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XPD 和 ERCC1 多态性与结直肠癌预后的关系。

Polymorphisms in XPD and ERCC1 Associated with Colorectal Cancer Outcome.

机构信息

Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

出版信息

Int J Mol Sci. 2013 Feb 19;14(2):4121-34. doi: 10.3390/ijms14024121.

Abstract

Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and epidermal growth factor receptor (EGFR), were assessed in 257 postoperative stage II/III CRC patients with 5-fluorouracial chemotherapy in Taiwan. In addition, the correlations between genetic polymorphisms and patients' clinicopathological features were investigated. Genotypes of XPD codon751 A/A and ERCC1 codon118 T/T were associated with regional recurrence in a statistically significant way (p = 0.018). Patients who carried XPD AA and ERCC1 TT genotypes demonstrated a significantly greater regional recurrence risk (OR = 5.625, 95% CI, 1.557-20.32). Inherited variation in XPD and ERCC1 was associated with outcome in patients with colorectal cancer in Taiwan. As the significant association of single-nucleotide polymorphisms has not been studied previously in colorectal cancer, these findings suggest novel sites of variation, in part explaining the range of treatment responses seen in this disease.

摘要

采用综合方法选择多态性,我们旨在研究 DNA 修复和细胞增殖相关的三个基因的遗传变异是否与结直肠癌的复发有关。在台湾,对 257 例接受术后 II/III 期结直肠癌氟尿嘧啶化疗的患者进行了三种多态性(切除修复交叉互补基因 1(ERCC1)、着色性干皮病组 D(XPD)和表皮生长因子受体(EGFR))的评估。此外,还研究了遗传多态性与患者临床病理特征之间的相关性。XPD 密码子 751 A/A 和 ERCC1 密码子 118 T/T 基因型与局部复发呈显著相关(p = 0.018)。携带 XPD AA 和 ERCC1 TT 基因型的患者局部复发风险显著增加(OR = 5.625,95%CI,1.557-20.32)。XPD 和 ERCC1 的遗传变异与台湾结直肠癌患者的预后相关。由于在结直肠癌中以前没有研究过单核苷酸多态性的显著相关性,这些发现提示了该疾病治疗反应范围的部分解释的新的变异部位。

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