione S-transferases (GSTs) are involved in the metabolism of a wide range of carcinogenic chemicals. In humans, cytosol GSTs are divided into eight classes: alpha (GSTA), mu (GSTM), pi (GSTP), theta (GSTT), tau (GSTZ), sigma (GSTS), omicron (GSTO) and kappa (GSTK). The allelic polymorphism of these enzymes is associated with variations in enzyme activity; hence, it may affect the concentration of activated carcinogenic chemicals in the body. In addition to the metabolism of chemical carcinogens, GSTs metabolize steroid hormones, compounds in the diet and other agents potentially involved in prostate carcinogenesis. Three genetic polymorphisms of GSTs, GSTM1*0 (null), GSTT1*0 (null) and GSTP1 A313G, have been well documented. No consistent associations between GSTM1, GSTT1 or GSTP1 genotypes and prostate cancer have been observed. Recent meta-analysis reports show that these polymorphisms of GSTM1, GSTT1 and GSTP1 are unlikely to be major determinants of susceptibility to prostate cancer.
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PMID:Genetic polymorphisms of human cytosol glutathione S-transferases and prostate cancer. 1815 51

The study of polymorphic variants of GSTT1, GSTM1 and GSTP1 genes from 61 patients with prostatic cancer (PC) has shown that incidence of 0/0 genotype GSTT1 and GSTM1 in PC patients was significantly higher of that in healthy men (n = 100) (34.4 and 15% in p = 0.007 and 60.7 and 43% in p = 0.04, respectively). PC risk in carriers of a GSTT1 deletion form was 2.97, CI95%--1.3-6.84, GSTM1--2.04 in CI95% 1.02-4.1. The analysis of combinations of pathological genotypes of xenobiotic biotransformation enzymes has demonstrated that 89.8% PC patients have a mutation in one of the genes GSTT1, GSTM1 or GSTP1.
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PMID:[Polymorphism of glutathion-S-transferase genes in patients with prostatic cancer]. 1857 65

The polymorphic inheritance of human drug-metabolizing enzymes, such as those encoded by the GST and CYP systems, has been implicated in both cancer risk and prognostic. In an effort to increase our understanding of the interaction between potential environmental exposure, lifestyle, and genetic factors in the predisposition and response to radiotherapy of prostate cancer patients, we examined GSTT1, GSTM1, GSTO1, GSTP1 and CYP1A1 genotypes in a Brazilian population. We studied 125 prostate cancer patients and 100 benign prostatic hyperplasia patients paired for ethnic and lifestyle characteristics. Lifetime occupational history, dietary patterns, cigarette-smoking, and other anamnestic data were obtained through interviews. Outcome was evaluated in 42 stage <or= T2a patients presenting a Gleason score <or= 6, PSA <or= 10 ng/ml, treated with radiotherapy and followed up for 12 to 34 months (15 +/- 8 months). None of the studied polymorphisms was found associated to prostate cancer risk either considered separately or in combination, in uni- or multivariate regression logistic analysis. Also, there was no association between genotypes and possible clinical factors of risk or any parameter of tumour aggressiveness at diagnosis or during follow-up. Patients' response to radiotherapy treatment was not associated to any genotype. In conclusion, our data suggest that GST and CYP1A1 genotypes are not associated with the susceptibility to prostate cancer or its outcome in the Brazilian population.
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PMID:Lack of association of GSTT1, GSTM1, GSTO1, GSTP1 and CYP1A1 polymorphisms for susceptibility and outcome in Brazilian prostate cancer patients. 1864 50

It has been postulated that individuals with GSTM1, GSTT1 deficiency and, GSTP1 (105Ile/Val transition) have increased susceptibility to carcinogens and are more likely to develop prostate cancer. In recent years, GST status has been extensively studied as a prostate cancer risk factor; however, the results are inconsistent. To re-examine this controversy, we have undertaken an updating meta-analysis of 29 studies with GSTM1 genotyping (4,564 prostate cancer cases and 5,464 controls), 22 studies with GSTT1 genotyping (3,837 cases and 4,552 controls), and 24 studies with GSTP1 genotyping (5,301 cases and 5,621 controls). The random effects odds ratio was 1.33 [95% confidence interval (95% CI): 1.15, 1.55; I(2) = 68.9%, P for heterogeneity = 0.00] for the GSTM1 null versus present genotype and 1.05 (95% CI: 0.86, 1.27; I(2) = 68.2%, P for heterogeneity = 0.00) for the GSTT1 null versus present genotype, and 1.06 (95% CI: 0.91, 1.24; I(2) = 71.5%, P for heterogeneity = 0.00) for the GSTP1-Val versus GSTP1-Ile allele. For GSTM1 polymorphism, similar results reached in Caucasians and Asians, with exception for Africans. No association between GSTT1 or GSTP1 polymorphisms and prostate cancer risk was detected in different racial. In conclusion, the major finding of our study suggested that GSTM1 polymorphism conferred an increasing risk of prostate cancer on a wide population basis, however, no relationship was found between GSTT1 and GSTP1 status and the risk of prostate cancer.
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PMID:An updating meta-analysis of the GSTM1, GSTT1, and GSTP1 polymorphisms and prostate cancer: a HuGE review. 1914 11


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