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.     

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

Background: X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repairpathway, as a scaffold protein that brings together proteins of the DNA repair complex. XRCC1 is reported tobe a candidate influence on cancer risk. The aim of our present study was to assess the association of rs1799782(Arg194Trp) and rs25487 (Arg399Gln) XRCC1 gene polymorphisms with breast cancer in the Saudi population.Materials and Methods: The two SNP’s were analyzed in breast cancer patients and healthy control subjects.Genotypes were determined by TaqMan SNP genotype analysis technique and data were analyzed using Chisquareor t test and logistic regression analysis by SPSS16.0 software. Results and Conclusions: Results showedthat rs1799782 significantly increased susceptibility to breast cancer with Arg/Trp, Arg/Trp+Trp/Trp genotypesand at Trp allele overall study. It also increased risk of breast cancer in older age patients (above 48) and withthe ER positive category. XRCC1rs25487 (Arg399Gln) did not showed any significant association. In conclusionthe XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population.Confirmation of our findings in larger populations of different ethnicities is warranted.     

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women

Background: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study. Materials and Methods: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population. Conclusions: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.     

Polymorphisms in DNA Repair Genes and Risk of Glioma and Meningioma

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modifycancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repairgenes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotypingof XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser,ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate formaton the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls(P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher riskwhen compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associatedwith elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp,XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This findingcould be useful in identifying the susceptibility genes for these cancers.     

Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus

Population-based studies have reported significant associations between specific genetic polymorphisms and breast cancer susceptibility. A number of studies have demonstrated that common variants of genes involved in the DNA repair pathway act as low penetrance breast cancer susceptibility alleles. We aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the DNA repair genes XRCC1, XRCC2 and XRCC3 and breast cancer in MASTOS, a population-based case–control study of 1,109 Cypriot women with breast cancer diagnosed between 40 and 70 years and 1,177 age-matched healthy controls. Five coding SNPs were genotyped including rs1799782, rs25489 and rs25487 in XRCC1, rs3218536 in XRCC2 and rs861539 in XRCC3. Homozygous XRCC1 280His carriers had an increased risk of breast cancer (odds ratio 4.68; 95% CI 1.01–21.7; P = 0.03). The XRCC2 188His allele was associated with a marginal protective effect for breast cancer (odds ratio 0.79; 95% CI 0.62–1.00; P = 0.05). No significant associations were observed between the other three SNPs and breast cancer. This study suggests that genetic variation in SNPs in XRCC1 and XRCC2 genes may influence breast cancer susceptibility.     

Association between the DNA Repair Gene XRCC3 rs861539 Polymorphism and Risk of Osteosarcoma: a Systematic Review and Meta-Analysis

Objective: Although there are a few studies investigating the relation between X-Ray Repair Cross Complementing 3 (XRCC3) gene rs861539 polymorphism and osteosarcoma (OSA), the results are inconsistent. Therefore, we performed this systematic review and meta-analysis to clarify the associations between XRCC3 rs861539 polymorphism and OSA risk. Methods: We have retrieved published literature from PubMed, Google scholar, and ISI Web of Knowledge up to 25 January 2017. Odds ratios were pooled using either fixed-effects or random effects models. Overall and subgroup analyses were performed. Statistical analysis was performed running comprehensive meta-analysis (CMA) 2.0 software. Results: A total of four studies with 515 cases and 1,109 controls were identified in order to investigate the association between XRCC3 rs861539 polymorphism and OSA risk. The results showed that XRCC3 rs861539 polymorphism was associated with OSA in allelic (T vs. C: OR= 1.563, 95% CI: 1.244-1.963, p= <0.001), homozygote (TT vs. CC: OR= 2.574, 95% CI: 1.573-4.212, p= <0.001), dominant (TT+TC vs. CC: OR= 1.255, 95% CI: 1.011-1.558, p= 0.039), and recessive (TT vs. TC+CC: OR= 2.224, 95% CI: 1.393-3.552, p= 0.001), but not with heterozygote (TC vs. CC: OR= 1.361, 95% CI: 0.982-1.885, p= 0.064). The XRCC3 rs861539 polymorphism conferred susceptibility to OSA in Asians, but not in Caucasians. Additionally, we observed no evidence of publication bias. Conclusion: To the best of our knowledge, this is the first meta-analysis investigating the association between XRCC3 rs861539 polymorphism and OSA risk. Our results revealed a significant association between the XRCC3 rs861539 polymorphism and risk of OSA, especially in Asian populations. Future more comprehensive and well-designed case control studies with larger sample size are needed to warrant these findings.     

DNA Repair Genes Polymorphisms: Impact on Acute Myeloid Leukemia Patients Outcome

Background: ATM; XRCC6 and LIG4 genes play an important role in repairing the double-strand DNA breaks and maintaining the genome stability. Single nucleotide polymorphisms (SNPs) in these genes could affect these genes expression and function. The aim of this study was to address the effect of SNP of the DNA repairing genes on corresponding  gene expression as well as AML patient’s outcome. Subjects and Methods: This is cross sectional study included 95 newly diagnosed AML patients. For all subjects included in our study SNPs  and expression of ATM (rs189037G>A), XRCC6 (rs2267437C>G) and LIG4 (rs1805388C>T) genes were evaluated by RFLP and real time PCR. Results:The following SNPs in ATM (AA); XRCC6 (GG); and LIG4 (TT) are associated with down regulation of the corresponding genes (P<0.001). The lower expression of ATM and LIG4 genes are associated with shorter OS and DFS. Cox regression multivariate analysis revealed that lower expression of ATM HR : 2.02 (CI: 1.12-3.64; p=0.020. Conclusion: The following SNPs of ATM (AA); XRCC6 (GG); and LIG4 (TT) are associated with down regulation of corresponding genes expression. ATM and XRCC6 lower expression are predictors of OS while ATM is predictor of DFS and could be used for optimizing the AML therapy.     

DNA修复基因多态性影响晚期胃癌卡培他滨联合奥沙利铂化疗的临床预后

目的:探讨DNA修复基因(ERCC1、ERCC2、XRCC1)单核苷酸多态性对胃癌患者卡培他滨联合奥沙利铂化疗敏感性的相关性.方法:本回顾性研究选取XELOX作为一线化疗方案的100例晚期胃癌患者为研究对象,检测分析三个基因六个单核苷酸多态性位点(ERCC1 rs11615;ERCC2 rs13181,rs1799793;XRCC1 rs25487,rs25489,rs1799782),同时分析其与临床预后的关系.结果:XRCC1 rs25487的A/G等位基因频率、AG/AA/GG基因分布频率均与疾病化疗敏感性和无进展生存期有关,携带GG基因型患者疗效好(P<0.05),中位PFS为8.00个月(95%CI:6.34~9.66);ERCC2 rs13181的G/T等位基因频率、GG/GT/TT基因分布频率与疾病化疗敏感性和无进展生存期明显相关,携带TT基因型患者疗效好(P<0.05),中位PFS为7.46个月(95%CI:6.45~8.48).COX比例风险模型显示ERCC2 rs13181 G/T基因型是晚期胃癌无进展生存期的独立风险因素之一(HR=0.72,95%CI:0.53~0.97,P=0.025).结论:ERCC2 rs13181基因多态性可能是评估接受XELOX化疗晚期胃癌患者预后的关键指标.     

Association Between XRCC5, 6 and 7 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

Objective: Non-homologous end joining (NHEJ) is a pathway for repairing DNA double-strand breaks.Recent publications indicated that XRCC5, XRCC6 and XRCC7 genes may participate in the pathogenesis ofbreast cancer. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigateassociations between XRCC5, XRCC6 and XRCC7 genetic polymorphisms in the NHEJ pathway and breastcancer risk. Methods: Studies focusing on the relationship between genetic polymorphisms in XRCC5, XRCC6and XRCC7 genes and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase,Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers.The meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Theodds ratio (OR) with 95% confidence interval (95%CI) was calculated based on the extracted data. Results:According to the inclusion criteria, we final included seven studies with a total of 2,864 breast cancer cases and3,060 healthy controls. Meta-analysis results showed that rs3835 (G>A) and rs828907 (G>T) in XRCC5 gene,and rs132793 (G>A) in XRCC6 gene might increase the risk of breast cancer, while rs132788 G>T and rs6002421(A>G) might be protective factors. However, there was no relationship between XRCC7 genetic polymorphismsand the risk of breast cancer. Conclusion: This meta-analysis suggests that the rs3835 G>A and rs828907 G>Tin XRCC5 gene, rs6002421 (A>G), rs132788 (G>T) and rs132793 (G>A) in XRCC6 gene might be risk factorsfor breast cancer, while the rs132788 (G>T) and rs6002421 (A>G) in XRCC6 gene might be protective.     

Association between DNA repair gene polymorphisms and risk of glioma: A systematic review and meta-analysis

Background

Association studies of germline DNA repair single nucleotide polymorphisms (SNPs) and glioma risk have yielded inconclusive results. We therefore performed a systematic review and meta-analysis of studies investigating this association.

Methods

We identified 27 eligible studies investigating 105 SNPs in 42 DNA repair genes. Of these, 10 SNPs in 7 genes were analyzed in at least 4 studies and were therefore included in our meta-analysis. The meta-analysis was performed for homozygote comparison, heterozygote comparison, and dominant and recessive models by applying a fixed- or random-effects model. The funnel and forest plots were created using RevMan software.

Results

We found that SNPs rs3212986 (odds ratio [OR] = 1.35 (1.08–1.68), P = .008), rs13181 (OR = 1.18 (1.06–1.31), P = .002), and rs25487 (OR = 1.12 (1.03–1.22), P = .007) in DNA repair genes ERCC1, ERCC2 (XPD), and XRCC1 may increase the risk of glioma, while polymorphisms rs1136410 (OR = 0.78 (0.68–0.89), P = .0004) and rs12917 (OR = 0.84 (0.73–0.96), P = .01) in PARP1(ADPRT) and MGMT are associated with decreased susceptibility to glioma. No evidence of significant associations between ERCC2 rs1799793, OGG1 rs1052133, XRCC1 rs25489, XRCC1 rs1799782, or XRCC3 rs861539 and risk of glioma was observed.

Conclusion

This study provides evidence that DNA repair genes ERCC1, ERCC2, and XRCC1 might be low-penetrance glioma-risk genes, while MGMT and PARP1 polymorphisms may confer protection against glioma.     

XRCC1和XRCC2的基因多态性在乳腺癌治疗中的临床意义

目的:乳腺癌是女性常见的恶性肿瘤之一,其发生发展与遗传因素十分密切,寻找与乳腺癌发生、病理、治疗及预后相关的分子标志物对于该病的治疗具有重要的指导意义。XRCC是参与DNA损伤修复的重要基因。XRCC1及XRCC2基因的多态性已被研究与多种肿瘤易感性及生物学行为有关。本实验研究XRCC1 和XRCC2 多态性与中国女性乳腺癌发病风险、临床病理（腋窝淋巴结转移状态）及预后(复发和转移)的相关性,以探讨其在乳腺癌临床治疗中的潜在价值。方法:采用PCR-RFLP方法检测60例原发性乳腺癌患者新鲜血标本中XRCC1 Arg399Gln、XRCC2 C41657T、XRCC2 G4234C多态,采用SAS 9.1.3统计软件分析基因型与乳腺癌发病风险、临床病理及预后的相关性。结果:XRCC1 Arg399Gln 不同基因型与乳腺癌的发病风险不存在统计学相关性(P>0.05); XRCC1 Arg399Gln与乳腺癌的腋窝淋巴结转移情况及乳腺癌的远处转移、局部复发不存在相关性(P>0.05);XRCC2 C41657T、XRCC2 G4234C 基因型与乳腺癌的发病风险均无显著相关(P>0.05);XRCC2 C41657T C/T和T/T基因型的多态性可能与乳腺癌的腋窝淋巴结转移状态、乳腺癌的远处转移及局部复发具有相关性(P<0.05)。结论:XRCC1 Arg399Gln G/G、XRCC2 C41657T、XRCC2 G4234C 基因型可能均与乳腺癌的发病风险无关。XRCC2 C41657T C/T和T/T基因型的多态性可能与乳腺癌的腋窝淋巴结转移状态、乳腺癌的远处转移及局部复发具有相关性。     

DNA Repair Gene Polymorphisms at XRCC1, XRCC3, XPD,and OGG1 Loci in the Hyderabad Population of India

Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to thepresence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity. Materials and Methods: In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and otherpopulations. Results and Conclusions: The genotype and allele frequency distribution at the four DNA repairgene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these genepolymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccanregion of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms inthe Deccan Indian population.     

Genetic Variations of RAD51 and XRCC2 Genes Increase the Risk of Colorectal Cancer in Bangladeshi Population

Objectives: In case of Bangladeshi population, no report is observed till now showing the genetic variations of RAD51 (rs1801320) and XRCC2 (rs3218536) genes polymorphism having association with colorectal cancer risk. For this reason the aim of this study is to ascertain their interrelation with colorectal cancer occurrence in Bangladeshi population. Materials and Methods: A case control study was conducted where 200 colorectal cancer patients and 200 healthy volunteers were figured for this research using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Here, in case of RAD51 (rs1801320), G/C heterozygous genotype was found significant (p=0.037; OR=1.64; 95% CI=1.03 to 2.6). On the other hand, G/G genotype was not found statistically significant (p=0.423; OR=1.61; 95% CI=0.49 to 5.22) and significance was observed for GC+GG (p=0.030; OR=1.63; 95% CI=1.05 to 2.55). In case of XRCC2 (rs3218536), C/T heterozygous genotype was remarked statistically significant (p=0.033; OR=1.60; 95% CI=1.04 to 2.46). The T/T genotype was not recorded statistically significant (p=0.237; OR=1.65; 95% CI=0.72 to 3.76) but significance found for CT+TT (p=0.027; OR=1.61; 95% CI=1.05 to 2.45). Moreover, it is found that the risk factor of developing CRC is observed in G/C, C/T heterozygote and GC+GG, CT+TT (heterozygote+ mutant) in RAD51 (rs1801320) and XRCC2 (rs3218536) respectively although no significance is observed in case of G/G and T/T mutant. Conclusions: So, the association of RAD51 (rs1801320) and XRCC2 (rs3218536) genes polymorphism with colorectal cancer risk is observed in Bangladeshi population.     

TNRC9和FGFR2基因多态性与湖北地区汉族人群乳腺癌患病风险研究

目的:研究探讨TNRC9基因rs3803662和FGFR2基因rs17102287单核苷酸多态性(SNP)及两SNP连锁与湖北地区汉族妇女乳腺癌易感性的关系.方法:抽取汉族510例乳腺癌患者和550例健康妇女外周血,分离淋巴细胞,抽提基因组DNA,检测TNRC9 rs3803662和FGFR2 rs17102287 的基因多态性,计算基因型和等位基因频率,研究各基因型以及基因SNP连锁之间对乳腺癌风险的影响.结果:TNRC9基因SNP位点rs3803662的C/C、C/T和T/T基因型频率在病例组和对照组分别为13.0％、46.4％、40.6％和7.3％、52.1％、40.6％,其基因型频率相比差异有统计学意义,x2=9.40,P=0.043.而等位基因频率两组相比差异均无统计学意义;FGFR2基因SNP位点rs17102287的C/C、C/T和T/T基因型频率在病例组和对照组中差异无统计学意义;等位基因频率两组相比差异无统计学意义.两基因连锁分析D'=0.087,r2=0.085,没有明显连锁不平衡现.结论:TNRC9基因rs3803662多态性与汉族妇女乳腺癌易感性有关,FGFR2基因rs17102287多态性及其与TNRC9基因rs3803662单倍体连锁与湖北地区汉族人群妇女乳腺癌易感性无相关性.     

Genetic variability in DNA repair and cell cycle control pathway genes and risk of smoking-related lung cancer

DNA repair and cell cycle control play an important role in the repair of DNA damage caused by cigarette smoking. Given this role, functionally relevant single nucleotide polymorphisms (SNPs) in genes in these pathways may well affect the risk of smoking-related lung cancer. We examined the relationship between 240 SNPs in DNA repair and cell cycle control pathway genes and lung cancer risk in a case-control study of white current and ex-cigarette smokers (722 cases and 929 controls). Additive, dominant, and recessive genetic models were evaluated for each SNP. A genetic risk summary score was also constructed. Odds ratios (OR) for lung cancer risk and 95% confidence intervals (95% CI) were estimated using logistic regression models. Thirty-eight SNPs were associated with lung cancer risk in our study population at P?相似文献   

Haplotype-based case–control study of DNA repair gene XRCC3 and hepatocellular carcinoma risk in a Chinese population

Previous studies indicated that the human X-ray repair complementing group 3 gene (XRCC3) plays an important role in hepatocellular carcinoma (HCC) susceptibility. We aimed to investigate the association of XRCC3 genetic polymorphism with HCC risk. This study was conducted in a Chinese Han population consisting of 300 HCC cases and 300 sex- and age-matched cancer-free controls. Three genetic variants (rs861539, rs12432907, and rs861537) were genotyped by the TaqMan® SNP Genotyping Assay. Our findings suggested that the TT genotype and T allele from rs861539 genetic variants were statistically associated with HCC risk. The TT genotype was statistically associated with the increased risk of HCC compared to CC wild genotype (P?<?0.001). And the T allele was more common in the HCC patients than that in the control subjects. (OR?=?1.97, 95 % confidence interval (CI) 1.457?~?2.659, P?<?0.001). Haplotype-based case–control study analysis indicated that TTG haplotype was more frequent in HCC groups than in the control group (odds ratio (OR)?=?1.967, 95 % CI 1.456?~?2.658); however, the CTG haplotype is more common in the control group than that in the HCC group (OR?=?0.550, 95 % CI 0.430?~?0.703; P?<?0.001). Our data indicated that genetic variants of the XRCC3 gene were statistically associated with HCC risk in a Chinese population.     

Genetic Association of XRCC1 Gene rs1799782, rs25487 and rs25489 Polymorphisms with Risk of Thyroid Cancer: a Systematic Review and Meta-Analysis

Background: A number of case-control studies have evaluated associations between the X-ray cross complementary group 1 protein (XRCC1) gene rs1799782 (Arg194Trp), rs25487 (Arg399Gln) and rs25489 (Arg280His) polymorphisms and thyroid cancer (TC) risk, but the results remain inconclusive. Materials and Methods: A systematic literature search was performed using PubMed and Google Scholar Search. According to defined criteria data were extracted and pooled odds ratios with 95% confidence intervals were calculated under five genetic models. Results: A total of 8 studies with 1,672 cases and 2,805 controls for the rs1799782 polymorphism, 14 studies with 2,506 cases and 5,180 controls for the rs25487 polymorphism, and 11 studies with 2,197 cases and 4,761 controls for the rs25489 polymorphism were included in this meta-analysis. Overall, there was a statistical association between XRCC1 rs1799782 polymorphism and TC risk with the homozygote genetic model (TT vs. CC: OR = 1.815, 95% CI = 1.115-2.953, p= 0.016) and the recessive genetic model (TT vs. TC+CC: OR = 1.854, 95% CI = 1.433-2.399, p= <0.001). In the subgroup analysis by ethnicity, significantly increased TC risk was observed only in Asians under the recessive model (TT vs. TC+CC: OR = 1.816, 95% CI = 1.398-2.358, p= <0.001). In addition, there was no positive association between XRCC1 rs25487 and rs25489 polymorphisms and risk of TC. However, there was a significant association between XRCC1 rs25487 polymorphism risk of TC among Caucasians with allele genetic comparison (A vs. G: OR= 0.882, 95% CI = 0.794-0.979, p= 0.136) and dominant genetic comparison (AA+AG vs. GG: OR=0.838, 95% CI = 0.728-0.965, p= 0.014). Conclusions: The results of our meta-analysis suggest an increased risk of TC with the XRCC1 rs1799782 and rs25487 polymorphisms. However, the XRCC1 rs25489 polymorphism appeared to be without influence.     

DNA修复基因XPD XPC XRCC4基因多态性与结直肠癌易感性的关联性研究

  目的  探讨DNA修复基因XPD rs13181（codon751A/C,Lys751Gln）、rs238406（codon156C/A,Arg156Arg）、XPC rs2279017（i11C/A）和XRCC4 rs3734091（codon247T/C,Ala247Ser）的单核苷酸多态性与结直肠癌易感性的关系。  方法  采用TaqMan技术对2013年4月至2016年1月北京肿瘤医院收治的338例结直肠癌患者（病例组）和315例健康者（对照组）进行多态位点基因型的检测。  结果  XPD rs13181基因型GT和等位基因G增加个体结直肠癌的发病风险（GT>TT,adjusted OR=1.69,95%CI:1.15~2.47,P=0.007;G>T,adjusted OR=1.77,95%CI:1.19~2.64,P=0.005）;XRCC4 rs3734091基因型GT和等位基因T增加个体结直肠癌的易感性（GT>GG,adjusted OR=9.02,95%CI:5.61~14.50,P＜0.001;T>G,adjusted OR=4.06,95%CI:2.49~6.61,P＜0.001）;XPD rs13181和rs238406的单倍体型GT显著降低结直肠癌的发病风险（adjusted OR=0.39,95%CI:0.18~0.85,P=0.018）。XPCrs2279017等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=28.43,95%CI:6.85~117.95,P＜0.001）以及XPD rs13181等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=10.24,95%CI:4.69~22.35,P＜0.001）显著增加个体结直肠癌的易感性。  结论  XPD rs13181和XRCC4 rs3734091位点的多态性与结直肠癌的易感性相关。      

Association of Single Nucleotide Polymorphisms (SNPs) in Genes Encoding for Folate Metabolising Enzymes with Glioma and Meningioma in Indian Population

Background: The association of primary brain tumors with Single Nucleotide polymorphisms (SNPs) in genes offolate metabolising enzymes have been reported to vary among different ethnic population. Here, we have studied theassociation of SNPs of folate metabolizing genes with the primary brain tumors (glioma and meningioma) in North Indianpopulation. Methods: SNPs of genes coding for folate metabolizing enzymes was carried out in 288 study populationfrom North India [Glioma (n=108), Meningioma (n=76) and healthy-control (n=104)]. The allele-specific polymerasechain reaction (ARMS-PCR) was used to analyse the SNP A1298C of the MTHFR (Methylenetetrahydrofolate-reductase)and the SNP A66G of the methionine synthase reductase (MTRR) genes. The PCR-RLFP (Restriction Fragment LengthPolymorphism) was used to analyse the SNP C677T of the Methylene tetrahydrofolate-reductase and the SNP A2756Gof the methionine-synthase (MTR) genes. Serum homocysteine, vitamin B12 and folate levels were evaluated in controls/patients serum using Chemiluminescence immunoassay and the levels were correlated with SNPs genotype. Results:The CC genotype of MTHFR A1298C was observed to have reduced risk of having meningioma than AA genotype(odd ratio=0.62, 95%CI 0.32-0.97, p=0.03). Similarly, the AG genotype of MTRR A66G showed reduced risk ofglioma than AA genotype (odd ratio=0.56, 95%CI 0.32-0.97, p=0.039). Furthermore, in patients with AA genotype ofMTR A2756G and CT genotype of MTHFR C677T showed higher serum homocysteine level than GG genotype (8.6μmol/L, p=0.048) and CC genotype (11.2μmol/L, p=0.039) respectively. Conclusion: Our findings provide an insightinto the risk association of SNPs in MTHFR A1298C and MTRR A66G genes with glioma/meningioma patients.Further studies are needed to evaluate their clinical implications.     

Impact of Polymorphism in Base Excision Repair and Nucleotide Excision Repair Genes and Risk of Cervical Cancer: A Case-Control Study

Background: Last few years, several studies all over the world revealed the association of DNA repair genes with risk of developing different type of cancers, but were ambiguous to support the evidences in case of cervical cancer risk. These differences in earlier studies directed us to study the association of polymorphisms of BER genes (XRCC1, hOGG1, XPC) and NER genes (XPC, XPD) with cervical cancer susceptibility in the women of rural population of Maharashtra. Materials and Methods: The genetic polymorphism in BER and NER pathway genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using DNA isolated from intravenous blood samples of patients and normal controls. The study included 400 clinically confirmed cervical cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The association of polymorphisms was confirmed by Odds ratio (OR) with 95% confidence interval. Results: The single nucleotide polymorphism (SNP) of BER genes including XRCC1, hOGG1 and APE1 were analyzed and the results were noted that 27466AA (OR=4.88; 95% CI: 3.61- 6.60; p<0.0001) and 28152AA (OR=2.89; 95% CI: 1.57- 5.31; p=0.0005) genotypes of XRCC1 (rs25489, rs25487) were significantly associated with cervical cancer risk. The 1245GG genotype of hOGG1 (rs1052133) (OR=45.30; 95% CI: 3.76- 7.46; p=0.001) also showed significant correlation, whereas 2197GG genotype of APE1 (rs1130409) gene showed negative association with cervical carcinogenesis (OR=0.59; 95% CI: 0.35- 0.97; p=0.005). Similarly when we studied SNPs of NER genes including XPC and XPD genes, 21151TT genotype of XPC (rs 2228000) was positively associated with cervical cancer development and 23591AA genotype of XPD (rs1799793) showed negative association (OR=0.34; 95% CI: 0.17- 0.64; p=0.001). Conclusion: The findings from this study supported that rs25489, rs25487SNPs of XRCC1, rs1052133 of hOGG1 and rs2228000 of XPC may increase cervical cancer risk, whereas rs1130409 SNP of APE1 and rs1799793 SNP of XPD gene lower the risk of cervical cancer in the studied population.