• Title, Summary, Keyword: XRCC3

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Genetic Polymorphisms of DNA Repair Genes XRCC1 and XRCC3 and Risk of Colorectal Cancer in Chinese Population

  • Zhao, Yi;Deng, Xin;Wang, Zhen;Wang, Qiang;Liu, Yixia
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.665-669
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    • 2012
  • Aim: The distribution of DNA repair gene XRCC1 and XRCC3 genotypes was used to assess the potential influence of genetic polymorphisms on risk of colorectal cancer, and interactions with other factors. Methods: a 1:2 matched case-control study was conducted with 485 cases and 970 controls. XRCC1 and XRCC2 genotype polymorphisms were based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. Results:The XRCC1 399Cln allele polymorphism was found to be associated with an increased colorectal cancer risk, while an non-significant inversely association was noted for XRCC3 241Thr/Thr genotype. We also found that individuals with the XRCC1 399 Gln and XRCC3 241Met alleles had an elevated risk, while XRCC3241Thr/Thr was proctective. Conclusion: This study is the first to provide evidence of importance of XRCC1 and XRCC3 gene polymorphisms for risk of colorectal cancer in the Chinese population.

Predictive Value of XRCC1 and XRCC3 Gene Polymorphisms for Risk of Ovarian Cancer Death After Chemotherapy

  • Cheng, Chun-Xia;Xue, Min;Li, Kai;Li, Wu-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2541-2545
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    • 2012
  • Objective: To investigate any association between XRCC1 and XRCC3 polymorphisms and outcome of platinum-based chemotherapy in ovarian cancer patients. Methods: With a prospective study design was cases were consecutively collected from January 2005 to January 2007. All 310 included patients were followed-up until the end of January 2010. Genotyping of XRCC1 and XRCC3 polymorphisms was conducted by TaqMan Gene Expression assays. Results: A total of 191 patients died during follow-up. Our study showed a lower survival 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 to the Met/Met genotype, with a HR (95% CI) of 1.90 (1.12-3.41). There was no significant association between XRCC1 Arg194Trp and XRCC1Arg280His gene polymorphisms and ovarian cancer death. Conclusion: Our study demonstrates that polymorphisms in DNA repair genes have roles in the susceptibility and survival of ovarian cancer patients.

Correlation between Selected XRCC2, XRCC3 and RAD51 Gene Polymorphisms and Primary Breast Cancer in Women in Pakistan

  • Qureshi, Z.;Mahjabeen, I.;Baig, R.M.;Kayani, M.A.
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10225-10229
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    • 2015
  • Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.

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

  • Ke, Hong-Gang;Li, Jun;Shen, Yi;You, Qing-Sheng;Yan, Yu;Dong, Han-Xuan;Liu, Jun-Hua;Shen, Zhen-Ya
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4413-4416
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    • 2012
  • 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 to investigate 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 University between Jan. 2003 to Nov. 2006, and all were followed-up until Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met was conducted by duplex polymerase-chain-reaction with confronting-two-pair primer methods. Results: Patients with GSTP Val/Val exhibited a shorter survival time, 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 when compared 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, XRCC1 Arg194Trp and XRCC1Arg399Gln genes have a role in modifying the effect of platinum-based chemotherapy for NSCLC patients in a Chinese population. Our findings provide information for therapeutic decisions for individualized therapy in NSCLC cases.

Polymorphisms in DNA Repair Genes and Risk of Glioma and Meningioma

  • Luo, Ke-Qin;Mu, Shi-Qing;Wu, Zhong-Xue;Shi, Yi-Ni;Peng, Ji-Cai
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.449-452
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    • 2013
  • Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His 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 risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with 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 finding could be useful in identifying the susceptibility genes for these cancers.

Prediction Value of XRCC 1 Gene Polymorphism on the Survival of Ovarian Cancer Treated by Adjuvant Chemotherapy

  • Miao, Jin;Zhang, Xian;Tang, Qiong-Lan;Wang, Xiao-Yu;Kai, Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5007-5010
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    • 2012
  • Objective: We conducted a prospective study to test the association between three amino acid substitution polymorphismic variants of DNA repair genes, XRCC1 (Arg194Trp), XRCC1(Arg280His) and XRCC1 (Arg399Gln), and clinical outcome of ovarian cancer patients undergoing adjuvant chemotherapy. Methods: 195 patients with primary advanced ovarian cancer and treated by adjuvant chemotherapy were included in our study. All were followed-up from Jan. 2007 to Jan. 2012. Genotyping of XRCC1 polymorphisms was conducted by TaqMan Gene Expression assays. Results: The XRCC1 194 Trp/Trp genotype conferred a significant risk of death from ovarian cancer when compared with Arg/Arg (HR=1.56, 95%CI=1.04-3.15). Similarly, those carrying the XRCC1 399 Gln/Gln genotype had a increased risk of death as compared to the XRCC1 399Arg/Arg genotype with an HR (95% CI) of 1.98 (1.09-3.93). Conclusion: This study is the first to provide evidence that XRCC1 gene polymorphisms would well be useful as surrogate markers of clinical outcome in ovarian cancer cases undergoing adjuvant chemotherapy.

Increased Risk of Differentiated Thyroid Carcinoma with Combined Effects of Homologous Recombination Repair Gene Polymorphisms in an Iranian Population

  • Fayaz, Shima;Karimmirza, Maryam;Tanhaei, Shokoofeh;Fathi, Mozhde;Torbati, Peyman Mohammadi;Fard-Esfahani, Pezhman
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6727-6731
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    • 2013
  • Homologous recombination (HR) repair has a crucial role to play in the prevention of chromosomal instability, and it is clear that defects in some HR repair genes are associated with many cancers. To evaluate the potential effect of some HR repair gene polymorphisms with differentiated thyroid carcinoma (DTC), we assessed Rad51 (135G>C), Rad52 (2259C>T), XRCC2 (R188H) and XRCC3 (T241M) polymorphisms in Iranian DTC patients and cancer-free controls. In addition, haplotype analysis and gene combination assessment were carried out. Genotyping of Rad51 (135G>C), Rad52 (2259C>T) and XRCC3 (T241M) polymorphisms was determined by PCR-RFLP and PCR-HRM analysis was carried out to evaluate XRCC2 (R188H). Separately, Rad51, Rad52 and XRCC2 polymorphisms were not shown to be more significant in patients when compared to controls in crude, sex-adjusted and age-adjusted form. However, results indicated a significant difference in XRCC3 genotypes for patients when compared to controls (p value: 0.035). The GCTG haplotype demonstrated a significant difference (p value: 0.047). When compared to the wild type, the combined variant form of Rad52/XRCC2/XRCC3 revealed an elevated risk of DTC (p value: 0.007). It is recommended that Rad52 2259C>T, XRCC2 R188H and XRCC3 T241M polymorphisms should be simultaneously considered as contributing to a polygenic risk of differentiated thyroid carcinoma.

Association between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: a Meta Analysis of 5,193 Cases and 6,645 Controls

  • Namazi, Abolfazl;Abedinzadeh, Maryam;Nourbaksh, Parisa;Neamatzadeh, Hossein
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2263-2268
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    • 2015
  • Background: Many studies have reported associations of the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism with colorectal cancer (CRC) risk, but the results remained controversial. Hence, we performed the present meta-analysis with different inheritance models. Materials and Methods: We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3 Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally included into the meta-analysis. Results: We found that the XRCC3 Thr241Met polymorphism was associated with increased CRC risk only under a dominant genetic model (CC+CT vs. TT: OR 0.575, 95%CI 0.498-1.665, p<0.001, $P_{heterogeneity}=0.00$, $I^2=83%$). There was a significant association between XRCC3 Thr241Met polymorphism and CRC risk in Caucasian in the overall 8 studies under only in the heterozygote genetic model (CT vs. TT: OR=0.929, 95%CI =0.806-1.070, P=0.308, $P_{heterogeneity}=0.002$, $I^2=57%$). Four studies evaluated the XRCC3 Thr241Met polymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantly correlated with increasing risk in Asians (dominant model: CC+CT vs. TT: OR= 0.609, 95%CI=411-0.902, P=0.013, $P_{heterogeneity}=0.54$, $I^2=0.00%$; Allele model: C vs. T: OR=0.708, 95 %=CI 0.605-0.829, p=0.000, $P_{heterogeneity}=0.000$, $I^2=92%$). The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. Conclusions: In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increased CRC risk, particularly in Asians rather than Caucasians.

Polymorphisms of XRCC1 and XRCC2 DNA Repair Genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India

  • Singh, Seram Anil;Ghosh, Sankar Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2811-2819
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    • 2016
  • Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.

XRCC3 Thr241Met Gene Polymorphism and Risk of Colorectal Cancer in Kashmir: a Case Control Study

  • Nissar, Saniya;Sameer, Aga Syed;Lone, Tufail A.;Chowdri, Nissar A.;Rasool, Roohi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9621-9625
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    • 2014
  • XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC ($p{\leq}0.05$). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p = 0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.