Dataset Information

Susceptibility of XPD and hOGG1 genetic variants to prostate cancer.

ABSTRACT: DNA repair genes are important in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as those of the human homolog of 8-oxoguanine DNA glycosylase 1 (hOGG1) and excision repair cross-complementing rodent repair deficiency, complementation group 2/Xeroderma pigmentosum complementation group D (ERCC2/XPD), contribute to carcinogenesis. The aim of this study was to investigate the association of prostate cancer (PCa) risk with hOGG1 and ERCC2/XPD genetic variants. A case-control study of 200 cases including 100 PCa patients and 100 healthy subjects was conducted. Two single-nucleotide polymorphisms (SNPs) (ERCC2/XPD Arg156Arg and hOGG1 Ser326Cys) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results demonstrated a significant association of the XPD156 homozygous (AA, OR=3.80; 95% CI: 1.19-12.18; P=0.017), heterozygous (AC, OR=2.48; 95% CI: 1.02-6.35; P=0.033) and combined (AA+AC, OR=2.76; 95% CI: 1.18-6.84; P=0.011) mutant genotypes with a predisposition to high-risk PCa. In the stratified analysis, predisposition to high-risk PCa was also associated with the mutant genotypes of hOGG1 326 homozygous mutant (GG, OR=2.93; 95% CI: 1-8.74; P=0.033). The results also showed that the A allele of XPD Arg156Arg and the G allele of hOGG1 Ser326Cys were associated with an increased risk of PCa (OR=1.86 and 1.62; 95% CI: 1.13-3.06 and 1-2.67, respectively). In conclusion, the findings of this study demonstrated that the ERCC2/XPD Arg156Arg and hOGG1 Ser326Cys polymorphisms increased the susceptibility to high-risk PCa.

SUBMITTER: Zhou C

PROVIDER: S-EPMC3917053 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Susceptibility of XPD and hOGG1 genetic variants to prostate cancer.

Zhou Cheng C Xie Li-Ping LP Lin Yi-Wei YW Yang Kai K Mao Qi-Qi QQ Cheng Yue Y

Biomedical reports 20130530 4

DNA repair genes are important in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as those of the human homolog of 8-oxoguanine DNA glycosylase 1 (hOGG1) and excision repair cross-complementing rodent repair deficiency, complementation group 2/<i>Xeroderma pigmentosum</i> complementation group D (ERCC2/XPD), contribute to carcinogenesis. The aim of this study was to investigate the association of prostate cancer (PCa) risk with hOGG1 and ERCC2/XPD genetic variant ...[more]

PMID: 24649009

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Project description:Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) model. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg's and Egger's tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among aucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9-22.9) and 46.1% (95% CI = 40.2-52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09-1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase in risk can translate to a large number of excess lung cancer cases. As lung cancer is a multifactorial disease, further investigations of the gene-gene and gene-environment interactions on the hOGG1 polymorphism-associated lung cancer risk may help to better understand of the molecular pathogenesis of human lung cancer.

Project description:BACKGROUND:8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER). It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC. METHODS:We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping. RESULTS:No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58). CONCLUSION:The allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.

Project description:ObjectiveThis meta-analysis aimed to determine the relationships between XRCC1 Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and susceptibility to age-related cataract.MethodsMedline (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Various combinations of the keywords and MeSH terms were used to screen for potentially relevant studies, specifically "genetic polymorphisms" or "SNPs" or "variation" or "single nucleotide polymorphism" or "polymorphism" or "mutation" or "variant"; "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "XPD" or "Xeroderma Pigmentosum Complementation Group D Protein" or "ERCC2" or "XRCC1" or "XRCC1 DNA repair protein"; and "Cataract" or " Membranous Cataract" or " Pseudoaphakia." Meta-analyses were conducted using Stata 12.0 software. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (95% CI) were calculated.ResultsSix independent case-control studies were included in the meta-analysis. Our results indicated that the association between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C and increased susceptibility to age-related cataracts was statistically significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.17-1.44, p<0.001; XPD Lys751Gln: OR=1.25, 95% CI=1.12-1.40, p<0.001, respectively). Ethnicity-stratified analysis indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the development and progression of age-related cataract in China, India, and Turkey in the allele model and the dominant model. For the XPD Lys751Gln A>C variant, the association with the pathogenesis of age-related cataract in China and Turkey in the allele model and the dominant model was investigated.ConclusionsThe association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related cataract susceptibility observed in our meta-analyses supports the view that XRCC1 and XPD may play important roles in susceptibility to age-related cataract.

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Susceptibility of XPD and hOGG1 genetic variants to prostate cancer.

Publications

Susceptibility of XPD and hOGG1 genetic variants to prostate cancer.

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