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[修复基因XPD751单核苷酸多态性与结直肠癌患者预后的关系]

[Relationship between single nucleotide polymorphism in repair gene XPD751 and prognosis in colorectal carcinoma patients].

作者信息

Chen Ya-min, Wu Xu-lan, Zhang Li-wei, Xu Xin, Liu Ji-wei

机构信息

Department of Oncology, the First Affiliated Hospital of Dalian Medical University, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2012 Jul;34(7):501-5. doi: 10.3760/cma.j.issn.0253-3766.2012.07.006.

DOI:10.3760/cma.j.issn.0253-3766.2012.07.006
PMID:22967467
Abstract

OBJECTIVE

To investigate whether single nucleotide polymorphism (SNP) in DNA repair gene XPD751 is associated with sensitivity and time to progression (TTP) for platinum-containing combination chemotherapy in advanced colorectal carcinoma.

METHODS

A total of 98 patients pathologically diagnosed as advanced colorectal cancer were treated with FOLFOX chemotherapy. TheDNA of peripheral blood-leukocytes was obtained before treatment, and XPD genetype was detected by PCR-RFLP analysis.

RESULTS

The frequency of XPD751 Lys/lys was 76 cases (77.6%), lys/Gln 17 cases (17.4%), and Gln/Gln genetype 5 cases (5.1%). The effective rate of FOLFOX chemotherapy among patients with XPD751 Lys/lys was 50.0%, lys/Gln 29.4%, and Gln/Gln genetypes 20.0%. The difference between Lys/lys and lys/Gln was statistically significant, χ(2) = 4.04, P < 0.05. The results indicated that the failure of chemotherapy in patients with Lys/Lys genetype was 3.8-fold to those with Lys/Gln, by adjusting of gender, age, and tumor metastasis (OR = 3.800). The MTTP of the 98 patients was 10.1 months. The MTTP was 11.3 months for patients with Lys/Lys genotypes of XPD751 gene and 2.9 months for patients with Lys/Gln and Gln/Gln genotypes of XPD751 gene, the difference between Lys/Lys and at least one Gln was significant (P < 0.05).

CONCLUSIONS

Single nucleotide polymorphism of XPD751 correlates with the clinical response to FOLFOX chemotherapy. XPD751 genetic polymorphisms may be associated with TTP of advanced colorectal carcinoma patients treated with oxaliplatin as the first line chemotherapy. XPD751 genotype detected by the PCR-RFLP method may be a predictor of prognosis for FOLFOX chemotherapy.

摘要

目的

探讨DNA修复基因XPD751中的单核苷酸多态性(SNP)是否与晚期结直肠癌含铂联合化疗的敏感性及疾病进展时间(TTP)相关。

方法

98例经病理诊断为晚期结直肠癌的患者接受FOLFOX化疗。治疗前采集外周血白细胞DNA,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)检测XPD基因类型。

结果

XPD751 Lys/Lys基因型76例(77.6%),Lys/Gln基因型17例(17.4%),Gln/Gln基因型5例(5.1%)。XPD751 Lys/Lys基因型患者FOLFOX化疗有效率为50.0%,Lys/Gln基因型为29.4%,Gln/Gln基因型为20.0%。Lys/Lys与Lys/Gln之间差异有统计学意义,χ² = 4.04,P < 0.05。结果表明,校正性别、年龄和肿瘤转移因素后,Lys/Lys基因型患者化疗失败的风险是Lys/Gln基因型患者的3.8倍(OR = 3.800)。98例患者的中位TTP为10.1个月。XPD751基因Lys/Lys基因型患者的中位TTP为11.3个月,Lys/Gln和Gln/Gln基因型患者为2.9个月,Lys/Lys与至少含有一个Gln的基因型之间差异有统计学意义(P < 0.05)。

结论

XPD751单核苷酸多态性与FOLFOX化疗临床反应相关。XPD751基因多态性可能与以奥沙利铂为一线化疗的晚期结直肠癌患者的TTP有关。采用PCR-RFLP方法检测的XPD751基因型可能是FOLFOX化疗预后的一个预测指标。

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