Single-strand breaks （SSBs） can occur in cells either directly, or indirectly following initiation of base excision repair （BER）. SSBs generally have blocked termini lacking the conventional 5＇-phosphate and 3＇-...Single-strand breaks （SSBs） can occur in cells either directly, or indirectly following initiation of base excision repair （BER）. SSBs generally have blocked termini lacking the conventional 5＇-phosphate and 3＇-hydroxyl groups and require further processing prior to DNA synthesis and ligation. XRCC1 is devoid of any known enzymatic activity, but it can physically interact with other proteins involved in all stages of the overlapping SSB repair and BER pathways, including those that conduct the rate-limiting end-tailoring, and in many cases can stimulate their enzymatic activities. XRCC1^-/- mouse fibroblasts are most hypersensitive to agents that produce DNA lesions repaired by monofunctional glycosylase-initiated BER and that result in formation of indirect SSBs. A requirement for the deoxyribose phosphate lyase activity of DNA polymerase β （pol β） is specific to this pathway, whereas pol β is implicated in gap-filling during repair of many types of SSBs. Elevated levels of strand breaks, and diminished repair, have been demonstrated in MMS- treated XRCC1^-/-, and to a lesser extent in pol β^-/- cell lines, compared with wild-type cells. Thus a strong correlation is observed between cellular sensitivity to MMS and the ability of cells to repair MMS-induced damage. Exposure of wild-type and polβ^-/- cells to an inhibitor of PARP activity dramatically potentiates MMS-induced cytotoxicity. XRCC1^-/- cells are also sensitized by PARP inhibition demonstrating that PARP-mediated poly（ADP-ribosyl）ation plays a role in modulation of cytotoxicity beyond recruitment of XRCC 1 to sites of DNA damage.展开更多
AIM： TO evaluate the association between poly- morphisms XRCC1 Arg194Trp and Arg399GIn and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. METHODS： Geno...AIM： TO evaluate the association between poly- morphisms XRCC1 Arg194Trp and Arg399GIn and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. METHODS： Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis （CG） and 160 patients with gastric cancer （GC）, matched to 202 （Cl） and 150 （C2） controls, respectively. RESULTS： No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles （194Trp, 399Gin and 241Met） showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gin and XRCC3 241Met were related with gender, smoking, drinking and Hpylori infection in the CG and GC groups. CONCLUSION： Our results showed no evidence of a rela-tionship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilianpopulation, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer.展开更多
Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells wer...Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells were obtained from subjects including 140 HCC and 536 controls. The XRCC1 gene 399 codon polymorphism was detected by PCR-RFLP technique. Results: The frequency of XRCC1 399 Arg/Gln & Gln/Gln genotype in HCC patients (48.57%) was significantly higher that in normal controls (32.46%), and XRCC1 399 Arg/Gln & Gln/Gln genotype was associated with increased risk of HCC (adjusted odds ratios (OR)=2.18, 95% confidence interval (CI) 1.27～3.74). In addition, in the cohort of low/median level of AFB1 exposure, the codon 399 Gln allele was associated with a conspicuous significantly increasing risk for HCC (adjusted OR=2.06, 95% CI=1.01～4.20). Conclusion: The results indicate that the XRCC1 399 Gln allele is a potentially important determinant of susceptibility to AFB1-related HCC.展开更多
背景与目的:基因多态预测肿瘤化疗药物敏感性对肿瘤个体化治疗具有重要意义。本研究旨在探讨DNA修复基因XRCC1 codon194及399位点基因多态性与非小细胞肺癌长春瑞滨加顺铂(vinorelbine and cisplatin,NVB and DDP,NP)方案化疗敏感性的...背景与目的:基因多态预测肿瘤化疗药物敏感性对肿瘤个体化治疗具有重要意义。本研究旨在探讨DNA修复基因XRCC1 codon194及399位点基因多态性与非小细胞肺癌长春瑞滨加顺铂(vinorelbine and cisplatin,NVB and DDP,NP)方案化疗敏感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性技术检测164例非小细胞肺癌患者外周血DNAXRCC1194和399位点的多态性。选择NP方案化疗,化疗两周期后评价疗效,并分析化疗敏感性与基因多态性的关系。结果:携带XRCC1基因Codon194C/T+T/T基因型者化疗有效率(41.8%)是C/C基因型者(26.0%)的2.038倍(P=0.036,95%CI=1.044-3.976)。携带XRCC1基因Codon399G/G、A/G、A/A型的患者化疗有效率(37.1%,34.6%,14.3%)之间的差异无统计学意义(P>0.05)。展开更多
文摘Single-strand breaks （SSBs） can occur in cells either directly, or indirectly following initiation of base excision repair （BER）. SSBs generally have blocked termini lacking the conventional 5＇-phosphate and 3＇-hydroxyl groups and require further processing prior to DNA synthesis and ligation. XRCC1 is devoid of any known enzymatic activity, but it can physically interact with other proteins involved in all stages of the overlapping SSB repair and BER pathways, including those that conduct the rate-limiting end-tailoring, and in many cases can stimulate their enzymatic activities. XRCC1^-/- mouse fibroblasts are most hypersensitive to agents that produce DNA lesions repaired by monofunctional glycosylase-initiated BER and that result in formation of indirect SSBs. A requirement for the deoxyribose phosphate lyase activity of DNA polymerase β （pol β） is specific to this pathway, whereas pol β is implicated in gap-filling during repair of many types of SSBs. Elevated levels of strand breaks, and diminished repair, have been demonstrated in MMS- treated XRCC1^-/-, and to a lesser extent in pol β^-/- cell lines, compared with wild-type cells. Thus a strong correlation is observed between cellular sensitivity to MMS and the ability of cells to repair MMS-induced damage. Exposure of wild-type and polβ^-/- cells to an inhibitor of PARP activity dramatically potentiates MMS-induced cytotoxicity. XRCC1^-/- cells are also sensitized by PARP inhibition demonstrating that PARP-mediated poly（ADP-ribosyl）ation plays a role in modulation of cytotoxicity beyond recruitment of XRCC 1 to sites of DNA damage.
文摘AIM： TO evaluate the association between poly- morphisms XRCC1 Arg194Trp and Arg399GIn and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. METHODS： Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis （CG） and 160 patients with gastric cancer （GC）, matched to 202 （Cl） and 150 （C2） controls, respectively. RESULTS： No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles （194Trp, 399Gin and 241Met） showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gin and XRCC3 241Met were related with gender, smoking, drinking and Hpylori infection in the CG and GC groups. CONCLUSION： Our results showed no evidence of a rela-tionship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilianpopulation, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer.
基金This work was supported by the NationalNatural Science Foundation of China(No.39860032)
文摘Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells were obtained from subjects including 140 HCC and 536 controls. The XRCC1 gene 399 codon polymorphism was detected by PCR-RFLP technique. Results: The frequency of XRCC1 399 Arg/Gln & Gln/Gln genotype in HCC patients (48.57%) was significantly higher that in normal controls (32.46%), and XRCC1 399 Arg/Gln & Gln/Gln genotype was associated with increased risk of HCC (adjusted odds ratios (OR)=2.18, 95% confidence interval (CI) 1.27～3.74). In addition, in the cohort of low/median level of AFB1 exposure, the codon 399 Gln allele was associated with a conspicuous significantly increasing risk for HCC (adjusted OR=2.06, 95% CI=1.01～4.20). Conclusion: The results indicate that the XRCC1 399 Gln allele is a potentially important determinant of susceptibility to AFB1-related HCC.
文摘背景与目的:基因多态预测肿瘤化疗药物敏感性对肿瘤个体化治疗具有重要意义。本研究旨在探讨DNA修复基因XRCC1 codon194及399位点基因多态性与非小细胞肺癌长春瑞滨加顺铂(vinorelbine and cisplatin,NVB and DDP,NP)方案化疗敏感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性技术检测164例非小细胞肺癌患者外周血DNAXRCC1194和399位点的多态性。选择NP方案化疗,化疗两周期后评价疗效,并分析化疗敏感性与基因多态性的关系。结果:携带XRCC1基因Codon194C/T+T/T基因型者化疗有效率(41.8%)是C/C基因型者(26.0%)的2.038倍(P=0.036,95%CI=1.044-3.976)。携带XRCC1基因Codon399G/G、A/G、A/A型的患者化疗有效率(37.1%,34.6%,14.3%)之间的差异无统计学意义(P>0.05)。
