XPC基因多态性rs2228001对接受卡培他滨为基础辅助化疗的结直肠癌患者预后的影响

Implication of XPC rs2228001 polymorphism on the prognosis of patients with colorectal cancer who were treated with capecitabinebased adjuvant chemotherapy

目的:核苷酸切除修复是体内一种复杂的生化过程,参与了多种DNA损伤的修复。既往研究提示着色性干皮病基因组C(Xeroderma pigmentosum group C,XPC)基因在体内的DNA修复过程中发挥重要作用。本研究旨在探讨XPC基因多态性对接受卡培他滨为基础辅助化疗的结直肠癌(colorectal cancer,CRC)患者的预后影响。方法:连续性地纳入158例接受手术切除和卡培他滨为基础辅助化疗方案的CRC患者。回顾性整理分析患者的临床资料进行相关性分析。并用患者的外周血标本进行XPC基因遗传变异的分析和m RNA表达检测。探讨XPC基因多态性和预后及m RNA表达的关联性,通过Cox模型进行多变量校正。结果:本研究回顾性地整理分析并随访了158例接受卡培他滨为基础辅助化疗的CRC患者的生存数据,中位随访时间为5.0年(范围:0.25~7.5年)。158例CRC患者的中位无疾病生存期为4.5年,中位总生存期为5.7年。多态性分析结果提示rs2228001位点具有显著的临床意义。该位点在CRC患者中的分布频率为:TT基因型86例(54.4%),TG基因型60例(38.0%),GG基因型12例(7.6%),最小等位基因分布频率为0.27,符合哈迪温伯格平衡(P=0.733)。后续分析将TG和GG基因型合并,TT基因型和TG/GG基因型患者的中位无疾病生存期分别为4.5年和5.7年(χ^(2)=7.072,P=0.008)。此外,两组基因型患者的中位总生存期分别为5.0年和5.9年(χ^(2)=5.416,P=0.020)。另外,在65例可以检测XPC基因mRNA表达水平的患者中发现,TG/GG基因型的XPC基因的mRNA表达水平显著高于TT基因型,差异具有统计学意义(t=6.478,P<0.001)。结论:XPC基因rs2228001位点和接受卡培他滨为基础辅助化疗的CRC患者的预后有相关性。研究结论尚需要前瞻性研究进一步验证。

AIM:Nucleotide excision repair was a complex biochemical process that involved in the repair of many kinds of DNA damage.Previous study suggested that xeroderma pigmentosum group C(XPC)gene played an important role in the process of DNA damage repair.This study aimed to explore the influence of XPC gene polymorphism on the prognosis of patients with colorectal cancer(CRC)who were treated with capecitabine-related adjuvant chemotherapy.METHODS:A total of 158 patients with CRC who received surgical resection and capecitabine-based adjuvant chemotherapy were included in this study consecutively.Baseline clinical characteristics of patients were collected and analyzed.Additionally,peripheral blood specimens of the patients were collected for polymorphism analysis of XPC gene and mRNA expression of XPC,respectively.The association analysis between XPC polymorphism and prognosis and mRNA expression was performed.Cox regression analysis was used for multivariate adjustment.RESULTS:Prognostic data in the 158 patients with CRC who received capecitabine-based adjuvant chemotherapy was collected retrospectively.The median follow-up duration of the patients was 5.0 years(range:0.25-7.5 years).The median DFS and OS of the 158 patients with CRC was 4.5 years and 5.7 years,respectively.XPC polymorphism analysis suggested that rs2228001 was of clinical significance.The prevalence of rs2228001 polymorphism among CRC patients was:TT genotype 86 cases(54.4%),TG genotype 60 cases(38.0%)and GG genotype 12 cases(7.6%),resulting in a minor allele frequency of 0.27,which was in accordance with Hardy-Weinberg equilibrium(P=0.733).TG and GG genotypes were merged in the subsequent analysis.The prognostic results exhibited that the median DFS of patients with TT genotype and TG/GG genotype was 4.5 and 5.7 years,respectively(c2=7.072,P=0.008).Furthermore,the median OS of the two genotypes were 5.0 and 5.9 years(c2=5.416,P=0.020).Additionally,analysis of XPC gene mRNA expression in 65 specimens suggested that the mRNA expression of XPC in PBMC of the patients with TG/GG genotypes were significantly higher than that of the patients with TT genotype(t=6.478,P<0.001).CCONCLUSION:Polymorphism of rs2228001 in XPC gene was associated with prognosis of patients with CRC who received capecitabinebased adjuvant chemotherapy.And the conclusion should be confirmed in prospective clinical trials subsequently.