放化疗作用相关通路基因多态性与局部区域晚期鼻咽癌预后的关系

Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in locoregionally advanced nasopharyngeal carcinoma

目的:探讨放化疗作用相关通路基因多态性与初治局部区域晚期鼻咽癌患者预后的关系。方法:入组203例局部区域晚期鼻咽癌患者。检测属于放化疗通路或顺铂/氟尿嘧啶通路的13个基因、18个位点的单核苷酸多态性(SNP),采用Kaplan-Meier法进行生存分析,Cox回归进行多因素分析。结果:Kaplan-Meier分析显示,携带rs25487AA、rs1136410CC+TT基因型的患者总生存率降低;携带rs2032582AT基因型的患者无局部区域复发生存率降低;携带rs25487AA、rs2010963CC、rs833061CT+TT基因型的患者无远处转移生存率降低;携带rs3212986GG、rs25487AA、rs2032582AT、rs2279744GG+GT基因型的患者无进展生存率降低。Cox分析显示,上述位点除rs833061CT+TT基因型外,均为预后的独立危险因素(P<0.05)。结论:放化疗作用相关通路中的多个SNP是影响局部区域晚期鼻咽癌的独立预后因素,为鼻咽癌的个体化治疗和判断预后提供了参考指标。

OBJECTIVE：To investigate the correlation between the gene polymorphisms of radiotherapy,chemotherapy action pathways and the prognosis of the patients with locoregionally advanced nasopharyngeal carcinoma（NPC）.METHODS：A total of 203 locoregionally advanced NPC patients were enrolled in the study.18 single nucleotide polymorphisms（SNPs）belong to 13 genes in the radiotherapy and chemotherapy action pathways were examined.Kaplan-Meier method and Cox regression model were employed for analysis.RESULTS：Kaplan-Meier analysis showed that the patients carried rs25487 AA,rs1136410 CC＋TT genotypes had lower OS（overall survival rates）;the patients carried rs2032582 AT genotype had lower LRFS（locoregional relapse free survival rates）;the patients carried rs25487 AA,rs2010963 CC,rs833061 CT＋TT genotypes had lower DMFS（distant metastasis free survival rates）;the patients carried rs3212986 GG,rs25487 AA,rs2032582 AT,rs2279744 GG＋GT genotypes had lower PFS（progress free survival rates）.Cox analysis showed that the aforementioned SNPs were the independent influence factors to the correspondingly survival rates except rs833061（P〈0.05）.CONCLUSION：A few SNPs in radiotherapy or chemotherapy action pathways are prognostic factors for patients with locoregionally advanced NPC,which provided new molecular factors to evaluate the prognosis and perform individualized treatments.