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)

Prostate cancer is a common malignancy that disproportionately affects African-American men. Environmental factors and variation in genes responsible for chemical and dietary carcinogen metabolism and DNA damage repair may modulate risk. Fourteen single nucleotide polymorphisms in NAT2 and four NER genes (ERCC1, XPF/ERCC4, XPG/ERCC5 and CSB/ERCC6) were genotyped in a case-control study of 254 African-American prostate cancer cases and 301 healthy controls from Washington, DC. Smoking status, BMI, age and genetic ancestry were included as covariates in the association analyses. We found that individuals homozygous for the XPG/ERCC5 -72C/T promoter polymorphism had a significant reduction in risk, for prostate cancer (OR=0.12; 95% CI=0.03-0.48). A haplotype trend regression test also revealed a protective effect for the haplotype bearing the T allele (P=0.003). In silica analyses suggest a functional implication for the promoter variant since it deletes a GCF transcriptional factor-binding site responsible for the downregulation of transcription. The protective effect of the promoter SNP on risk for prostate cancer was independent of smoking. In contrast, none of the SNPs typed for NAT2, ERCC1, ERCC4 and ERCC6 showed significant association with risk. Additional tests for genotype interactions were not significant. We note that there may be other factors, such as dietary exposures, which may modulate prostate cancer risk in combination with genetic variation within the NAT2 and NER genes. Our results, in combination with previous observations of LOH for ERCC5 in prostate tumors, provide further evidence for a role of XPG/ERCC5 in the etiology of prostate cancer.
Prostate Cancer Prostatic Dis 2008
PMID:NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans. 1802 84

Prostate cancer is the most commonly diagnosed cancer in men worldwide and is the second leading cause of cancer related mortality. Genetic background may account for the difference in susceptibility of individuals to different diseases and the relationship between genetic polymorphism and some diseases has been extensively studied. There are several common polymorphisms in genes encoding DNA repair enzymes, some of these polymorphisms are reported to result in subtle structural alterations of the repair enzyme and modulation of the repair capacity. The aim of the present study was to analyze the effect of XPG Asp 1104His and XRCC1 Arg309Gln polymorphisms on risk of prostate cancer in north Indian population. Statistically significant increased risk of prostate cancer was observed on individuals that posses His/His genotype of XPG (OR 2.53, 95% CI 0.99-6.56, P = 0.031). In this study 150 prostate cancer diagnosed patients, 150 healthy controls and 150 BPH (benign prostate hyper plasia) were recruited from north Indian population. Moreover, individuals that carried the Gln/Gln genotype of XRCC1 also showed statistically increased risk of prostate cancer (OR 2.06, 95% CI 1.07-4.00, P = 0.033). The Asp/Asp of XPG and Gln/Gln of XRCC1 in combination showed statistically increased risk of prostate cancer in cases (OR 3.29, 95% CI 1.09-10.16, P = 0.032).
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PMID:DNA repair genes polymorphism (XPG and XRCC1) and association of prostate cancer in a north Indian population. 2167 Sep 56

We aimed to investigate the association between genetic variants of the DNA repair genes XPG, CSB, XPC, CCNH, and MMS19L in the nucleotide excision repair (NER) pathway and risk of prostate cancer in a population in China. This study included 229 patients with newly diagnosed and histopathologically confirmed primary prostate cancer and 238 healthy controls. Genotyping of XPG, CSB, XPC, CCNH, and MMS19L were performed on a 384-well plate on the MassARRAY platform. Associations between the polymorphisms of the six genes and risk of prostate cancer were analyzed using conditional logistical regression. We found that the variant genotype TT of the XPG rs2296147 polymorphism was moderately significantly associated with a higher risk of prostate cancer compared to the wild-type genotype CC [odds ratio (OR)=1.79, 95% confidence interval (CI)=1.01-3.25], and individuals carrying the GG genotype of the CSB rs2228526 polymorphism were associated with an increased risk of prostate cancer (OR=1.95, 95%CI=1.02-3.74). The combination genotype of the XPG T allele and the CSB G allele was associated with a moderately higher risk of prostate cancer risk (OR=1.84, 95%CI=1.06-3.20). In conclusion, we found that polymorphisms in XPG rs2296147 and CSB rs2228526 were significantly associated with prostate cancer susceptibility in the Chinese population analyzed. Our results support the hypothesis that naturally occurring genetic variation of DNA repair genes increases susceptibility to prostate cancer.
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PMID:Polymorphisms of DNA repair-related genes with susceptibility and prognosis of prostate cancer. 2461 90

The genetic basis of prostate cancer (PC) is complex and appears to involve multiple susceptibility genes. A number of studies have evaluated a possible correlation between several NER gene polymorphisms and PC risk, but most of them evaluated only single SNPs among XP genes and the results remain inconsistent. Out of 94 SNPs located in seven XP genes (XPA-XPG) a total of 15 SNPs were assayed in 720 unselected patients with PC and compared to 1121 healthy adults. An increased risk of disease was associated with the XPD SNP, rs1799793 (Asp312Asn) AG genotype (OR=2.60; p<0.001) and with the AA genotype (OR=531; p<0.0001) compared to the control population. Haplotype analysis of XPD revealed one protective haplotype and four associated with an increased disease risk, which showed that the A allele (XPD rs1799793) appeared to drive the main effect on promoting prostate cancer risk. Polymorphism in XPD gene appears to be associated with the risk of prostate cancer.
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PMID:Common variants of xeroderma pigmentosum genes and prostate cancer risk. 2493 2

Genetic variants of nucleotide excision repair (NER) genes have been extensively investigated for their roles in the development of prostate cancer (PCa); however, the published results have been inconsistent. In a hospital-based case-control study of 1,004 PCa cases and 1,055 cancer-free controls, we genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of NER genes (i.e., XPC, rs2228001 T>G and rs1870134 G>C; XPD, rs13181 T>G and rs238406 G>T; XPG, rs1047768 T>C, rs751402 C>T, and rs17655 G>C; and XPF, rs2276464 G>C) and assessed their associations with risk of PCa by using logistic regression analysis. Among these eight SNPs investigated, only XPC rs1870134 CG/CC variant genotypes were associated with a decreased risk of prostate cancer under a dominant genetic model (adjusted odds ratio [OR] = 0.77, 95% confidence interval [CI] = 0.64-1.91, P = 0.003). Phenotype-genotype analysis also suggested that the XPC rs1870134 CG/CC variant genotypes were associated with significantly decreased expression levels of XPC mRNA in a mix population of different ethnicities. These findings suggested that XPC SNPs may contribute to risk of PCa in Eastern Chinese men.
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PMID:Polymorphisms in nucleotide excision repair genes and risk of primary prostate cancer in Chinese Han populations. 2797 99