Arg399Gln Polymorphism Research Articles

Assessment of the Link between XRCC1 Arg399Gln Polymorphism and Breast Cancer: a Meta-Analysis in a Single Ethnic Group.

Although various individual studies have been conducted to determine the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and breast cancer, the results remain inconclusive. To assess the influence of XRCC1 Arg399Gln polymorphism on the risk of breast cancer, a metaanalysis was performed in a single ethnic group. Eligible studies were identified via databases such as PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine, throughout February 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strengths of the associations. Ten studies documenting a total of 4732 breast cancer cases and 5677 controls were included in this metaanalysis. The results indicated no significant association between XRCC1 Arg399Gln polymorphism and breast cancer risk in both total analysis and subgroup analysis stratified by geographical areas and source of controls. This meta-analysis provided evidence that XRCC1 Arg399Gln variant might not be risk alleles for breast cancer susceptibility in the Chinese population. Further studies conducted in other ethnic groups are required for definite conclusions.

P2.03b-052 XRCC1 Arg399Gln and Rad51 G135C Gene Polymorphisms in Advanced Lung Adenocarcinoma in Serbia: Topic: Biomarkers

XRCC1 and Rad51 are proteins involved in DNA base excision repair and DNA homologous recombination/double-stranded-break repair mechanisms respectively. In non-small cell lung cancer, XRCC1 Arg399Gln polymorphism (disrupts protein-protein interactions), and Rad51 G135C polymorphism (enhances Rad51 promoter activity), have been proposed as factors that influence the overall and progression-free survival (OS and PFS) of patients treated with platinum-based chemotherapy. This study aimed to evaluate the influence of XRCC1 Arg399Gln and Rad51 G135C polymorphisms on the toxicity of chemotherapy and clinical outcome (OS, PFS) of advanced adenocarcinoma patients in Serbia. The study included 94 advanced lung adenocarcinoma patients, EGFR wild type, stage IIIB or IV (TNM7), performance status 0, 1 or 2, of Caucasian descent, who received standard platinum-based chemotherapy. XRCC1 and Rad51 genotyping was done by PCR-RFLP. Statistical analysis was performed using Chi-square, Fisher’s exact, Wilcoxon rank sum test, Breslow-Day test. Survival methodology was used for OS and PFS (Kaplan-Meier product limit method and Log-Rank test, Cox regression for HR). Statistical significance was considered for p<0.05. The group consisted of 62 males (66%) and 32 females (34%), median age at diagnosis 61 years (range 37-84), with 77 (82 %) of current or ex-smokers, and 65 (66%) of which presented with metastases at diagnosis. Follow up period was 1-55 months (median 11 months), during which 76 patients (81%) progressed, and 24 (19%) experienced chemotherapy-related toxicity of grade 3 and 4. Median (95%CI) PFS was 8,1 months (7.1-9.1), and median OS was 10 months (8.2-11.7). Genotype frequencies for XRCC1 Arg399Gln were 39.4% for Arg/Arg, 25.5% for Arg/Gln and 3.2% for Gln/Gln genotype. For Rad51 G135C frequencies were 61.7% for G/G, 26.6% for G/C and 1.1% for C/C genotype. Carriers of the XRCC1 Gln allele had a significantly shorter PFS (7.2m vs 9.5m, Breslow p=0.023) and OS (6.4m vs 15.7m, Breslow p=0.04), and were more susceptible to progression during chemotherapy. Although Rad51 genotypes alone had no statistically significant effect on PFS and OS, carriers of both XRCC1 Gln allele and Rad51 C allele had a 4 months shorter OS, the difference was not statistically significant. There were no statistically significant differences in the occurrence of high grade chemotherapy-induced toxicity according to the patients' XRCC1 and Rad51 genotypes. These results suggest that in the Serbian population XRCC1 and Rad51 genotyping could be a useful tool for predicting the clinical outcome with platinum-based chemotherapy in advanced EGFR wild-type adenocarcinoma patients.

Association between XRCC1 polymorphisms and the risk of cervical cancer: a meta-analysis based on 4895 subjects.

The present meta-analysis was intended to explore the relationship between the X-ray repair cross complementing 1 (XRCC1) polymorphisms (Arg194Trp, Arg280His and Arg399Gln) and cervical cancer risk. Several electronic databases were searched systematically and bibliographies of relevant papers were identified carefully. Then, a meta-analysis was performed based on eligible studies in various genetic models. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were employed to evaluate the strength of associations between the XRCC1 polymorphisms and cervical cancer risk. Additionally, heterogeneity analysis and sensitivity analysis were done if necessary. Totally, 11 articles involving 2092 cases and 2803 controls were included. Taken together, there was no obvious association between the Arg194Trp or Arg280His polymorphism and cervical cancer risk. Considering the great heterogeneity, subgroup analysis was done, but the pooled result remained stable. Nevertheless, the association between the Arg399Gln polymorphism and cervical cancer risk showed distinct statistic significance in the allele model, dominant model, homozygous model and heterozygous model. In view of the exiting heterogeneity, we did subgroup analysis stratified by ethnicity, resulting in the fact that the Arg399Gln polymorphism was related to the decreased risk of cervical cancer. The Begg's test and Egger's test were used to find no publication bias. To conclude, the current meta-analysis indicated that the XRCC1 Arg399Gln polymorphism decreased the risk of cervical cancer, while the Arg194Trp and Arg280His polymorphisms were not associated with cervical caner risk. Certainly, a well-designed large-scale multicenter study is warranted to confirm the finding.

Associations between XRCC1 Gene Polymorphisms and Coronary Artery Disease: A Meta-Analysis.

Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13–1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12–1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03–1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19–2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06–1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD susceptibility, specifically in Asian populations. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.

Gene-environment interactions between ERCC2, ERCC3, XRCC1 and cadmium exposure in nasal polyposis disease.

Gene-environment interactions have long been known to play an important role in complex disease aetiology, such as nasal polyposis (NP). The present study supports the concept that DNA repair gene polymorphisms play critical roles in modifying individual susceptibility to environmental diseases. In fact, we investigated the role of polymorphisms in DNA repair genes and cadmium as risk factors for Tunisian patients with NP. To the best of our knowledge, this is the first report on the impact of combined effects of cadmium and ERCC3 7122 A>G (rs4150407), ERCC2 Lys751Gln (rs13181) and XRCC1 Arg399Gln (rs25487) genes in the susceptibility to NP disease. Significant associations between the risk of developing NP disease and ERCC2 [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1-3.7, p = 0.023] and ERCC3 (OR = 2.2, 95% CI = 1.2-4.1, p = 0.013) genotypes polymorphisms were observed. Blood concentrations of Cd in NP patients (2.2μg/L) were significantly higher than those of controls (0.5μg/L). A significant interaction between ERCC3 (7122 A>G) polymorphism and blood-Cd levels (for the median of blood-Cd levels: OR = 3.8, 95% CI = 1.3-10.8, p = 0.014 and for the 75th percentiles of blood-Cd levels: OR = 2.7, 95% CI = 1.1-7.2, p = 0.041) was found in association with the risk of NP disease. In addition, when we stratified ERCC2, ERCC3 and XRCC1 polymorphism genotypes by the median and 75th percentiles of blood-Cd levels, we found also significant interactions between ERCC2 (Lys751Gln) and ERCC3 (7122 A>G) genotypes polymorphism and this metal in association with NP disease. However, no interaction was found between XRCC1 (Arg399Gln) polymorphism genotypes and Cd in association with NP disease.

Association of XRCC1 Arg399Gln and Arg194Trp polymorphisms with susceptibility to multiple autoimmune diseases: a meta-analysis.

The role of the X-ray repair cross-complementing gene 1(XRCC1) Arg399Gln and Arg194Trp polymorphisms has been involved in the investigations of susceptibility to multiple autoimmune diseases, but the results were inconsistent. Here, we have performed a meta-analysis to clarify the relationship between them. All appropriate case-control studies were searched in the PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) database. A meta-analysis was conducted on the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of autoimmune diseases. Pooled odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association. Fourteen relevant studies with a total of 2886 cases and 3257 controls were analyzed in our research. Analysis for the XRCC1 Arg399Gln polymorphism under recessive model (OR 1.53, 95% CI 1.07-2.18, P=0.019), dominant model (OR 1.36, 95% CI 1.04-1.77, P=0.026) and homozygous model (OR 1.67, 95% CI 1.07-2.62, P=0.024) indicated an association in the overall population, as well as in Caucasian populations under the recessive model (OR 1.73, 95% CI 1.03-2.91, P=0.039) and Asian populations under dominant model (OR 1.31, 95% CI 1.02-1.70, P=0.037). Stratification by disease indicated significant association between XRCC1 Arg399Gln and rheumatoid arthritis (RA) in all genetic models (P<0.05). However, there was no significant association between XRCC1 Arg194Trp polymorphism and autoimmune diseases in different genetic models. The current meta-analysis demonstrates that the XRCC1 Arg399Gln polymorphism confers susceptibility to autoimmune diseases in Asians and Caucasians and, in particular, shows that XRCC1 Arg399Gln polymorphism is associated with RA.

Association between X-Ray Repair Cross-Complementing Group 1 Arg399Gln Polymorphism and Cervical Cancer Risk: A Meta-Analysis in the Chinese Population

Background: Many studies have examined the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with cervical cancer susceptibility. However, the results of these studies are inconsistent. To further assess the effects of XRCC1 Arg399Gln polymorphism on the risk of cervical cancer in the Chinese population, a meta-analysis was performed. Methods: Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through December 2015. Pooled ORs and 95% CIs were used to assess the strength of the associations. Results: This meta-analysis identified 7 studies, including 1,589 cases and 2,235 controls. In the total analyses, a significantly elevated risk of cervical cancer was associated with variants of XRCC1 Arg399Gln (GA vs. GG: OR 1.30, 95% CI 1.13-1.49; AA + GA vs. GG: OR 1.27, 95% CI 1.02-1.58). In the subgroup analyses stratified by geographic areas and histopathology type, it revealed the significant result in South China. Conclusions: This meta-analysis showed that the XRCC1 Arg399Gln GA variant might be risk alleles for cervical cancer susceptibility in the Chinese population, and further studies in other ethnic groups are required to arrive at definite conclusions.

The Relationship Between XRCC1 Arg399Gln Polymorphism, Alcohol Consumption and Colorectal Cancer: One of the Alcohol Forbidding Reasons in Islam

Cancers start when cells in the body begin uncontrolled growth. Cancers are one of the major reasons of morbidity and death universally, and can spread to other organs of the body. colorectal cancer (CRC) is a type of cancer that starts in the colon or rectum. It has the third rank in occurrence of cancer and mortality in the US (1, 2). It is a very serious and dangerous problem worldwide (3). On the other hand, X-Ray repair cross-complementing protein 1 (XRCC1) plays an important role in the repair of DNA damage, and this repair implementation is via base lesions excision repair (BER) pathway (4). Free radical intermediates may generate DNA base lesions that should be removed via the BER. It should be noted that the reduced repair capacity due to XRCC1 polymorphisms is a venturesome factor for body’s health; Lunn et al. showed that the XRCC1 Arg399Gln polymorphism could cause defective DNA repair (5, 6). XRCC1 Arg399Gln polymorphism can result in lung cancer, leukemia, lymphoma, breast cancer and hepatocellular carcinoma (7-10). Our goal was to detect the relationship between XRCC1 Arg399Gln polymorphism and CRC and also to determine the efficacy of alcohol consumption on this relationship. Regarding the relationship between XRCC1 Arg399Gln polymorphism and CRC, some studies have shown that XRCC1 Arg399Gln polymorphism could cause CRC occurrence (11, 12). In Wu’s study, it was suggested that this polymorphism has a potential to increase CRC susceptibility (13). Similarly, Chang-Jiang Qin et al. detected the association between the polymorphism of XRCC1 Arg399Gln and CRC (14). Also two meta-analyses confirmed that XRCC1 Arg399Gln polymorphism is a predisposing factor for the development of CRC (15, 16). On the other hand, researchers also evaluated the interaction between three polymorphic sites of XRCC1 gene and drinking habit; the idea was based on the role of reactive oxygen species as relevant genotoxins that might account for the effects of alcohol; and they indicated a higher risk in people with Arg399Gln allele and alcohol drinking. Also, they suggested that chronic alcohol consumption could reduce XRCC1 protein activity (13). In addition, scholars found that the effect of high alcohol intake that increased the risk of CRC was more remarkable in carriers of the XRCC1 codons 194 Trp allele or 399 Gln allele (17-19), and as mentioned above, XRCC1 polymorphisms are repair capacity reducers, so in alcoholism, XRCC1 can’t become involved in the BER of alcohol-induced DNA damage. In conclusion, CRC is seriously and significantly associated with XRCC1 Arg399Gln polymorphism. The findings demonstrate that alcoholic drinks possess adverse effects on the colon and rectum because these drinks are associated with problems linked to XRCC1 Arg399Gln polymorphism in creation and development of CRC. Also, it should be noted that according to the Holy Quran, consumption of anything that causes drunkenness is forbidden such as alcoholic drinks (20). Finally, alcoholic drinks are hazardous factors in relation to CRC and this is one of the detected alcohol forbidding reasons in Islam. So via adherence to preachments of Islam about lack of alcohol consumption, one can promote their social and personal health.

Association between XRCC1 ARG399GLN, TP53 ARG72PRO and MDM2 T309G polymorphisms and the risk of breast cancer in women of the Kyrgyz population

Aim. To study an association between Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene polymorphisms and breast cancer (BC) rate in women of the Kyrgyz population Material and Methods. Genomic DNA was obtainedfrom the whole blood of 117 breast cancer patients and 102 cancer-free healthy women residing in the Kyrgyz Republic. XRCC1 (Arg399Gln), TP53(Arg72Pro) and MDM2 (T309G) genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. Results. Women with the 399Gln allele had 1,57 fold higher risk (OR=1,57; p=0,034) of developing breast cancer than cases without these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2,77 fold higher risk (OR=2,77; p=0,0010) of BC. Notably, haplotype analyses revealed a stronger association with breast cancer risk if compare with data of the genotype analysis at each locus alone. The combination of heterozygous XRCC1 (Arg399Gln) variant and TP53 (Arg72Pro) genes increased even more the risk of BC (OR=3,98; p=0,0059). The combination of Arg399Gln and T309G genotypes of - XRCC1 and MDM2 genes is significant association with risk of BC (OR=3,0; p=0,034). We showed the combinations of Arg399Gln, Arg72Pro and T309Ggenotypes of-XRCC1, TP53 andMDM2 genes is related to the strong association with risk of BC in Kyrgyz women (OR=6,40; p=0,025). Conclusion. The polymorphisms Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene are associated with an increased risk of BC in Kyrgyz females. Combinations of unfavorable genotypes of several candidate genes increase even more the risk of BC.

Quantitative assessment of the association between XRCC1 Arg399Gln and Arg194Trp polymorphisms and risk of cutaneous melanoma.

Accumulating evidence has suggested that the XRCC1 Arg399Gln and Arg194Trp polymorphisms might be related to cutaneous melanoma susceptibility. However, epidemiologic findings have been inconsistent. We have assessed reported studies by meta-analysis to perform a more precise estimation of the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of cutaneous melanoma. A total of seven eligible articles were selected for this meta-analysis, including 3454 cases and 3811 controls for the XRCC1 Arg399Gln polymorphism and 1256 cases and 1575 controls for the XRCC1 Arg194Trp polymorphism. Overall, no significant associations were found in all genetic models when the studies were pooled into the meta-analysis for the Arg399Gln and Arg194Trp polymorphisms. When stratified by source of control, significant associations were found for the Arg399Gln polymorphism in the population-based subgroup under AA versus GG [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.08-1.88]; the dominant model AA/GA versus GG (OR=1.25, 95% CI=1.04-1.51); and the recessive model AA versus GA/GG (OR=1.31, 95% CI=1.01-1.68). No significant associations were found for the Arg194Trp polymorphism in the subgroup analysis. This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism was a risk factor for cutaneous melanoma in population-based subgroup.

English

Abstract Coroner artery disease, the leading cause of morbidity and mortality worldwide, is an inflammatory disease. XRCC1 gene is playing the role of scaffolding protein for the base excision repair (BER) and single strand break (SSB) repair. The study population consisted of 402 participants living in the same region, classified into case group (n=201) and control group (n=201). Phenol-chloroform method was used to extract DNA from blood samples of the study participants. XRCC1 genotypes were determined using PCR/RFLP methods. No statistically significant difference was found between the study groups in terms of allele and genotype frequencies in XRCC1 Arg194Trp polymorphism. However, distribution of XRCC1 399Gln allele frequency was found to differ at a statistically significant level between the case and control groups (p=0.003; OR=1.56). Regarding the Arg/Arg genotype in Arg399Gln polymorphism, a statistically significant difference was detected in the distribution of Gln/Gln genotype (p=0.017; adj OR=3.11). Statistically significant differences were also recorded for Arg399Gln polymorphism among the smoking male participants with hypertension (p=0.009; p=0.031; p=0.032, respectively). The study suggests that XRCC1 399Gln/Gln genotype may be a significant risk factor for coronary artery disease.

XRCC1 and OGG1 Gene Polymorphisms and Breast Cancer: A Systematic Review of Literature.

Context:Known polymorphisms of DNA repair genes can be associated with the risk of many types of cancer. There is no consensus regarding association between XRCC1 and OGG1 with breast cancer (BC).Objectives:The aim of this study is to collect relevant published studies systematically.Data Sources:Sixty-two publications were identified through searching PubMed, PubMed Central, ISI web of knowledge, and reference list of related articles.Study Selection:We performed a systematic review according MOOSE guideline criteria. All longitudinal cohort and case-control studies investigating association of any type and grade of breast cancer with XRCC1 and OGG1 gene and their polymorphisms were eligible for initial inclusion.Data Extraction:Two authors screened titles and abstracts and extracted all needed information from eligible studies. Four research methodological components causing bias for the association between gene polymorphisms and breast cancer risk, including source of controls sampling, population ethnicity, sample size of studies and menopausal status of cases and controls was used for assessment of quality of studiesResults:A total of 14,793 breast cancer cases and 15,409 controls were included in assessment of XRCC1 Arg194Trp. Four studies showed significant association and one study showed protective effect of XRCC1 Arg194Trp and BC. A total of 7,716 cases and 7,370 controls were included for XRCC1 Arg280His. Only one study showed significant association of XRCC1 Arg280His and breast cancer (OR = 1.82 (1.06 - 3.15). A total of 27,167 cases and 31,998 controls were included to estimate association between XRCC1 Arg399Gln polymorphism and breast cancer. Seven studies showed significant association and one showed protective effect of XRCC1 Arg399Gln and BC. A total of 9,417 cases and 11,087 controls were included for OGG1 Ser326Cys. Among studies focused on OGG1 Ser326Cys, none showed significant association with breast cancer.Conclusions:Systematic search of major databases identify many studies addressing the relationship between BC and susceptible alleles in the base excision repair genes and the fact that there are many variations in the magnitude of association depending on inheritance model and the population of the study.

Single nucleotide polymorphisms in DNA repair genes and the risk of laryngeal cancer: A meta-analysis.

Laryngeal cancer is the most common type of head and neck cancer with poor prognosis and high relapse rate. Several genes involved in DNA repair pathways have been identified for their potential role in laryngeal cancer risk. However, the results remain inconclusive. The aim of this study was to investigate the association between polymorphisms of XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln and laryngeal cancer risk. Relevant case-control studies published between 2000 and 2015 were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of correction. Finally, total 16 articles (8 for XRCC1 Arg399Gln variant, 8 for XRCC3 Thr241Met variant and 7 for XPD Lys751Gln variant) were screened out, including 2242 laryngeal cancer cases and 3811 matched controls. Overall, our results found that only AA genotype of the XRCC1 gene Arg399Gln polymorphism under the homozygous model was associated with increased the risk of patients with laryngeal cancer (AA vs. GG: OR=1.29, 95% CI=1.00-1.65, P=0.05). This significant relationship was not detected between XRCC3 Thr241Met, XPD Lys751Gln polymorphisms and laryngeal cancer risk (P>0.05). In conclusions, our results suggested that XRCC1 gene Arg399Gln polymorphism might be a risk factor for laryngeal cancer. Future studies with large-scales, more ethnicities are still needed to further evaluate the role of these three genes mutations in laryngeal cancer susceptibility.

Association of DNA repair and xenobiotic pathway gene polymorphisms with genetic susceptibility to gastric cancer patients in West Bengal, India.

Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95% confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95% CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95% CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95% CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.

Role of XRCC1 gene polymorphisms in non-small cell lung cancer cisplatin-based chemotherapy, and their effect on clinical and pathological characteristics.

Non-small cell lung cancer (NSCLC) is the most common cancer globally. The XRCC1 protein interacts with ligase and poly(ADP-ribose) polymerase to repair cisplatin-induced DNA damage. The authors of previous studies have reported XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms and advanced NSCLC prognosis, but the results are inconclusive. We investigated the association between clinical outcome and XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms in advanced NSCLC patients treated with cisplatin. We recruited 252 patients with advanced NSCLC (TNM stages: IIIB and IV) and used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the polymorphisms. Patients with the TT genotype of XRCC1 Arg194Trp showed a significantly better response to chemotherapy than those with the CC genotype. The GA+AA genotype of Arg194Trp was correlated with better response to chemotherapy than the wild-type form. The TT genotype of Arg194Trp was associated with longer survival time than the CC genotype. The TT genotype of Arg194Trp was correlated with lower risk of death from all causes than the CC genotype. The Arg194Trp polymorphisms interacted with squamous cell carcinoma and affected overall survival of advanced NSCLC. However, there was no association between Arg399Gln and Arg280His polymorphisms and response to cisplatin-based chemotherapy and overall survival in advanced NSCLC. The results suggest that the TT genotype of Arg194Trp is significantly associated with better response to chemotherapy and longer overall survival of advanced NSCLC patients than the wild-type form. Our investigation offers insight into the influence of XRCC1 gene polymorphisms on the treatment outcome of advanced NSCLC.

Investigating the association between XRCC1 gene polymorphisms and susceptibility to gastric cancer.

We carried out a hospital-based case-control study to investigate the role of XRCC1 gene Arg399Gln, Arg280His, and Arg194Trp polymorphisms in susceptibility to gastric cancer. A total of 214 gastric cancer patients and 247 control subjects were recruited between March 2013 and March 2015, and polymorphism genotype frequencies were determined by polymerase chain reaction-restriction fragment length polymorphism. Using the chi-square test, we detected statistically significant differences in age (chi-square = 22.25, P < 0.001), gender (chi-square = 6.74, P = 0.01), and family history of cancer (chi-square = 4.73, P = 0.03) between the case and control groups. Logistic regression analysis revealed that the XRCC1 Arg194Trp TT genotype conferred increased susceptibility to gastric cancer compared to the CC genotype [odds ratio (OR) = 2.38, 95% confidence interval (CI) = 1.28-4.49]. Moreover, individuals carrying the T allele of this variant were found to be at moderately increased risk of this disease (OR = 1.56, 95%CI = 1.16-2.09). However, the XRCC1 Arg399Gln and Arg280His polymorphisms were shown to have no influence on the development of gastric cancer. In conclusion, we suggest that the XRCC1 gene Arg194Trp polymorphism is associated with gastric cancer susceptibility in the Chinese population.

Association between XRCC1 polymorphisms and laryngeal cancer susceptibility in a Chinese sample population.

Laryngeal cancer is the major malignant tumor affecting the upper respiratory tract. Previous studies have reported on the association between XRCC1 genetic polymorphisms and risk of laryngeal cancer, but with conflicting results. In this study, we attempted to assess the association between XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms and risk of laryngeal cancer in a Chinese population. A total of 126 laryngeal cancer patients and 254 control subjects were recruited to this study from the Second Medical College of Jinan University between December 2013 and May 2015. The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphic sites were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Our results revealed a significant association between the AA genotype of XRCC1 Arg280His [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.29-4.87, P = 0.01] and an increased risk of laryngeal cancer susceptibility compared to the GG genotype. Moreover, the A allele showed a higher risk of laryngeal cancer susceptibility compared to the G allele (OR = 1.63, 95%CI = 1.19-2.50, P = 0.002). In conclusion, the results of our study suggest that the AA genotype and A allele of the XRCC1 Arg280His polymorphism are associated with an increased laryngeal cancer risk in a Chinese population.

Interaction of XRCC1 Arg399Gln Polymorphism and Alcohol Consumption Influences Susceptibility of Esophageal Cancer.

Background. To explore the correlation between the Arg399Gln polymorphism and susceptibility to esophageal cancer in Korean and Han Chinese individuals in Harbin, China, and its potential interaction with alcohol consumption. Methods. This prospective study included 203 patients with esophageal squamous cell carcinoma; 88 were of Korean descent and 115 were of Han Chinese descent. A group of healthy controls included 105 participants of Korean descent and 105 of Han Chinese descent. Genotyping of the Arg399Gln locus of XRCC1 was performed by PCR-RFLP. Results. The allelic and genotypic frequencies were not significantly different between individuals with esophageal cancer and controls or between individuals of Korean and Han Chinese descent (P > 0.05). However, when individuals with the wild-type Arg/Arg genotype also consumed alcohol, the risk of esophageal cancer was lower (OR = 3.539; 95% CI = 2.039–6.142; P < 0.05). Conclusions. The XRCC1 Arg399Gln polymorphism does not appear to be associated with esophageal cancer in individuals of Korean or Han Chinese descent in Harbin, China. However, alcohol consumption may decrease the risk of esophageal cancer in persons with the wild-type genotype.

Association of XRCC1 gene polymorphisms and pancreatic cancer risk in a Chinese population

We conducted a case-control study to assess the role of the XRCC1 Arg399Gln, Arg280His, and Arg194Trp gene polymorphisms in pancreatic cancer susceptibility in a Chinese population. A total of 152 patients diagnosed with pancreatic cancer and 264 control subjects were enrolled in this study between March 2012 and October 2014. XRCC1 Arg399Gln, Arg280His, and Arg194Trp were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. As determined by the chi-squared test, a statistically significant difference was observed between pancreatic cancer patients and control subjects in regard to the genetic distribution of XRCC1 Arg399Gln (χ(2) = 16.13, P < 0.001). Using an unconditional regression analysis, we found that the TT genotype of Arg399Gln was associated with a significantly increased risk of pancreatic cancer (OR = 2.33, 95%CI = 1.20-4.51), and that the CT+TT genotype also significantly increased pancreatic cancer risk (OR = 1.58, 95%CI = 1.04-2.41), compared to the wild-type genotype. In conclusion, we found that XRCC1 Arg399Gln genetic variations are associated with pancreatic cancer development, whereas the XRCC1 Arg280His and Arg194Trp polymorphisms did not affect pancreatic cancer risk.

GSTP1 Ile105Val and XRCC1 Arg399Gln gene polymorphisms contribute to the clinical outcome of patients with advanced non-small cell lung cancer.

Glutathione S-transferase P1 (GSTP1) and X-ray repair cross-complementing group 1 (XRCC1) genetic variations may in-fluence the efficacy of chemotherapy in various cancers. We investi-gated the possible roles of GSTP1 Ile105Val and XRCC1 Arg194Trp, and Arg399Gln gene polymorphisms in the prognosis of advanced non-small cell lung carcinoma (NSCLC) patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, this study consecutively recruited 141 patients with advanced NSCLC from the First People's Hospital of Yunnan Province. Logistic regression analy-sis showed that individuals carrying the GG genotype were associated with a better response to chemotherapy than those with the wide-type genotype, with an adjusted odds ratio (95% confidence interval, CI) of 4.07 (1.06-25.06). Moreover, we observed that the AA genotype of XRCC1 Arg399Gln was correlated with a greater complete response + partial response to chemotherapy than that with the GG genotype (odds ratio = 2.71, 95%CI = 1.13-10.08). Based on the Cox hazard proportional model, the GG genotype of GSTP1 Ile105Val was found to be associated with a lower risk of death from all causes as compared to that with the AA genotype (hazard ratio = 0.07, 95%CI = 0.01-0.34). In summary, we suggest that GSTP1 Ile105Val and XRCC1 Arg399Gln polymorphisms could influence the response to chemotherapy and sur-vival of advanced NSCLC.