Dataset Information

Haplotype analysis of the XRCC1 gene and laryngeal cancer.

ABSTRACT:

Objective

Several polymorphisms in DNA repair genes have been extensively studied in association with various human cancers, including laryngeal cancer. The present study aimed to investigate the association between polymorphisms of the XRCC1 gene and laryngeal cancer in a Chinese population.

Methods

Five polymorphisms of the XRCC1 gene (rs3213403, rs1799778, rs1001581, rs3213282, and rs3810378) were genotyped by TaqMan in 234 patients with larynx cancer and 230 age- and sex-matched controls without cancer.

Results

The rs3213403, rs1799778, and rs3213282 polymorphisms of XRCC1 were associated with larynx cancer. Haplotype analysis indicated that CCA (odds ratio [OR], 5.707; 95% confidence interval [CI], 3.277-9.938; p<0.001), TGG (OR, 4.344; 95% CI, 2.804-6.732; p<0.001), ACA (OR, 1.615; 95% CI, 1.159-2.250; p=0.004), and GCG (OR, 1.702; 95% CI, 1.164-2.489; p=0.005) were associated with an increased risk for larynx cancer, respectively. However, TGA (OR, 0.518; 95% CI, 0.398-0.673; p<0.001) and ACC (OR, 0.314; 95% CI, 0.215-0.457; p<0.001) were associated with a decreased risk for larynx cancer.

Conclusions

The results indicated that XRCC1 genetic polymorphisms were associated with larynx cancer in a Chinese population.

SUBMITTER: Chen W

PROVIDER: S-EPMC4094024 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Haplotype analysis of the XRCC1 gene and laryngeal cancer.

Chen Wei W Xu Li L Wang Zhi-Yi ZY Xue Li-Jun LJ Xue Feng-Lei FL Jiang Man-Jie MJ Wang Qiu-Ping QP Zheng Hong-Liang HL

Genetic testing and molecular biomarkers 20140623 7

<h4>Objective</h4>Several polymorphisms in DNA repair genes have been extensively studied in association with various human cancers, including laryngeal cancer. The present study aimed to investigate the association between polymorphisms of the XRCC1 gene and laryngeal cancer in a Chinese population.<h4>Methods</h4>Five polymorphisms of the XRCC1 gene (rs3213403, rs1799778, rs1001581, rs3213282, and rs3810378) were genotyped by TaqMan in 234 patients with larynx cancer and 230 age- and sex-match ...[more]

PMID: 24956286

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Project description:Reduction in DNA repair capacity is associated with increased rates of birth defects, cancer, and accelerated aging. According to some earlier studies, genetic polymorphisms in DNA repair genes might influence the repair activities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, inter-individual and ethnic differences in DNA repair capacity have been observed in various populations. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely reported in different cancers. We conducted a case-control study to examine the role of genetic polymorphisms in XRCC1 Gln632Gln (rs3547), Arg399Gln (rs25487), Arg280His (rs25489), Arg194Trp (rs1799782) in the risk of laryngeal cancer in different ethnic groups in Xinjiang. This study included 58 laryngeal cancer patients and 120 healthy controls age- and sex-matched without cancer. The genotypes of XRCC1Gln632Gln (rs3547), Arg399Gln (rs25487), Arg280His (rs25489) and Arg194Trp (rs1799782) were analyzed by PCR-RFLP, and the odds ratio (OR) and 95% confidence interval (CI) were calculated using an unconditional logistic regression model. C/T (hybrid) and T/T (mutant) genotypes of XRCC1 Arg280His (rs25489) revealed no statistical significance in the risk of laryngeal cancer (P>0.05), whereas the genotypes of XRCC1 Gln632Gln (rs3547), Arg399Gln (rs25487), Arg280His (rs25489), Arg194Trp (rs1799782) showed a higher risk than the controls (P<0.01) in Han, Uygur, and Kazak nations. In conclusion, the current study suggests that XRCC1 Gln632Gln (rs3547), Arg399Gln (rs25487), and Arg194Trp (rs1799782) polymorphisms may be associated with laryngeal cancer risk in the Han, Uygur, and Kazakh populations in Xinjiang. Individuals carrying genotype Arg/Gln+Gln/Gln showed a greater risk than those carrying Arg/Arg for laryngeal cancer in the Han, Uygur and Kazakh ethnic groups, and the odds ratios are 1.47, 1.32, and 0.77.

Project description:Background and objectiveThe X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study.MethodsPubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status.ResultsA total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H, respectively).ConclusionsThis meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.

Project description:Background and objectivesStudies investigating the association between glutathione S-transferase M1 (GSTM1) gene polymorphism and laryngeal cancer risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible associations of GSTM1 gene polymorphism with laryngeal cancer risk.MethodsThe relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until May 2011 and selected on the basis of the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize association of GSTM1 polymorphism with laryngeal cancer susceptibility.ResultsSeventeen studies were included in the present meta-analysis (2,180 cases and 2,868 controls). The combined results based on all studies showed that GSTM1 null genotype was associated with increased laryngeal cancer risk (OR = 1.17, 95% CI = 1.04∼1.31). When stratifying for race, GSTM1 null genotype exhibited increased laryngeal cancer risk in Caucasians (OR = 1.15, 95% CI = 1.01∼1.31), while no significant association was detected in Asians (OR = 1.25, 95% CI = 0.80∼1.96). In the subgroup analysis based on source of controls, significant associations were observed in the population-based studies (OR = 1.15, 95% CI = 1.01∼1.31) yet not in the hospital-based studies (OR = 1.25, 95% CI = 0.93∼1.67). Furthermore, in the subgroup analysis based on sample size, significant associations were also found in studies with at least 50 cases and 50 controls (OR = 1.15, 95% CI = 1.02∼1.30) but not in studies with fewer than 50 cases or 50 controls (OR = 1.46, 95% CI = 0.87∼2.46).ConclusionsThis meta-analysis supported that the GSTM1 gene polymorphism was associated with laryngeal cancer, particularly in Caucasians, and these associations varied in different subgroup, which indicated that population-based study with larger sample size was more appropriate in design of future study.

Project description:BACKGROUND: X-ray repair cross-complementing group 1 (XRCC1) protein plays an important role in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of XRCC1 are suspected to have some relationship with response to chemotherapy and overall survival of lung cancer. This meta-analysis aimed to summarize published data on the association between the commonest SNPs of XRCC1 (Arg194Trp, C > T, rs1799782 and Arg399Gln, G > A, rs25487) and clinical outcome of lung cancer patients. METHODS: We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected using specific inclusion and exclusion criteria. Primary outcomes included objective response (i.e., complete response + partial response vs. progressive disease + stable disease) and overall survival (OS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were estimated. All analyses were performed using the Stata software. RESULTS: Twenty-two articles were included in the present analysis. XRCC1 Arg194Trp and Arg399Gln polymorphisms were significantly associated with response to treatment in lung cancer patients. Patients with C/T genotype, T/T genotype and minor variant T allele at Arg194Trp were more likely to respond to platinum-based chemotherapy compared with those with C/C genotype (C/T vs. C/C: OR, 2.54; 95%CI, 1.95-3.31; T/T vs. C/C: OR, 2.06; 95%CI, 1.39-3.06; C/T+T/T vs. C/C: OR, 2.42; 95% CI, 1.88-3.10). For XRCC1 Arg399Gln, G/A genotype, A/A genotype and minor variant A allele were associated with objective response in all patients (G/A vs. G/G: OR, 0.67; 95%CI, 0.50-0.90; A/A vs. G/G: OR, 0.43; 95%CI, 0.25-0.73; A/A+G/A vs. G/G: OR, 0.63; 95%CI, 0.49-0.83). Both G/A and A/A genotypes of XRCC1 Arg399Gln could influence overall survival of lung cancer patients (G/A vs. G/G: HR, 1.23; 95%CI, 1.06-1.44; A/A vs. G/G: HR, 2.03; 95%CI, 1.20-3.45). Interaction analysis suggested that compared with the patients carrying C/T+T/T genotype at XRCC1 194 and G/G genotype at XRCC1 399, the patients carrying 194 C/C and 399 G/A+A/A or 194 C/C and 399 G/G genotype showed much worse objective response. CONCLUSIONS: Genetic polymorphisms in XRCC1 gene might be associated with overall survival and response to platinum-based chemotherapy in lung cancer patients.

Dataset Information

Haplotype analysis of the XRCC1 gene and laryngeal cancer.

Objective

Methods

Results

Conclusions

Publications

Haplotype analysis of the XRCC1 gene and laryngeal cancer.

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