X-ray Repair Cross-complementing Group 1 Polymorphisms Research Articles

Study on the Association of XRCC1 Gene rs72484243 Polymorphisms with Increased Laryngeal Cancer Risk

Objective: To study the association of X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms with increased laryngeal cancer risk. Methods: A total of 120 individuals, comprising 60 patients with laryngeal squamous cell carcinoma (LSCC), and 60 healthy volunteers participated were selected. Blood samples were taken and analyzed, and 4 XRCC1 polymorphisms (rs145135970, rs1799780, rs25489, and rs72484243) were genotyped. Results: Gender, age, body mass index (BMI), and smoking habits were shown to be the high-risk factors for LSCC. Genotype and allele distributions for the 4 polymorphisms differed significantly between both groups (P < 0.05). Furthermore, carriers with the rs72484243GTGT- allele exhibited an increased risk of LSCC relative to those who had the rs145135970 GTGTGTGTGTGTGT- allele, the rs1799780 G-A allele, or the rs25489 C-T allele, as determined by binary logistic regression analysis (OR = 2.74, 95% CI: 1.27–5.91, P = 0.01), after accounting for possible co-factors like sex, age, BMI, drinking and smoking behavior, and special diet requirements. In addition, a TA haplotype and a GTGTGTGTGTGTGTTG haplotype were linked to LSCC in Chinese populations in a haploid association study of 4 SNP loci in the XRCC1 gene (P = 0.05 OR = 1.36, 95% CI = 1.1228–1.6406). Conclusion: Genetic polymorphisms of the XRCC1 gene at the rs72484243 site were correlated with an elevated risk of LSCC among the Xinjiang population.

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

Impact of XRCC3 rs861539 and XPD rs13181 gene polymorphisms on childhood acute lymphoblastic leukemia in Egyptian patients

Abstract Background There is mounting evidence that the genotypes of DNA repair proteins and susceptibility to certain malignancies are related. Few studies, however, have examined the role of the homologous repair gene X-ray repair cross-complementing group 3 (XRCC3) genotype and xeroderma pigmentosum complementation group D (XPD) in the development or prognosis of acute lymphoblastic leukaemia (ALL). Aim of the study In this study, we investigated the impact of XRCC3 rs861539 and XPD rs13181 polymorphisms on the risk of ALL. To the best of our knowledge, this is the first report of XRCC3 and XPD polymorphisms in ALL Egyptian patients. Methods Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to analyse XRCC3 rs861539 and XPD rs13181 gene polymorphisms in 96 patients with ALL and in 103 disease-free controls, who were of a similar age. Results ALL risk is lower in individuals with the homozygous variant TT genotype at XRCC3 rs861539. The heterozygous variant CT genotype of XRCC3 was connected to increased disease risk of ALL in males. Additionally, C allele frequency was noticeably higher than T allele frequency in pre B ALL. In this investigation, there was no correlation between the XPD Lys751 rs13181 polymorphism and risk of ALL. Conclusion Our research reveals that genetic variation in the genes for DNA repair may influence ALL susceptibility.

Arg399Gln XRCC1 Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck in Jordanian Patients.

Background and Objective:X-ray repair cross-complementing group1 (XRCC1) is a key protein in base excision repair and closely associated with the coordination of the base excision repair pathway. Many studies have focused on XRCC1 SNPs and have shown an associated between these SNPs and the risk of several types of cancers, including head and neck cancer. There are many single nucleotide polymorphisms XRCC1 gene (SNPs) and the most common SNP that result in amino acid substitutions is exon 10 (Arg399Gln). This study aimed to investigate the association between Arg399Gln SNP and the risk of squamous cell carcinoma of the head and neck. Materials and Methods:Ninety nine patients with squamous cell carcinomas of the head and neck and 89 healthy adult controls were enrolled in this study. The Arg399Gln in XRCC1 allele was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Results:In the single-locus analyses, Arg399Gln SNP showed a significant association with head and neck cancer risk (p value = 0.016 and odd ratio of 1.8). On the genotype level, we applied three analysis models, namely co-dominant, dominant, and recessive genotypes. Arg/Arg homozygous major genotype was significantly (p value <0.05) associated with head and neck squamous cell carcinoma incidence with odd ratio of 2.23 and 2.24 for the co-dominant and recessive models, respectively. Conclusion:The findings indicated that Arg399Gln allele was associated with squamous cell carcinoma of the head and neck among Jordanian patients. This allele might be used as a genetic biomarker of squamous cell carcinoma of the head and neck.

Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.

The polymorphism of XRCC1 Arg399Gln (rs25487) and male infertility risk: a meta-analysis of 1,407 cases and 974 control studies.

X-ray repair cross-complementing group 1 (XRCC1) is a scaffold protein and a key element in DNAbase excision repair process.Although, the role of XRCC1 polymorphisms in male infertility has been studied broadly, it is still a matter of debate. Hence, in order to shed light on the problem, we performed a meta-analysis to evaluate the overall effect of XRCC1 polymorphisms in male infertility risk. Databases, Web of Science, PubMed, Scopus, and Google Scholar were searched until September 15, 2018. Afterwards, the genotypes' distribution, genotyping methods, and ethnicity groups were extracted, and overall analyses were conducted. A total number of five researches on 1,407 subjects and 974 controls were found to meet our criteria in this meta-analysis. The XRCC1Arg399Gln (rs25487)polymorphism was analyzed. This is the first meta-analysis to investigate the association of XRCC1 polymorphisms (codon 399) and male infertility risk. Our results indicated that the XRCC1 Arg399Gln polymorphism was not associated with male infertility risk in the total studied populations (Tab. 2, Fig. 3, Ref. 26). Keywords: meta-analysis; male infertility; polymorphism; XRCC1 Arg399Gln.

The association of XRCC1 polymorphism with osteosarcoma risk, clinicopathologic features, and prognosis in a Chinese Han population

IntroductionThe association of single-nucleotide polymorphisms at X-ray repair cross-complementing group-1 (XRCC1) with osteosarcoma (OS) development has not been fully clear to date. The aim of the present study is to evaluate the association of XRCC1 polymorphisms with risk, clinicopathologic features, and prognosis in Chinese OS patients.MethodsA total of 146 patients with primary OS and 248 age- and gender-matched controls were included in the present study. The frequencies of four XRCC1 polymorphisms (rs25487, rs1799782, rs25489, and rs3213245) were determined between OS patients and controls. The association of XRCC1 polymorphism with clinicopathologic characteristics, prognosis, and XRCC1 expression was further evaluated.ResultsCompared with TT genotype, individuals carrying the minor C allele (TC+ CC) of rs3213245 had significantly increased risk of OS development (OR =1.83, 95% CI 1.14–3.00). OS patients carrying TC genotype and C allele at rs3213245 were more likely to be with larger tumor size and metastasis. Survival analysis demonstrated that OS patients carrying C allele (TC + CC) at rs3213245 had shorter survival time than those with TT genotype. The T to C substitution at rs3213245 could decrease XRCC1 gene transcriptional activity in vitro. XRCC1 mRNA and protein expression levels were lower in OS patients carrying TC or CC genotype at rs3213245. Besides, no significant association of rs25487, rs1799782, and rs25489 with OS was observed.ConclusionIn conclusion, these findings revealed that XRCC1 rs3213245 polymorphism was associated with increased risk of OS, which could affect XRCC1 expression in vitro and in vivo.

Association between Polymorphisms of X-Ray Repair Cross Complementing Group 1 Gene and Pancreatic Cancer Risk: a Systematic Review with Meta-Analysis

Emerging evidences have shown that common genetic polymorphisms in X-ray repair cross complementing group 1 (XRCC1) gene may be associated with the development of pancreatic cancer, but individually published studies and previous meta-analyses revealed inconclusive results. The aim of our study was to investigate the association between polymorphisms in XRCC1 gene and pancreatic cancer risk. We conducted a search of PubMed, Embase, the Cochrane Library and Web of Science databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined as measures of the strength of association between polymorphisms of XRCC1 and pancreatic cancer risk. Sensitivity analysis and publication bias were evaluated. All analyses were undertaken using the STATA 13.0. A total of 10 studies were included in this systematic review. Five common functional single-nucleotide polymorphisms (SNPs) in XRCC1 gene were found, including Arg399Gln G > A (rs25487), Arg194Trp C > T (rs1799782), Arg280His G > A (rs25489), c.1517G > C, c.1471G > A. Results from our stratified analysis based on Hardy-Weinberg equilibrium (HWE) showed that there was a robust significant association between Arg280His polymorphism and pancreatic cancer risk (allelic model, OR 0.743, 95% CI 0.576–0.958, P = 0.022; heterozygous model, OR 0.701, 95% CI 0.525–0.936, P = 0.016; dominant model, OR 0.710, 95% CI 0.537–0.939, P = 0.016). We also found a statistically significant association between c.1517G > C polymorphism and pancreatic cancer risk (Allelic model, OR 1.252, 95% CI 1.064–1.473, P = 0.007). No significant results were obtained for Arg399Gln, Arg194Trp and c.1471G > A polymorphisms. The present meta-analysis suggested that Arg280His and c.1517G > C polymorphisms in XRCC1 gene were associated with pancreatic cancer risk.

Polymorphisms of DNA repair genes XRCC1 and LIG4 and idiopathic male infertility

ABSTRACTSperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (OR, 3.12; 95% CI, 1.803-5.407). The LIG4 TT genotype carriers had decreased progressive motile sperm (p<0.05) and increased non-progressive motile sperm (p<0.001) compared with the CC genotype. Moreover, sperm concentration in subjects carrying the CT genotype was lower than that observed in CC carriers (p<0.05). The results revealed that the GG/CT and GA/CT combinations of genotypes increase the risk of infertility 3.5 and fourfold, respectively (p=0.021 and 0.004, respectively). This study demonstrated that there was an association between LIG4 Thr9Ile polymorphism and male infertility and suggests CT genotype as a risk factor for male infertility.

Association of Arg194Trp and Arg399Gln Polymorphisms of XRCC1 Gene and Risk of Differentiated Thyroid Carcinoma in Iranian-Azeri Patients

Background: The thyroid cancer (TC) is one of endocrine malignancies which contributes to more than 50% of all deaths from endocrine cancers. Gene polymorphisms including DNA repair genes such as XRCC1 (X-ray repair cross-complementing group 1) gene are thought to modify DNA repair capacity and relate to cancer risk. Objectives: The aim of the study was to detect the association between XRCC1 polymorphisms and increased risk of thyroid carcinoma among Iranian-Azeri patients. Methods: This case-control study was performed on 114 differentiated thyroid carcinoma patients and 91 normal control subjects. Single nucleotide polymorphisms (SNPs) of 194 C > T and 399 G > A of XRCC1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: In the present study, polymorphism at codon 194 of the XRCC1 gene was not found in case and control groups (P = NC (not calculated). All of the case and control subjects were 194C/C. Unlike 399 G > A genotype (P A genotype could be used as a useful molecular biomarker to predict genetic susceptibility for differentiated thyroid carcinoma in Iranian-Azeri patients.

Association between polymorphisms in DNA repair gene XRCC1 and non-melanoma skin cancer risk: a meta-analysis.

ObjectiveNon-melanoma skin cancer (NMSC) is the most common malignancy with annually rising incidence. The aim of this study was to estimate the association between three coding polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) of the DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) and NMSC susceptibility.MethodsOnline databases were searched to retrieve case–control studies published between January 2000 and November 2016. Pooled odds ratio (OR) and 95% confidence interval (CI) were employed to assess the strength of association. Overall, 10 relevant studies were finally included for analysis, including 3,143 NMSC patients and 3,540 controls. For each polymorphism of XRCC1 gene, there were 3,050 cases and 3,463 controls for Arg399Gln, 914 cases and 1,182 controls for Arg194Trp, and 279 cases and 413 controls for Arg280His.ResultsOur results showed that these three polymorphisms in the XRCC1 coding region were not associated with increased risk of NMSC in the total studied population. However, subgroup analysis by ethnicities demonstrated that Gln/Arg genotype of Arg399Gln polymorphism was associated with increased risk of NMSC under the heterogeneous model in Asian populations (Gln/Arg vs Arg/Arg: OR =1.39, 95% CI =1.04–1.87, P=0.03); subgroup analysis by tumor types showed that Trp/Trp genotype of Arg194Trp was positively associated with decreased cancer risk in squamous-cell skin cancer (SCC) type under the homogeneous model (Trp/Trp vs Arg/Arg: OR =0.38, 95% CI =0.16–0.92, P=0.03).ConclusionOur results suggested that Arg399Gln variant of XRCC1 gene might be a risk factor for NMSC in Asian populations, and Arg194Trp variant of XRCC1 gene might be a protective factor for patients with SCC. In addition, future case–control studies are still needed to further evaluate the effect of XRCC1 polymorphisms in NMSC risk.

Association and Intragenic Single-Nucleotide Polymorphism Interactions of the XRCC1 Polymorphisms for Pancreatic Cancer Susceptibility.

X-ray repair cross-complementing group 1 (XRCC1) gene is an important candidate gene for influencing human cancer risks. This study examined the main and interactive effect of 9 single-nucleotide polymorphisms (SNPs) (Arg194Trp, Arg280His, Arg399Gln, c.1254C>T, c.1517G>C, c.1471G>A, C310T, 539del542, and T1915C) of XRCC1 in contribution to pancreatic cancer (PC). A total of 298 PC patients and 298 healthy controls were enrolled. Selected SNPs in XRCC1 were genotyped. The generalized multifactor dimensionality reduction method investigated gene-gene interactions. Single-locus analyses showed that, in the codominant model, the GO genotype of 539del542 might have a higher risk for PC (odds ratio [OR], 1.47; 95% confidence interval [95% CI], 1.05-2.08). For T1915C polymorphism, the TC and CC genotypes both had a higher risk for PC (OR, 1.76; 95% CI, 1.25-2.48; OR, 1.83; 95% CI, 1.05-3.19, respectively); and a similar result was observed in the dominant model (OR, 1.77; 95% CI, 1.28-2.46). A tendency of association between Arg280His and PC was also detected in the dominant model (OR, 0.70; 95% CI, 0.48-1.00). Furthermore, the generalized multifactor dimensionality reduction method showed that the 4-locus model was significant, involving Arg280His, 539del542, T1915C, and c.1517G>C (P < 0.05). Thus, XRCC1 polymorphisms may contribute to the risk of PC independently or in an interactive manner.

Association of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in Egyptian patients

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous studies indicated that the DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two XRCC1 (X-ray repair cross-complementing group 1) (rs25487 and rs25489) gene polymorphisms and two OGG1 (8-oxoguanine glycosylase 1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 320 Egyptians individuals (160 RA patients and 160 controls). Genotyping was performed using restriction fragment length polymorphism polymerase chain reaction. We found an association between variant XRCC1 (rs25487 and rs25489) genotype polymorphisms, OGG1 (rs3219008) genotype polymorphism, and RA disease susceptibility. Moreover, the presence of the Gln/Gln, Arg/His, and His/His genotypes of XRCC1 was significantly more likely to have bone erosion and extra-articular features in RA patients. Further, patient's carrying the OGG1 A/G and G/G genotypes more likely to have bone erosion. However, the AA genotype and A allele were significantly more likely to have extra-articular features. Also, there were no significant associations between C/T OGG1 gene polymorphism and RA susceptibility, bone erosion, and extra-articular features occurrence in RA patients. We concluded that the XRCC1-Arg/Gln, XRCC1-Arg/His, and OGG1 A/G polymorphism have a role in the development of rheumatoid arthritis disease. Also, these variant are associated with the severity of RA.

Association between x-ray repair cross-complementing group 3 (XRCC3) genetic polymorphisms and papillary thyroid cancer susceptibility in a Chinese Han population

Papillary thyroid cancer (PTC) is a predominant type of thyroid cancer. Ionizing radiation is the only well-established risk factor and may result in double-strand breaks. The x-ray repair cross-complementing group 3 (XRCC3) gene plays a vital role in DNA repair through homologous recombination. We aimed at investigating the association between XRCC3 genetic polymorphisms and PTC susceptibility. Eighty-three PTC patients and 367 controls in a Chinese population were enrolled in the study. Tag single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of XRCC3 SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 SNPs and PTC susceptibility. The statistical analyses were conducted by using SPSS 13.0 software. Four tag-SNPs were initially identified by HaploView 4.2 software. Only one SNP (rs861539) was shown to be significantly associated with increased risk of PTC. There was a significant difference in smoking and drinking status between PTC cases and controls. And the stratified analysis suggested that the polymorphisms of rs861539 in XRCC3 were correlated with PTC risk in the four subgroups of smokers (ex-smokers included), non-smokers, drinkers (ex-drinkers included), and non-drinkers. The meta-analysis showed that only two studies reported a significant association between XRCC3 polymorphisms and PTC risk. In this study, we find a significant association between rs861539 polymorphisms and PTC susceptibility. However, there were inconsistent results in previous published studies. Therefore, further studies in a large population are required to gain insights into the PTC risk conferred by XRCC3 SNPs.

Abstract 3857: The polymorphisms of XRCC1 Arg194Trp and the XRCC1Arg399Gln affect the clinical features and the prognosis of MDS

Abstract Background: X-ray repair cross-complementing group 1 (XRCC1) is involved an important role in base excision repair (BER) system of DNA repair. Polymorphism in DNA repair genes may be modified of DNA repair capacity. However, it is unclear that the polymorphisms of XRCC1alter the clinical features of MDS patients. Our study was performed to evaluate the effect of the XRCC1Arg194Trp and the XRCC1Arg399Gln with the susceptibility and clinical features of MDS. Methods: We genotyped the polymorphisms by using polymerase chain reaction -restriction fragment-length polymorphism (PCR-RFLP) analysis in 119 patients with MDS [median 67.9 years, range 17.1-86.5 years; male/female 81/38; RCUD (n = 40), RARS (n = 6), RCMD (n = 21), MDS-U (n = 13), RAEB-1(n = 14), RAEB-2 (n = 12), others (n = 13)] and 202-health controls. Results: In the allele and genotype frequencies of the XRCC1Arg194Trp and the XRCC1Arg399Gln were not statistically significant difference in patients and the controls. However, Arg/Arg genotypes of XRCC1 194 and the XRCC1 399 were significantly associated with lower Hb. In addition, XRCC1 399 non Arg/Arg genotype was significantly associated with previous history of radiotherapy and multiple cancers. Furthermore, XRCC1Arg194Trp non Arg/Arg genotype and XRCC1Arg399Gln Arg/Arg genotype were significantly associated with poor prognosis of MDS patients. Conclusion: We found that the polymorphisms of XRCC1 may be affected the clinical features and the prognosis of MDS. Citation Format: Batchimeg Norjmaa, Takayuki Saitoh, Tetsuhiro Kasamatsu, Yusuke Minato, Noriaki Sunaga, Hirokazu Murakami. The polymorphisms of XRCC1 Arg194Trp and the XRCC1Arg399Gln affect the clinical features and the prognosis of MDS. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3857. doi:10.1158/1538-7445.AM2015-3857

Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31–3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97–1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49–3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02–1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26–0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results.

Clinical outcome of cisplatin-based chemotherapy is associated with the polymorphisms of GSTP1 and XRCC1 in advanced non-small cell lung cancer patients.

This study is to evaluate the association of polymorphisms of glutathione S-transferase P1 (GSTP1), copper-transporting P-type adenosine triphosphatase A (ATP7A) and X-ray repair cross-complementing group 1 (XRCC1) with the efficacy and toxicity of cisplatin-based treatment in advanced non-small cell lung cancer (NSCLC) patients. The outcomes of 97 advanced non-small cell lung cancer patients treated with cisplatin-based chemotherapy were estimated. GSTP1, ATP7A, and XRCC1 genetic polymorphisms were determined via polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Association of the polymorphisms with the efficacy and toxicity of cisplatin was analyzed, respectively. Significant associations were observed between GSTP1 A313G and response rate (RR) (p=0.027), disease control rate (DCR) (p=0.019), and progression-free survival (PFS) (p=0.044), respectively. Patients with AG and GG of GSTP1 have notably lower risk of anemia (p=0.046). XRCC1 A1196G was associated with the incidence of lymphopenia (p=0.024) and diarrhea (p=0.020). ATP7A C2299G was not related with RR, DCR, PFS, and the risk of toxicity. Advanced NSCLC patients with AA genotype of GSTP1 would obtain better curative effect followed with more risk of anemia when treated by cisplatin-based chemotherapy. ATP7A C2299G does not impact the efficacy and toxicity of cisplatin-based chemotherapy. XRCC1 1196A allele could predict the incidence of lymphopenia and diarrhea.

XRCC1 genetic polymorphism acts a potential biomarker for lung cancer

Lung cancer is one of the most common but serious cancers in the world. Both the X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug resistance 1 (MDR1) gene are important candidate genes influencing the susceptibility to various diseases, including lung cancer. This study aimed to assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the susceptibility to lung cancer. In this study, a total of 320 lung cancer patients and 346 cancer-free controls in Chinese population were enrolled in this study. Data about the clinical characteristics and related risk factors of lung cancer were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain reaction method. Our data showed that the risk for lung cancer increased significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G > A, rs25487) of XRCC1, but there are no significant differences in the allelic and genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer patients and cancer-free controls. In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.

Polymorphisms in DNA repair genes XRCC1 and XRCC3, occupational exposure to arsenic and sunlight, and the risk of non-melanoma skin cancer in a European case-control study

X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3) polymorphisms are relatively frequent in Caucasian populations and may have implications in skin cancer modulation. A few studies have evaluated their association with non-melanoma skin cancer (NMSC), but the results are inconsistent. In the current study, we aim to assess the impact of XRCC1 R399Q and XRCC3 T241M polymorphisms on the risk of NMSC associated with sunlight and arsenic exposure. Study participants consist of 618 new cases of NMSC and 527 hospital-based controls frequency matched on age, sex, and county of residence from Hungary, Romania, and Slovakia. Adjusted effects are estimated using multivariable logistic regression. The results indicate an increased risk of squamous cell carcinoma (SCC) for the homozygous variant genotype of XRCC1 R399Q (OR 2.53, 95% CI 1.14–5.65) and a protective effect against basal cell carcinoma (BCC) for the homozygous variant genotype of XRCC3 T241M (OR 0.61, 95% CI 0.41–0.92), compared with the respective homozygous common genotypes. Significant interactions are detected between XRCC3 T241M and sunlight exposure at work, and between XRCC3 T241M and exposure to arsenic in drinking water (p-value for interaction <0.10). In conclusion, the current study demonstrates that polymorphisms in XRCC genes may modify the associations between skin cancer risk and exposure to sunlight or arsenic. Given the high prevalence of genetic polymorphisms modifying the association between exposure to environmental carcinogens and NMSC, these results are of substantial relevance to public health.

No association between XRCC1 genetic polymorphisms and differentiated thyroid carcinoma risk: a meta-analysis.

The X-ray repair cross-complementing group 1 (XRCC1) gene belongs to the family of DNA repair genes. Polymorphisms in the XRCC1 gene, Arg399Gln, Arg194Trp and Arg280His, have been reported to have implications in differentiated thyroid carcinoma (DTC) susceptibility, but the results remain conflicting and no meta-analysis has been published. Therefore, we carried out a systematic review of the published epidemiology studies, aiming to assess the relationship between XRCC1 polymorphisms and susceptibility to DTC risk. We selected three databases, PubMed, EMBASE and CNKI, in which to search for published literature. With respect to DTC risk associated with XRCC1, combined odds ratios (ORs) and 95% confidence intervals (CI) were appropriately calculated on the basis of co-dominant, dominant and recessive models. To investigate different effects from specific race, subgroup analyses were carried out in Asian and Caucasian populations. Eight studies meeting the inclusion criteria were eventually selected for Arg399Gln (1,550 cases and 2,692 controls), five studies for Arg194Trp (858 cases and 1,394 controls) and five studies for Arg280His (1,237 cases and 2,267 controls). The combined results of the relevant studies exhibited that no significant associations with DTC risk were demonstrated for polymorphisms in XRCC1 Arg399Gln, Arg194Trp and Arg280His in all genetic models. Stratified analyses in Asian and Caucasian populations showed similar results. This meta-analysis arrives at a conclusion that the XRCC1 (Arg399Gln, Arg194Trp, Arg280His) polymorphisms appear to confer no risk for DTC.