XRCC1 codon 399 and ERCC2 codon 751 polymorphism, smoking, and drinking and risk of esophageal squamous cell carcinoma in a North Indian population

XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementing group 2) codon 751 polymorphisms were studied in esophageal squamous cell carcinoma (ESQCC) in a North Indian population. Peripheral blood samples of 120 cases and 160 age-and-gender matching controls were collected from North India and the two polymorphisms were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques. The data were analyzed with a logistic regression model. The XRCC1 codon 399 Gln/Gln genotype was significantly associated with reduced risk of ESQCC (OR = 0.31, 95% CI = 0.12-0.78, P = 0.01). In smokers, the XRCC1 Arg/Gln genotype was marginally and statistically nonsignificantly (OR = 1.5) associated with increased risk of this cancer. In drinkers, the XRCC1 Gln/Gln genotype was significantly protective (OR = 0.06, 95% CI = 0.007-0.605, P = 0.03), whereas ERCC2 (Lys/Gln-Gln/Gln) was marginally associated with increased risk (OR = 2.1, 95% CI = 0.46-9.44). Upon analysis of gene-gene interaction, a relationship was observed, although statistically nonsignificant, between combined genotypes of XRCC1 (Arg/Gln-Gln/Gln)-ERCC2 Gln/Gln (OR = 0.33, 95% CI = 0.09-1.16) and XRCC1 (Gln/Gln)-ERCC2 (Lys/Gln) (OR = 0.36, 95% CI = 0.11-1.17) and reduced risk of ESQCC in the North Indian population. These observations suggest that the Gln/Gln genotype of XRCC1 might play an important role in DNA repair in ESQCC.     

DNA repair gene XRCC1 Arg399Gln polymorphism is associated with increased risk of uterine leiomyoma

BACKGROUND: DNA repair gene XRCC1 Arg399Gln polymorphism has been associated with the risk of several human tumours. In the present study we investigated whether the XRCC1 polymorphism is related to the risk of uterine leiomyoma, the most common neoplasm of the female genital tract. METHODS: Three hundred and twenty-seven patients with uterine leiomyoma and 197 normal controls were enrolled, and XRCC1 genotyping was determined by PCR and restriction fragment length polymorphism. RESULTS: The proportions of individuals homozygous for 399Arg allele, heterozygous and homozygous for the 399Gln allele were 85.8%, 13.7% and 0.5% among the control group, and 46.2%, 53.2% and 0.6% in those with leiomyoma (P < 0.001), respectively. Logistic regression analysis (after adjusting for age, parity, menarche age and body mass index) showed a significant increased risk of uterine leiomyoma in women with the Arg/Gln genotype versus the Arg/Arg genotype (odds ratio 6.79; 95% confidence interval 4.20-10.99; P < 0.001). CONCLUSIONS: In Korean women, the 399Gln polymorphism of XRCC1 is associated with an increased risk of uterine leiomyoma.     

Assoication of XRCC1 gene polymorphisms with risk of non-small cell lung cancer

DNA repair genes is a key factor for cancer susceptibility, and we conducted a case-control study to investigate the association of XRCC1 codons 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln) with risk of NSCLC. 210 NSCLC patients and 210 health control subjects were randomly selected from Huaihe Hospital between January 2012 and June 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to assess the genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln. By multivariate logistic regression analysis, we found individuals carrying with Trp/Trp and Arg/Trp + Trp/Trp genotypes were associated with a significantly increased risk of NSCLC compared with Arg/Arg genotype, and the OR (95% CI) were 3.15 (1.32-8.09) and 1.52 (1.02-2.28), respectively. The potential association of Arg/Trp+ Trp/Trp genotype of XRCC1 Arg194Trp with the risk of NSCLC is more evidence in smokers, and the OR (95% CI) was 1.78 (1.01-3.24). In conclusion, we found that XRCC1 Arg194Trp polymorphism may be associated with NSCLC risk, especially in smokers.     

Interaction between Polymorphisms of DNA Repair Genes Significantly Modulated Bladder Cancer Risk

DNA repair is a primary defense mechanism against damage caused by exogenous and endogenous sources. We examined the associations between bladder cancer and 7 polymorphisms from 5 genes involved in the maintenance of genetic stability (MMR: MLH1-93G>A; BER: XRCC1--77T>C and Arg399Gln; NER:XPC Lys939Gln and PAT +/-; DSBR:ATM G5557A and XRCC7 G6721T) in 302 incident bladder cancer cases and 311 hospital controls. Genotyping was done using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The homozygous variant of XRCC7 G6721T (Odds Ratio [OR]: 2.36; 95% Confidence Interval [CI]: 1.13-4.92) was associated with increased bladder cancer risk. In an analysis of combined genotypes, the combination of XRCC1Arg399Gln (Gln allele) with XRCC1-77 T/T led to an increase in risk (OR: 1.61; 95% CI: 1.10-2.36). Moreover, when the XPCLys939Gln (Gln allele) (nucleotide excision repair [NER]) was present together with XRCC7 (T allele) (double strand break repair [DSBR]), the bladder cancer risk dramatically increased (OR: 4.42; 95% CI: 1.23-15.87). Our results suggest that there are multigenic variations in the DNA repair pathway involved in bladder cancer susceptibility, despite the existence of ethnic group differences.     

DNA repair gene XRCC1 and XPD polymorphisms and the risk of idiopathic azoospermia in a Chinese population

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity and further influence the risk of developing cancer. However, little information is available on these polymorphisms in infertility. To investigate whether polymorphisms in DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD), alone or in combination, are associated with the risk of developing idiopathic azoospermia, the genotype and allele frequencies of three observed polymorphisms (XRCC1 Arg194Trp and Arg399Gln, and XPD Lys751Gln) were examined by polymerase chain reaction-restriction fragment length polymorphism based on a Chinese population consisting of 171 idiopathic azoospermia patients and 247 normal-spermatogenesis fertile controls. Associations between the polymorphisms and the idiopathic azoospermia risk were estimated by logistic regression, and the Statistical analysis system was used to test the gene-gene joint effects. All observed polymorphisms were in agreement with Hardy-Weinberg equilibrium. The XPD 751Gln allele seemed to be a risk allele for azoospermia, with a frequency of 11.40% in the cases and 5.67% in the controls (p=0.004). Compared with the Lys/Lys genotype, the XPD 751 Lys/ increased 5.100- or 3.064-fold, respectively, when combined with the XRCC1 194 Arg/Arg or 399 Arg/Arg genotype. In conclusion, our study provided the first evidence that the XPD and XRCC1 polymorphisms contributed to the risk of developing idiopathic azoospermia in a selected Chinese population.     

XRCC1 polymorphism and lung cancer risk in relation to tobacco smoking

DNA repair plays a critical role in protecting the genome of the cell from carcinogens or ionising radiation. Reduced DNA-repair capacity can increase susceptibility to occupational-induced cancer. Three coding polymorphisms at codons 194, 280, and 399 in X-ray cross complementing group 1 (XRCC1) DNA-repair gene have been identified, and it is possible that these polymorphisms may affect DNA- repair capacity and thus modulate cancer susceptibility. In the current German study, we investigated the role of XRCC1-polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes, especially in relation to tobacco smoking. Three polymorphisms; XRCC1 Arg194Trp, XRCC1 Arg280His and XRCC1 Arg399Gln, were determined by real-time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients who carried at least one mutant variant allele of XRCC1 Arg194Trp (OR=1.03; 95%-CI: 0.66-1.61), XRCC1 Arg280His (OR=0.95; 95%-CI: 0.57-1.60), or XRCC1 Arg399Gln (OR=0.99 CI: 0.73-1.34), did not show any elevated risks. When analysed by histology, no individual subtype of lung cancer was significantly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption. Stratified analysis between tobacco smoking and variant genotypes revealed increasing risks for heavy smokers (>60 pack-years), with the presence of at least one copy of the XRCC1 Arg194Trp variant allele (OR=79.29; 95%-CI: 8.53-737.04) and the XRCC1 Arg399Gln (OR=61.87; 95%-CI: 15.65-244.67). By analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study, the XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln-polymorphisms, had no relevant modifying effect on lung cancer risk and cumulative smoking dose.     

Single nucleotide polymorphisms in base-excision repair genes hOGG1, APE1 and XRCC1 do not alter risk of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a poorly understood etiology. There is considerable evidence that oxidative stress occurs in AD and increased DNA damage has been found in brain tissues and leukocytes of AD patients. Base excision repair (BER) is the major pathway responsible for removing oxidative DNA damage. Polymorphisms in DNA-repair genes have been associated with the increased risk of several age-related disorders including various types of cancer and could also be related to the etiology of AD. We conducted a case-control study including 91 patients with AD and age- and sex-matched 93 control subjects to examine the role of single nucleotide polymorphisms of BER genes, hOGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC1 (Arg280His and Arg399Gln) as a risk factor for AD. The frequencies of the hOGG1-Ser326Cys, APE1-Asp148Glu and XRCC1-Arg280His and XRCC1-Arg399Gln variant alleles in our control group were 0.23, 0.31, 0.10 and 0.33, respectively. No significant association was observed between the variant alleles of hOGG1-Ser326Cys (OR=1.32, 95% CI=0.83-2.11), APE1-Asp148Glu (OR=1.08, 95% CI=0.70-1.68), XRCC1-Arg280His (OR=0.53, 95% CI=0.24-1.14) and XRCC1-Arg399Gln (OR=1.05, 95% CI=0.68-1.63) and AD. Our results suggest that the polymorphic variants of these BER genes are not independent risk factors for AD.     

XRCC1 polymorphisms and risk of papillary thyroid carcinoma in a Korean sample

Polymorphisms of DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1) might contribute to individual susceptibility to different types of cancers. We analyzed the relationship between XRCC1 polymorphisms and the risk of papillary thyroid carcinoma in a Korean sample. A hospital-based case-control study was performed in 111 papillary thyroid carcinoma patients and 100 normal control subjects. XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The XRCC1 Arg194Trp Arg/Trp genotype was significantly associated with a decreased risk of papillary thyroid carcinoma compared to that of Arg/Arg genotype (odds ratio [95% confidence intervals]; 0.550 [0.308-0.983]). There was no significant association between XRCC1 Arg399Gln genotypes and risk of papillary thyroid carcinoma. Based on these results, the XRCC1 Arg194Trp Arg/Trp genotype could be used as a useful molecular biomarker to predict genetic susceptibility for papillary thyroid carcinoma in Koreans.     

Detection of XRCC1 gene polymorphisms in Egyptian patients with acute myeloid leukemia

XRCC1 is a polymorphic gene belonging to one of the major deoxyribonucleic acid (DNA) repair pathways. XRCC1 is involved in base excision repair (BER) and the repair of single-strand breaks. Several variants of XRCC1 have been described, including one affecting codon 399 in exon 10 that results in an arginine (Arg) to glutamine (Gln) substitution and one affecting codon 194 in exon 6 that results in an Arg to tryptophan (Trp) substitution. The aim of this study was to determine the presence of these polymorphisms in the Egyptian population and to define their role in modulating susceptibility to development of acute myeloblastic leukemia (AML) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 40 de novo AML patients and 20 controls. The risk of development of AML was found to be significantly increased when variant XRCC1-399 (Arg/Gln) is present (P value 0.025). Moreover, the risk of AML development was found to be significantly increased when variant XRCC1-194 (Arg/Trp) is present (P value 0.002), whereas the risk of AML development is even higher when both variants XRCC1-Arg-399 Gln and Arg-194 Trp alleles are present (odds ratio [OR] 6.15 and 4.00 and 95% CI 1.88–20.05 and 1.13–14.08, respectively), presumably because an increase in DNA damage significantly increases the risk of development of AML, and the phenotypes, as a result, interact to increase this risk. These results strongly suggest that BER pathway, notably XRCC1, is important in the pathogenesis of de novo AML.     

Polymorphisms in DNA repair genes as risk factors for spina bifida and orofacial clefts

Repairing DNA damage is critical during embryogenesis because development involves sensitive periods of cell proliferation, and abnormal cell growth or death can result in malformations. Knockout mouse experiments have demonstrated that disruption of DNA repair genes results in embryolethality and structural defects. Studies using mid-organogenesis rat embryos showed that DNA repair genes were variably expressed. It is hypothesized that polymorphisms that alter the functionality of DNA repair enzymes may modify the risk of malformations. We conducted a case-control analysis to investigate the relationship between DNA repair gene polymorphisms and the risk of spina bifida and oral clefts. Newborn screening blood spot DNA was obtained for 250 cases (125 spina bifida, 125 oral clefts) identified by the California Birth Defects Monitoring Program, and 350 non-malformation controls identified from birth records. Six single nucleotide polymorphisms of five DNA repair genes representing three distinct repair pathways were interrogated including: XRCC1 (Arg399Gln), APE1 (Asp148Glu), XRCC3 (Thr241Met), hOGG1(Ser326Cys), XPD (Asp312Asn, Lys751Gln). Elevated or decreased odds ratios (OR, adjusted for race/ethnicity) for spina bifida were found for genotypes containing at least one copy of the variant allele for XPD [751Gln, OR = 1.62; 95% confidence interval (CI) = 1.05-2.50] and APE 148 (OR = 0.58; CI = 0.37-0.90). A decreased risk of oral clefts was found for XRCC3 (OR = 0.62; CI = 0.39-0.99) and hOGG1 (326 Cys/Cys, OR = 0.22; CI = 0.06-0.78). This study suggested that polymorphisms of DNA repair genes, representing different major repair pathways, may affect risk of two major birth defects. Future, larger studies, examining additional repair genes, birth defects, and interaction with exposures are recommended.     

XRCC1、hOGG1基因多态性与喉癌遗传易感性的关系

目的 探讨X线修复交叉互补组1基因(X-ray repair cross complementing group 1,XRCC1)、8-羟基鸟嘌呤修复酶基因(human 8-oxoguanine glycosylase I,hOGG1)多态性与喉癌遗传易感性的关系.方法 采用病例-对照设计,应用聚合酶链反应-限制性片段长度多态性分析法检测了72例经病理确诊的喉癌患者和随机抽样的72例无肿瘤、无遗传病对照者XRCC1-Arg399Gln、hOGG1-Ser326Cys多态性.结果 病例组XRCC1第399位密码子杂合型(Arg/Gln)及突变型(Gln/Gln)和hOGG1第326位密码子杂合型(Ser/Cys)及突变型(Cys/Cys)分布频率均高于对照组(P＜0.05),与携带XRCC1-399野生型(Arg/Arg)、hOGG1-326野生型(Ser/Ser)个体相比,携带该基因型的个体喉癌的发病风险分别升高了3.37和2.54倍.交互作用分析显示,吸烟组与不吸烟组相比,携带XRCC1、hOGG1各基因型的个体的喉癌发病风险差异未发现存在统计学意义(xH12=0.15,xH22=0.28,P＞0.05).结论 XRCC1-399位点Arg→Gln和hOGG1-326位点Ser→Cys的氨基酸替换可能导致喉癌的发病风险增加,XRCC1-Arg399Gln、hOGG1-Ser326Cys多态性可能与喉癌的遗传易感性有关.     

Polymorphisms in the thymidylate synthase promoter and the DNA repair genes XRCC1 and XPD in a Brazilian population

Polymorphisms in genes responsible for maintaining genomic integrity are potential modifiers of disease risk. Since considerable interindividual and interethnic variation in DNA repair capacity has been associated with polymorphic alleles, we evaluated the frequency of the 2R/3R variants in the TS promoter, Arg194Trp and Arg399Gln in the XRCC1 gene, and Asp312Asn and Lys751Gln in the XPD gene in 364 healthy individuals from a Brazilian population separated by ethnicity (European ancestry and African ancestry). The genotypes were determined by PCR (TS) or by PCR-RFLP (XRCC1 and XPD). The frequency of the TS 3R allele was 0.56 for whites and 0.51 for nonwhites. In the case of the XRCC1 MspI polymorphism, the allele frequencies were 0.09 for 194Trp in both nonwhites and whites and 0.27 and 0.28 for 399Gln in nonwhites and whites, respectively. For the XPD 312Asn allele, we found a frequency of 0.25 in white individuals, which was significantly different (P = 0.025) from that seen in nonwhites (0.15). Similarly, the 751Gln polymorphic allele of the XPD gene was significantly more frequent (P < 0.002) in whites (0.30) than in nonwhites (0.20). The genotype frequencies were within Hardy-Weinberg equilibrium. We concluded that the genotype and allele frequencies of XPD gene polymorphism differed between white and nonwhite Brazilians, and that the frequencies of the XPD 312Asn and XRCC1 399Gln alleles in this Brazilian population showed ethnic variability when compared with those observed in other populations.     

Genetic regulation of ionizing radiation sensitivity and breast cancer risk

Genetic variability in DNA repair may contribute to hypersensitivity to ionizing radiation (IR) and susceptibility to breast cancer. We used samples collected from a clinic-based breast cancer case-control study to test the working hypothesis that amino acid substitution variants of DNA repair genes may contribute to prolonged cell-cycle delay following IR and breast cancer risk. Fluorescence-activated cell sorter (FACS) analysis was used to measure cell-cycle delay. PCR-restriction fragment length polymorphism (RFLP) assays were used to determine four genotypes of three DNA repair genes: XRCC1, 194 Arg/Trp and 399 Arg/Gln; XRCC3, 241 Thr/Met; and APE1, 148 Asp/Glu. The data showed that breast cancer patients had a significantly higher delay index than that of controls (P < 0.001); the means +/- SD for cases and controls were 36.0 +/- 13.1 (n = 118) and 31.4 +/- 11.5 (n = 225), respectively. There was a significant dose-response relationship between delay index, categorized into quartiles, and an increasing risk of breast cancer (crude odds ratios: 1.00, 1.00, 1.27, and 2.46, respectively; P(trend) = 0.002). In controls, prolonged cell-cycle delay was significantly associated with the number of variant alleles in APE1 Asp148Glu and XRCC1 Arg399Gln genotypes (P(trend) = 0.001). Although larger studies are needed to validate the results, our data suggest that an inherited hypersensitivity to IR may contribute to human breast carcinogenesis.     

原发性肝细胞癌与X线修复交叉互补基因1遗传位点的相关研究

目的研究X线修复交叉互补基因1(XRCC1)遗传位点399多态性对中国人群原发性肝细胞癌的相关性。方法通过检索PubMed和CNKI等数据库,收集有关XRCC1多态性与原发性肝细胞癌关联的6篇相互独立研究文献,对1072原发肝癌病例和1400健康人进行Meta分析和关联研究。结果通过XRCC1 399位点所有数据研究,经等位基因病例对照,等位基因G的OR值(95%CI)为1.23(0.96,1.59),=0.11;与基因型AA比较,基因型AG+GG的OR值(95%CI)为1.33(0.92,1.92),=0.13,说明该位点多态性对原发性肝癌发生不是危险因子。通过层次分析,在乙肝或黄曲霉素暴露所诱导的那80%的肝癌患者中,该位点是原发性肝癌发生的危险因子在未知病因所诱导的肝癌患者中,该位点未显示对原发性肝癌发生危险作用。结论中国人群XRCC1基因遗传位点399与乙肝或黄曲霉素暴露所诱导的肝癌发生相关。     

Influence of DNA repair gene polymorphisms on the initial repair of MMS-induced DNA damage in human lymphocytes as measured by the alkaline comet assay

We have applied the alkaline comet assay to study the functional impact of gene polymorphisms in base excision repair (APEX1 Asp148Glu, XRCC1 Arg194Trp, XRCC1 Arg399Gln) and homologous recombination repair (XRCC3 Thr241Met, NBS1 Glu185Gln), two pathways that play crucial roles in the repair of DNA damage induced by methylmethane sulphonate (MMS). We also examined the effect of polymorphisms in mismatch repair (MLH1 -93 A/G) and nucleotide excision repair (XPD Lys751Gln) as putative negative controls based on the limited roles of these pathways in MMS-induced repair. Phytohemagglutinin-stimulated peripheral lymphocytes from 52 healthy individuals were treated with MMS and allowed to repair for 0, 15, 40, or 120 min after a 6-min washing step. DNA damage was measured as a pseudo-percentage score (comparable to % tail DNA) converted from a total visual score calculated from the distribution of cells with different degrees of damage (normal, mild, moderate and severe). The repair was faster at the beginning of the observation period than towards the end, and was not complete after 2 hr. Presence of the APEX1 148Asp, XRCC3 241Met or NBS1 185Gln alleles were significantly associated with a high pseudo-percentage score (above median) at early time points, with the APEX1 effect being most prolonged (up to 40 min after washing, odds ratio 5.6, 95% confidence interval 2.0-15.5). No significant effects were seen with the XRCC1 Arg194Trp, XRCC1 Arg399Gln, MLH1 -93A/G and XPD Lys751Gln polymorphisms. Our results provide evidence for the functional nature of the variant alleles studied in the APEX1, XRCC3, and NBS1 genes.     

BER修复基因多态性与肺癌易感性的研究进展

碱基切除修复(base excision repair,BER)通路是DNA损伤修复的关键通路,通路中的8-羟基鸟嘌呤DNA糖苷酶基因(human 8-oxoguanine glycosylase,hOGG1),人类X线交叉互补修复基因(X-ray repair cross-complementing group 1,XRCC1),MutY homolog(MUTYH)基因的单核苷酸多态性影响BER通路中重要的酶和蛋白质的功能,导致修复障碍,最终引起癌症发生.DNA损伤修复基因单核苷酸多态性和肺癌易感性的研究结果尚存在争议,本文对近年来BER通路基因hOGG1Ser326Cys,XRCC1 Arg194Trp,XRCC1 Arg280His,XRCC1 Arg399Gln,XRCC1-77T>C和MUTYHHis324Gln多态性与肺癌易感性的关系的研究进行汇总,并探讨了多项研究对BER基因多态性与不同肺癌亚型的关系以及与吸烟之间关系.基因多态性与肺癌易感性关系受多因素影响,其相关性尚待进一步探索.     

BER修复基因多态性与肺癌易感性的研究进展

碱基切除修复(base excision repair,BER)通路是DNA损伤修复的关键通路,通路中的8-羟基鸟嘌呤DNA糖苷酶基因(human 8-oxoguanine glycosylase,hOGG1),人类X线交叉互补修复基因(X-ray repair cross-complementing group 1,XRCC1),MutY homolog(MUTYH)基因的单核苷酸多态性影响BER通路中重要的酶和蛋白质的功能,导致修复障碍,最终引起癌症发生.DNA损伤修复基因单核苷酸多态性和肺癌易感性的研究结果尚存在争议,本文对近年来BER通路基因hOGG1Ser326Cys,XRCC1 Arg194Trp,XRCC1 Arg280His,XRCC1 Arg399Gln,XRCC1-77T>C和MUTYHHis324Gln多态性与肺癌易感性的关系的研究进行汇总,并探讨了多项研究对BER基因多态性与不同肺癌亚型的关系以及与吸烟之间关系.基因多态性与肺癌易感性关系受多因素影响,其相关性尚待进一步探索.     

BER修复基因多态性与肺癌易感性的研究进展

碱基切除修复(base excision repair,BER)通路是DNA损伤修复的关键通路,通路中的8-羟基鸟嘌呤DNA糖苷酶基因(human 8-oxoguanine glycosylase,hOGG1),人类X线交叉互补修复基因(X-ray repair cross-complementing group 1,XRCC1),MutY homolog(MUTYH)基因的单核苷酸多态性影响BER通路中重要的酶和蛋白质的功能,导致修复障碍,最终引起癌症发生.DNA损伤修复基因单核苷酸多态性和肺癌易感性的研究结果尚存在争议,本文对近年来BER通路基因hOGG1Ser326Cys,XRCC1 Arg194Trp,XRCC1 Arg280His,XRCC1 Arg399Gln,XRCC1-77T>C和MUTYHHis324Gln多态性与肺癌易感性的关系的研究进行汇总,并探讨了多项研究对BER基因多态性与不同肺癌亚型的关系以及与吸烟之间关系.基因多态性与肺癌易感性关系受多因素影响,其相关性尚待进一步探索.     

Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population

Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens. Platinum agents have shown to be effective in the treatment of gastric cancer. We assessed whether single nucleotide polymorphisms (SNPs) in xeroderma pigmentosum group D (XPD), X-ray repair cross complementing group 1 (XRCC1) and glutathione S-transferase P1 (GSTP1) predicted overall survival in gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population. SNPs of XPD-751, XRCC1-399 and GSTP1-105 in 62 gastric cancer patients were evaluated using the TaqMan 5' nuclease assay. Genotypes were correlated to survival. The median overall survival time was 322 days (range: 56-2058 days). The median survival times for patients with Arg/Arg or Arg/Gln genotypes of XRCC1 gene were significantly longer than others (P=0.03). For 58 patients with ECOG PS (Eastern Cooperative Oncology Group performance status)相似文献   

Association of GSTP1 and XRCC1 gene polymorphisms with clinical outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy

We investigated the association between the clinical outcome and GSTP1 and XRCC1 gene polymorphisms in advanced NSCLC patients with cisplatin-based chemotherapy. We prospectively recruited 325 NSCLC patients between January 2010 and January 2014. Genotypes of GSTP1 A313G, XRCC1 Arg194Trp, Arg280His and Arg399Gln were conducted using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. AG and GG genotypes of GSTP1 A313G were correlated with a higher CR + PR when compared with AA genotype. Furthermore, GA and AA genotypes of XRCC1 Arg399Gln were associated with more CR + PR when compared with GG genotype. In the Cox proportional hazards model, GG genotype of GSTP1 A313G was significantly correlated with a longer median survival time when compared with AA genotype, and it is associated with a heavy decreased risk of death from NSCLC. Moreover, GA and AA genotypes of XRCC1 Arg399Gln had a significantly longer median survival time, and GA and AA genotypes were significantly associated with a moderate reduced risk of death from NSCLC. GSTP1 A313G and XRCC1 Arg399Gln gene polymorphisms might influence the response to cisplatin-based chemotherapy and affect the clinical outcome of advanced NSCLC.