Polymorphisms of DNA repair genes and risk of non-small cell lung cancer

Lung cancer is a leading cause of cancer mortality with an inter-individual difference in susceptibility to the disease. The inheritance of low-efficiency genotypes involved in DNA repair and replication may contribute to the difference in susceptibility. We investigated 44 single nucleotide polymorphisms (SNPs) in 20 DNA repair genes including nucleotide excision repair (NER) genes XPA, ERCC1, ERCC2/XPD, ERCC4/XPF and ERCC5/XPG; base excision repair (BER) genes APE1/APEX, OGG1, MPG, XRCC1, PCNA, POLB, POLiota, LIG3 and EXO1; double-strand break repair (DSB-R) genes XRCC2, XRCC3, XRCC9, NBS1 and ATR; and direct damage reversal (DR) gene MGMT/AGT. The study included 343 non-small cell lung cancer (NSCLC) cases and 413 controls from Norwegian general population. Our results indicate that SNPs in the NER genes ERCC1 (Asn118Asn, 15310G>C, 8902G>T), XPA (-4G>A), ERCC2/XPD (Lys751Gln) and ERCC5/XPD (His46His); the BER genes APE1/APEX (Ile64Val), OGG1 (Ser326Cys), PCNA (1876A>G) and XRCC1 (Arg194Trp, Arg280His, Arg399Gln); and the DSB-R genes ATR (Thr211Met), NBS1 (Glu185Gln), XRCC2 (Arg188His) and XRCC9 (Thr297Ile) modulate NSCLC risk. The level of polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adducts in normal lung tissue from 211 patients was analysed. The variant alleles of XRCC1(Arg280His), XRCC1 (Arg399Gln), ERCC1(G8092T), ERCC5(His46His) and MGMT/AGT(Lys178Arg) were more frequent in patients with PAH-DNA adduct levels lower than the mean whereas the XRCC1(Arg194Trp) variant was more frequent in cases with higher adduct levels than the mean.     

A Meta-Analysis for Association of XRCC1, XRCC2 and XRCC3 Polymorphisms with Susceptibility to Thyroid Cancer

Background: We conducted a comprehensive meta-analysis to explore the association of polymorphisms at XRCC1, XRCC2 and XRCC3 genes with susceptibility to thyroid cancer (TC). Methods: We searched PubMed, EMBASE, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results: A total of 67 studies including 17 studies with 6,806 cases and 5,229 controls on XRCC1 Arg399Gln, 13 studies with 3,234 cases and 4,807 controls on XRCC1 Arg280His, 13 studies with 2,956 cases and 3,860 controls on XRCC1 Arg194Trp, five studies with 1,287 cases and 1,422 controls on XRCC2 Arg188His, 13 studies with 2,488 cases and 3,586 controls on XRCC3 Thr241Met, and six studies with 1,828 cases and 2,060 controls on XRCC3 IVS5-14 polymorphism were selected. Polled data revealed that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His and XRCC3 Thr241Met and IVS5-14 polymorphisms were not significantly associated with an increased risk of TC. Stratified analyses by ethnicity showed that the XRCC1 Arg399Gln polymorphism was associated with TC risk in Caucasians, but not in Asians. Conclusions: Our meta-analysis indicated that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met and IVS5-14 polymorphisms were not associated with risk of TC in the global population.  Further well-designed investigations with large sample sizes are required to confirm our results.     

Genetic polymorphisms in DNA repair genes and risk of lung cancer

Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of lung cancer. The frequencies of several amino acid substitutions in XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XRCC3 (Thr241Met), XPD (Ile199Met, His201Tyr, Asp312Asn and Lys751Gln) and XPF (Pro379Ser) genes were studied in 96 non-small-cell lung cancer (NSCLC) cases and in 96 healthy controls matched for age, gender and cigarette smoking. The XPD codon 312 Asp/Asp genotype was found to have almost twice the risk of lung cancer when the Asp/Asn + Asn/Asn combined genotype served as reference [odds ratio (OR) 1.86, 95% confidence interval (CI), 1.02-3.40]. In light cigarette smokers (less than the median of 34.5 pack-years), the XPD codon 312 Asp/Asp genotype was more frequent among cases than in controls and was associated with an increased risk of NSCLC. Compared with the Asn/Asn carriers, the OR in light smokers with the Asp/Asn genotype was 1.70 (CI0.35 0.43-6.74) and the OR in those with the Asp/Asp genotype was 5.32 (CI0.35-21.02) (P trend = 0.01). The 312 Asp/Asp genotype was not associated with lung cancer risk in never-smokers or heavy smokers (>34.5 pack-years). The XPD-312Asp and -751Lys polymorphisms were in linkage disequilibrium in the group studied; this finding was further supported by pedigree analysis of four families from Utah. The XPD 312Asp amino acid is evolutionarily conserved and is located in the seven-motif helicase domain of the RecQ family of DNA helicases. Our results indicate that these polymorphisms in the XPD gene should be investigated further for the possible attenuation of DNA repair and apoptotic functions and that additional molecular epidemiological studies are warranted to extend these findings.     

XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk.

Whereas animal and in vitro studies support a role of unsaturated fatty acids in colon carcinogenesis, the epidemiologic evidence is inconclusive. Using a large sigmoidoscopy-based case-control study (753 cases and 799 controls) in Los Angeles County, we investigated possible associations between single-nucleotide polymorphisms in the XRCC1 (codons 194 Arg/Trp and codon 399 Arg/Gln) and XRCC3 (codon 241 Thr/Met) genes and colorectal adenoma risk and their possible role as modifiers of the effect of monounsaturated fatty acid, the ratio of omega-6/omega-3 polyunsaturated fatty acids, and antioxidant intake. We found no evidence of associations between the XRCC1 codon 194 Arg/Trp or Trp/Trp genotypes and the XRCC3 codon 241 Thr/Met or Met/Met genotypes. Subjects with the XRCC1 Gln/Gln genotype were inversely associated with adenoma risk (odds ratio, 0.6; 95% confidence interval, 0.4-0.9; P = 0.01) when compared with subjects with Arg/Arg and Arg/Gln genotypes combined. We found no evidence of gene-dietary fat interactions for the XRCC3 codon 241 polymorphism. However, our data suggest an XRCC1-unsaturated fat interaction. High monounsaturated fatty acid intake was associated with adenoma risk only among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln combined genotypes (P for interaction = 0.018). High omega-6/omega-3 polyunsaturated fatty acid ratios were associated with adenoma risk among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln or the codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.026). These interactions were not modified by antioxidant intake. However, low antioxidant intake was associated with an inverse association only among subjects with the XRCC1 codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.022), which was independent of unsaturated fat intake. Our data suggest that the XRCC1 codon 194 and codon 399 single nucleotide polymorphisms may modify the effect of unsaturated fatty acid and antioxidant intake and that this XRCC1 effect modification may explain, in part, previously reported inconsistencies on the role of unsaturated fatty acids and adenoma risk.     

Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population

Esophageal squamous cell carcinoma (ESCC), which is prevalent in China, is believed to be induced by environmental carcinogens. Accumulating evidence has shown that individual variation in DNA repair capacity resulting from genetic polymorphism influences risk of environmental carcinogenesis. We therefore investigated the associations between genetic polymorphisms in the DNA repair genes XRCC1 (Arg194Trp and Arg399Gln) and XPD (Asp312Asn and Lys751Gln) and risk of ESCC in an at-risk Chinese population. Genotypes were determined by a PCR-based approach in 433 patients with ESCC and 524 frequency-matched normal controls. We found that individuals with Trp/Trp genotype at XRCC1 Arg194Trp site had a 2-fold increased risk of this disease compared to Arg/Arg genotype (adjusted OR = 1.98; 95% CI 1.26-3.12). Furthermore, when compared to Arg/Arg and Arg/Trp genotype combined, homozygote for Trp/Trp genotype significantly increased the risk of developing ESCC, with the adjusted OR being 2.07 (95% CI 1.34-3.20). However, the XRCC1 Arg399Gln polymorphism was not significantly associated with risk of ESCC, with the adjusted OR being 0.87 (95% CI 0.55-1.37). Neither Asp312Asn nor Lys751Gln polymorphisms in the XPD gene influenced risk of ESCC in our study. These findings suggest that DNA repair gene XRCC1 but not XPD might play a role in esophageal carcinogenesis and might represent a genetic determinant in the development of the cancer.     

XRCC1和XRCC3单核苷酸多态性与晚期非小细胞肺癌铂类药物化疗疗效的相关性

背景与目的 DNA修复基因多态性预测铂类药物化疗敏感性对非小细胞肺癌(non-small cell lung cancer,NSCLC)个体化治疗具有重要意义.本研究旨在探讨X线修复交错互补基因1(X-ray repair cross complementing gene 1,XRCC1)和X线修复交错互补基因3(X-ray repair cross complementing gene 3,XRCC3)单核苷酸多态性与晚期NSCLC患者对铂类药物化疗疗效的关系.方法 采用PCR-RFLP方法检测130例以含铂方案化疗的晚期NSCLC患者外周血DNA中XRCC1 Arg194 Trp、Arg399 Gln和XRCC3 Thr241 Met基因多态性,分析其基因型与化疗疗效的关系.结果 130例晚期NSCLC患者采用含铂方案化疗2个周期后,化疗总有效率为33.8％.XRCC1 194和399基因多态性与铂类药物化疗敏感性相关,而XRCC3 241基因多态性与化疗敏感性无关(P=0.145).携带至少1个XRCC1 194 Trp等位基因者化疗有效率至少是携带Arg/Arg基因型患者的2.5倍(42.1％vs22.2％,OR=2.545,95％CI:1.159-5.590,P=0.020).携带XRCC1399 Arg/Arg基因型者的化疗有效率为45.5％,明显高于携带至少1个Gln等位基因者(21.9％)(OR=0.336,95％CI:0.156-0.722,P=0.005).XRCC1 194和399基因多态性之间存在联合作用,同时携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率明显高于同时携带194 Arg/Arg和399 Arg/Gln基因型者(44.4％ vs 18.8％,OR=3.467,95％CI:1.223-9.782,P=0.019).XRCC1和XRCC3基因多态性在化疗敏感性方面存在一定的联合作用,携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg野生型基因同时又携带XRCC3 241 Thr/Met基因型者的化疗有效率明显高于其它基因型携带者.结论 XRCC1和XRCC3的多态联合可能与晚期NSCLC患者对铂类药物化疗疗效具有相关性.     

Prognostic Significance of GSTP1, XRCC1 and XRCC3 Polymorphisms in Non-small Cell Lung Cancer Patients

Aim: Individual differences in chemosensitivity and clinical outcome in non-small cell lung cancer (NSCLC)patients treatment with platinum-based chemotherapy may be due to genetic factors. Our study aimed toinvestigate the prognostic role of GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy.Methods: A total of 460 cases were consecutively selected from The Affiliated Hospital of Nantong Universitybetween Jan. 2003 to Nov. 2006, and all were followed-up until Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met was conducted by duplex polymerase-chain-reactionwith confronting-two-pair primer methods. Results: Patients with GSTP Val/Val exhibited a shorter survivaltime, and had a 1.89 fold greater risk of death than did those with the IIe/IIe genotype. For XRCC1 Arg194Trp,the variant genotype Trp/Trp was significantly associated with a decreased risk of death from NSCLC whencompared with the Arg/Arg. Individuals carrying XRCC1 399Gln/Gln genotype had a longer survival time,with a lowered risk of death from NSCLC. Conclusion: This study indicated that GSTP1 Ile105Val, XRCC1Arg194Trp and XRCC1Arg399Gln genes have a role in modifying the effect of platinum-based chemotherapyfor NSCLC patients in a Chinese population. Our findings provide information for therapeutic decisions forindividualized therapy in NSCLC cases.     

Implication of Polymorphisms in DNA Repair Genes in Prognosis of Hepatocellular Carcinoma

XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, includinghepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the roleof selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, andgenotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performedby duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicatedXRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time comparedwith patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had asignificantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox’s regressionanalysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC thanArg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers withan HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significancein the prognosis of HCC.     

No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women's Health Study

BACKGROUND: Genetic variation in DNA repair may contribute to differences in the susceptibility of several cancers. We evaluated two polymorphisms in the base excision repair pathway (BER) (XRCC1; Arg194Trp and Arg399Gln) and one polymorphism in the double strand DNA repair pathway (XRCC3; Thr241Met) for their association with breast cancer risk. METHODS: The association was analyzed in a nested case control study of 460 breast cancer cases and 324 cancer-free controls within the Iowa Women's Health Cohort. DNA was obtained from blood samples or paraffin embedded tissues (PET) and all samples were genotyped by one of three genotyping platforms-PCR-RFLP, PCR-INVADER, or Sequenom. RESULTS: None of the three polymorphisms studied were significantly associated with breast cancer risk (XRCC1: Arg194Trp (OR=1.21, 95% CI: 0.78-1.88); Arg399Gln (OR=1.20, 95% CI: 0.80-1.79); XRCC3: Thr241Met (OR=1.04, 95% CI: 0.76-1.41). CONCLUSIONS: These results suggest that independently these polymorphisms of XRCC1 and XRCC3 genes do not contribute significantly to the genetic susceptibility of breast cancer.     

Association of XPD and XRCC1 Genetic Polymorphisms with Hepatocellular Carcinoma Risk

Aim: XRCC1 and XPD are two major repair genes involved in nucleotide excision repair (NER), whichis reported to be associated with risk of several cancers. We explored the association of XRCC1 and XPDpolymorphisms with the risk of HCC. Methods: A total of 410 cases with HCC and 410 health controls werecollected. XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn genotyping wasperformed by duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method.Results: XRCC1 194Trp/Trp was strongly significantly associated with an increased risk of HCC cancer whencompared with the wide-type genotype (OR=2.26, 95% CI=(1.23-5.38). Individuals carrying the XRCC1 399Gln/Gln showed increased risk of HCC (OR=1.74, 95%CI=1.06-2.74). The XPD 751Gln/Gln and Gln allele genotypewere associated with strong elevated susceptibility to HCC (OR=3.51 and 1.42, respectively). Conclusion: Theseresults suggest that polymorphisms in XRCC1 and XPD may have functional significance in risk of HCC.     

Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity

Although several variants of DNA repair genes have been identified, their functional significance has not been determined. Using samples collected from 135 cancer-free women, this study evaluated whether amino acid substitution variants of DNA repair genes contribute to ionizing radiation (IR) susceptibility as measured by prolonged cell cycle G2 delay. PCR-restriction fragment length polymorphism (RFLP) assays were used to determine four genotypes: X-ray repair cross complementing group 1 (XRCC1, exon 6, C/T, 194 Arg/Trp and exon 10, G/A, 399 Arg/Gln), XRCC group 3 (XRCC3, exon 7, C/T, 241 Thr/Met) and apurinic/apyrimidinic endonuclease 1 (APE1, exon 5, T/G, 148 Asp/Glu). Fluorescence-activated cell sorter (FACS) analysis was used to measure cell cycle delay. APE1 (exon 5) genotype was significantly associated with mitotic delay (P = 0.01), with the Glu/Glu genotype having prolonged delay compared with the other two genotypes. The mitotic delay index (mean +/- SD) in women with the APE1 codon 148 Asp/Asp, Asp/Glu and Glu/Glu genotypes was 30.95 +/- 10.15 (n = 49), 30.65 +/- 10.4 (n = 60) and 39.56 +/- 13.12 (n = 21), respectively. There was a significant interaction between family history (FH) and APE1 (exon 5) genotype (P = 0.007) as well as FH and XRCC1 (exon 10) genotype (P = 0.005) in mitotic delay. Lastly, prolonged cell cycle delay was significantly associated with number of variant alleles when APE1 Asp148Glu and XRCC1 Arg399Gln genotypes were evaluated in a four-level model (chi(2) for linear trend = 10.9; P = 0.001). These results suggest that amino acid substitution variants of XRCC1 and APE1 may contribute to IR hypersensitivity.     

Predictive value of XRCC1 and XRCC3 gene polymorphisms for risk of ovarian cancer death after chemotherapy

Objective: To investigate any association between XRCC1 and XRCC3 polymorphisms and outcome ofplatinum-based chemotherapy in ovarian cancer patients. Methods: With a prospective study design was caseswere consecutively collected from January 2005 to January 2007. All 310 included patients were followed-upuntil the end of January 2010. Genotyping of XRCC1 and XRCC3 polymorphisms was conducted by TaqManGene Expression assays. Results: A total of 191 patients died during follow-up. Our study showed a lowersurvival rate in XRCC1 399 Arg/Arg genotype than Gln/ Gln, with a significant increased risk of death (HR=1.69,95%CI=1.07-2.78). Similarly, those carrying XRCC3 Thr/ Thr genotype had a increased risk as compare tothe Met/Met genotype, with a HR (95% CI) of 1.90 (1.12-3.41). There was no significant association betweenXRCC1 Arg194Trp and XRCC1Arg280His gene polymorphisms and ovarian cancer death. Conclusion: Ourstudy demonstrates that polymorphisms in DNA repair genes have roles in the susceptibility and survival ofovarian cancer patients.     

Polymorphisms in GSTM1 and XPD genes predict clinical outcome in advanced oral cancer patients treated with postoperative radiotherapy

Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Ser326Cys, rs1052133), XRCC1 (Arg194Trp, rs1799782, and Arg399Gln, rs25487), XPD (Asp312Asn, rs1799793, and Lys751Gln, rs13181) can predict clinical outcome in 187 oral squamous cell carcinoma patients treated with postoperative radiotherapy. The Cox proportional hazards model was used to evaluate the role of polymorphic genotypes on relapse-free (RFS) and disease-specific (DSS) survival. Deletion polymorphism of GSTM1 gene was significantly associated with DSS. The rs1799793 variant allele showed significant protection in both DSS and RFS. Significant increase in RFS but not in DSS was observed with polymorphic rs13181. The combined analysis of GSTM1 and XPD polymorphisms revealed favorable effect on survival. GSTM1 and XPD variant alleles, independently as well as in combination may serve as important predictors of clinical outcome in radiotherapy-treated OSCC patients. ? 2011 Wiley Periodicals, Inc.     

Genetic Risk of DNA Repair Gene Polymorphisms (XRCC1 and XRCC3) for High Risk Human Papillomavirus Negative Cervical Cancer in Northeast Thailand

To identify risk factors other than high risk human papillomavirus infection for the development of cervicalcancer, functional polymorphisms of DNA repair genes, XRCC1 Arg399Gln and Arg194Trp and XRCC3Thr241Met, were studied among Northeastern Thai women. Cases (n=111) were defined as squamous cellcervical cancer and controls (n=118) were recruited from healthy women without cervical abnormalities. TheXRCC1 194Trp/Trp genotype significantly increased the risk for cervical cancer (OR=5.52; 95%CI=1.14-26.64;p=0.03). Among the HPV infection negative group, significantly higher risks for cervical cancer were visualizedfor XRCC1 399Arg/Gln (adjusted OR=3.69; 95%CI=1.04-13.06; p=0.04) and XRCC1 194Arg/Trp (adjustedOR=4.13; 95%CI=1.13-15.12; p=0.03). This study indicates that variant types of DNA repair genes play partialroles in modifying individual susceptibility to cervical cancer. Since cervical cancer is a multi-factorial disease,the contribution of DNA repair enzymes to the development of cervical cancer, if it exists may be concealed byHPV infection.     

DNA repair gene variants in endometrial carcinoma

Several polymorphisms in the DNA repair gene are thought to have significant effects on cancer risk. In this study, we investigated the association of the polymorphisms in the DNA repair genes, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys, with endometrium cancer risk. Two hundred and sixty-two women were included in the study. Endometrial biopsy was performed, and on the basis of diagnosis and histological examination, women were divided into two groups: a control group (n?=?158) and an endometrial cancer group (n?=?104). Genotypes were determined by PCR-RFLP assays in endometrial carcinoma patients and age-matched controls. In this study, we found that the frequencies of Glu+ and Asp/Glu genotypes in APE, Gln/Gln genotype of XRCC1, Met/Met genotype of XRCC3, Cys+ and Ser/Cys genotypes of HOGG1, His+ and Asp/His genotypes of XPG, and Gln+ and Gln/Gln genotypes of XPD are more prevalent in patients than controls. Frequencies of Thr/Thr genotype in XRCC3 were increased in controls compared with patients and seem to be protected from endometrial cancer. Our findings suggest that XRCC1, XRCC3, XPD, XPG, APE1, and HOGG1 genetic variants may be associated with endometrial cancer in Turkish women.     

Associations between three XRCC1 polymorphisms and glioma risk: a meta-analysis

Glioma, especially its most aggressive histological type glioblastoma, is a challenge to human health due to its poor prognosis. Identifying glioma risk factors will improve early diagnosis to prevent tumor progression. Three polymorphisms of X-ray repair cross-complementing groups 1 (XRCC1) Arg399Gln, Arg194Trp, and Arg280His have drawn attention because of their potential associations with the development of glioma. However, the conclusions from different studies are inconsistent. Here, we performed XRCC1 polymorphism–glioma association analyses on data gathered through searching PubMed, ISI Web of Knowledge, Cochrane, and EBSCO databases and meta-analyzing extracted eligible studies. For XRCC1 Arg399Gln (G>A) polymorphism, there were 12 studies with 4,356 cases and 6,616 controls; for Arg194Trp (C>T) polymorphism, there were nine studies with 3,760 cases and 5,971 controls; and for Arg280His (G?>?A) polymorphism, there were five studies with 1,883 cases and 3,144 controls. Odds ratios as well as their 95 % confidence intervals in three genetic models were used to estimate the strength of the association between XRCC1 genotypes and glioma risk. Based on our main analyses, increased risk was observed in Arg399Gln codominant and dominant models and Arg194Trp homozygous codominant and recessive models. In the stratified analyses for some genetic models, Arg399Gln and Arg194Trp were recognized as risk factors in the Asian but not in the Caucasian population. No associations were detected for Arg280His in any genetic model. This meta-analysis indicates that XRCC1 399Gln and 194Trp variants increase glioma risk. Both of these polymorphisms might raise the susceptibility of glioma in Asian populations.     

Associations Between XRCC1 Arg399Gln,Arg194Trp,and Arg280His Polymorphisms and Risk of Differentiated Thyroid Carcinoma: A Meta-analysis

Background: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 geneand risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory.Methods: We performed a meta-analysis in the present study using STATA 11.0 software to clarify any associations.Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 publishedstudies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. Results: No significantassociations were observed between Arg399Gln and DTC risk in all genetic models within the overall andsubgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphismwas associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed toDTC susceptibility in Caucasians. Conclusions: Our meta-analysis suggests that XRCC1 Arg194Trp may be arisk factor for DTC development.     

MS-920: DNA repair gene polymorphisms, diet and colorectal cancer risk in Taiwan

This hospital-based case-control study examined whether polymorphic DNA repair genes: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, play a role in the susceptibility to colorectal cancer. We genotyped these polymorphisms for 727 newly diagnosed colorectal adenocarcinoma cases and 736 age and sex matched healthy controls in Taiwan. Although the colorectal cancer risk was not significantly associated with these genes, the risk was significantly elevated in younger subjects (< or =60 years) with the XRCC1 399Arg/Arg genotype compared to those with XRCC1 399Gln allele (OR=1.46, 95% CI=1.06-2.99, P=0.02). The stratified analysis showed that XRCC3 interacted with meat consumption (P for interaction=0.02), but was limited to the low meat consumption (OR=2.34, 95% CI=1.28-4.29). Our results suggest that the XRCC1 Arg399Gln polymorphism may contribute to the risk of early-onset colorectal cancer and the XRCC3 Thr241Met polymorphism may modify the risk for meat-associated colorectal cancer.     

Polymorphisms in the DNA repair gene XRCC1 associated with basal cell carcinoma and squamous cell carcinoma of the skin in a Korean population

DNA in most cells is regularly damaged by endogenous and exogenous mutagens. Unrepaired damage can result in apoptosis or may lead to unregulated cell growth and cancer. Inheritance of genetic variants at one or more loci results in reduced DNA repair capacity. This hospital-based case-control study examined whether polymorphisms in the DNA repair gene X-ray repair cross-complementing groups 1 ( XRCC1 ) (Arg194Trp[C > T], Arg280His[G > A] and Arg399Gln[G > A]) play a role in susceptibility to skin cancer. We genotyped these polymorphisms for 212 histopathologically confirmed skin cancer cases ( n  = 114 basal cell carcinoma, n  = 98 squamous cell carcinoma) and 207 age- and sex-matched healthy control cases in Korea. We found that individuals with the Arg/Gln and Arg/Gln + Gln/Gln genotypes at XRCC1 Arg399Gln(G > A) had an approximately 2-fold increased risk of basal cell carcinoma compared to individuals with the Arg/Arg genotype (adjusted odds ratio [AOR] = 2.812, 95% confidence interval [CI] 1.32–5.98, and AOR = 2.324, 95% CI 1.11–4.86). However, we observed that the 194Trp allele of the Arg194Trp(C > T) polymorphism was inversely associated with squamous cell carcinoma risk (Trp/Trp, AOR = 0.06, 95% CI 0.006–0.63). Our data suggest that the Arg194Trp and Arg399Gln polymorphisms may be differentially associated with skin cancer risk. ( Cancer Sci 2007; 98: 716–720)     

Polymorphisms of DNA repair gene XRCC1 and risk of glioma: a case-control study in Southern China

Objective: This study aimed to examine associations between polymorphisms in the X-ray cross-complementing group 1 (XRCC 1) gene and risk of glioma in a Chinese population. Methods: We performed a hospital-based case-control study with 271 cases and 289 controls in Guangdong province, China. Cases were patients newly diagnosed with pathologically confirmed glioma in two hospitals between June 2006 and May 2010. Controls were individuals without cancer, frequency matched by sex and age. Three SNPs in XRCC1 gene, Arg399Gln (rs25487), Arg194Trp (rs1799782) and Arg280His (rs25489), were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method. Unconditional logistic regression was used to estimate the odds ratios (ORs) of polymorphisms in XRCC1 gene for glioma. Results: The Arg399Gln polymorphism was significantly associated with risk of glioma. Individuals with the Gln/Gln genotype had a significantly increased likelihood of developing glioma compared with those with the Arg/Arg genotype (adjusted OR = 1.93, 95% CI: 1.04 - 3.58), especially among males and individuals aged 50 years or older. Conclusion: The XRCC1 Arg399Gln polymorphism may be a useful susceptibility biomarker for glioma. Further studies in Chinese populations with larger sample sizes are now warranted.