Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, and Department of Surgical Oncology, N. Copernicus Hospital, Banacha 12/16, 90-237, Lodz, Poland.
Mol Biol Rep. 2011 Apr;38(4):2849-54. doi: 10.1007/s11033-010-0430-6. Epub 2010 Nov 20.
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.
XRCC2 和 XRCC3 蛋白在结构和功能上与 RAD51 相关，RAD51 在同源重组中发挥重要作用，而同源重组是癌症转化过程中经常涉及的过程。在我们之前的工作中，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。我们检测了 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）在 100 例侵袭性结肠癌患者和 100 例性别、年龄和种族匹配的无癌对照中评估了多态性。我们按基因型、肿瘤 Duke 分期和 TNM 分期对患者进行分层，并计算每个基因型与每个分层的连锁关系。Arg188Arg/Me241tMet、His188His/Thr241Thr 和 His188His/G135G 基因型携带者结直肠癌发生的风险增加（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 基因型单独（OR 0.06，95%CI 0.02-0.22）以及与其他两种多态性联合降低结直肠癌的风险。TNM 和 Duke 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物。XRCC3 基因的 Thr241Met 多态性和 XRCC2 基因的 Arg188His 多态性可以修饰结直肠癌的风险。
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