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Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer—a case control study

机译:大肠癌同源重组修复RAD51,XRCC2和XRCC3基因多态性的病例对照研究

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摘要

XRCC2 and XRCC3 proteins are structurally and functionally related to RAD51 which play an important role in the homologous recombination, the process frequently involved in cancer transformation. In our previous work we show that the 135G>C polymorphism (rs1801320) of the RAD51 gene can modify the effect of the Thr241Met polymorphism (rs861539) of the XRCC3 gene. We tested the association between the 135G>C polymorphism of the RAD51 gene, the Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism (rs3218536) of the XRCC2 gene and colorectal cancer risk and clinicopathological parameters. Polymorphisms were evaluated by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) in 100 patients with invasive adenocarcinoma of the colon and in 100 sex, age and ethnicity matched cancer–free controls. We stratified the patients by genotypes, tumour Duke’s and TNM stage and calculated the linkage of each genotype with each stratum. Carriers of Arg188Arg/Me241tMet, His188His/Thr241Thr and His188His/G135G genotypes had an increased risk of colorectal cancer occurrence (OR 5.70, 95% CI 1.10–29.5; OR 12.4, 95% CI 1.63–94.9; OR 5.88, 95% CI 1.21–28.5, respectively). The C135C genotype decreased the risk of colorectal cancer singly (OR 0.06, 95% CI 0.02–0.22) as well as in combination with other two polymorphisms. TNM and Duke’s staging were not related to any of these polymorphisms. Our results suggest that the 135G>C polymorphism of the RAD51 gene can be an independent marker of colorectal cancer risk. The Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism of the XRCC2 gene can modify the risk of colorectal cancer.
机译:XRCC2和XRCC3蛋白与RAD51在结构和功能上相关,它们在同源重组中起着重要作用,而同源重组是癌症转化中经常涉及的过程。在我们以前的工作中,我们表明RAD51基因的135G> C多态性(rs1801320)可以修饰XRCC3基因的Thr241Met多态性(rs861539)的作用。我们测试了RAD51基因的135G> C多态性,XRCC3基因的Thr241Met多态性和XRCC2基因的Arg188His多态性(rs3218536)与结直肠癌风险和临床病理参数之间的关联。通过限制性片段长度多态性聚合酶链反应(RFLP-PCR)对100例结肠浸润性腺癌患者和100名性别,年龄和种族匹配的无癌对照进行了多态性评估。我们按照基因型,肿瘤Duke's和TNM分期对患者进行了分层,并计算了每种基因型与每个阶层的联系。 Arg188Arg / Me241tMet,His188His / Thr241Thr和His188His / G135G基因型的携带者发生结直肠癌的风险增加(OR 5.70,95%CI 1.10-29.5; OR 12.4,95%CI 1.63-94.9; OR 5.88,95%CI 1.21 –28.5)。 C135C基因型可单独降低结直肠癌的风险(OR 0.06,95%CI 0.02-0.22),并与其他两种多态性相结合。 TNM和Duke的分期与这些多态性均无关。我们的结果表明,RAD51基因的135G> C多态性可能是结直肠癌风险的独立标志。 XRCC3基因的Thr241Met多态性和XRCC2基因的Arg188His多态性可以改变结直肠癌的风险。

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