Chen J N, Feng T, Yang J, Li H M, Yuan P, Ma F, Yin L L, Lin D X, Xu B H, Tan W
State Key Laboratory of Molecular Oncology, Department of Etiology & Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2019 Feb 23;41(2):112-117. doi: 10.3760/cma.j.issn.0253-3766.2019.02.007.
To investigate the associations between genetic variations of DNA polymerase kappa (POLK) and treatment response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival. Five haplotype-tagging single nucleotide polymorphisms (htSNPs) of POLK were genotyped by Sequenom MassARRAY methods in 1 030 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between SNPs and treatment response were analyzed by computing the odds ratios () and 95% confidence intervals () from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios () and 95% . Among 1 030 cases, 558 (54.2%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Seven hundred and eighty eight patients were chemotherapy responders in the study with a response rate of 76.5%. The median follow-up time of these patients was 22.0 months. Patients were followed up to get their survival information. The median survival time of these patients was 22.5 months. Six hundred and seventy three patients (65.3%) had died by the last date of follow-up to get their survival information (Dec 21, 2017). Five htSNPs of POLK were not associated with the chemotherapy response of SCLC patients who received platinum-based chemotherapy (all >0.05). Multivariate Cox proportional hazards regression model analysis showed that, rs73120833 of POLK was significantly associated with the overall survival (OS) of SCLC patients, compared with POLK rs73120833 T allele, C allele can prolong OS (adjusted =0.87, 95% =0.77-0.97, =0.021). The remaining 4 SNPS, including rs10077427, rs3756558, rs4549504 and rs5744545, were not significantly associated with overall survival. Age≤56, KPS> 80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (all <0.05). These results suggest that POLK genetic polymorphism rs73120833 plays an important role on the prognosis of SCLC patients, which can be potential genetic biomarker for SCLC personalized treatment.
探讨DNA聚合酶κ（POLK）基因变异与小细胞肺癌（SCLC）铂类化疗疗效的相关性，并分析影响生存的因素。采用Sequenom MassARRAY方法对1030例接受铂类化疗、疗效和生存时间不同的SCLC患者进行POLK的5个单倍型标签单核苷酸多态性（htSNP）基因分型。通过逻辑回归模型计算比值比（OR）和95%置信区间（CI），分析SNP与治疗疗效的相关性。通过计算风险比（HR）和95%CI，采用Cox回归分析SNP与总生存的相关性。1030例患者中，558例（54.2%）接受顺铂联合依托泊苷治疗，其余接受卡铂联合依托泊苷治疗。研究中788例患者化疗有效，有效率为76.5%。这些患者的中位随访时间为22.0个月。对患者进行随访以获取生存信息。这些患者的中位生存时间为22.5个月。截至随访截止日期（2017年12月21日），673例患者（65.3%）死亡。POLK的5个htSNP与接受铂类化疗的SCLC患者的化疗疗效无关（均P>0.05）。多因素Cox比例风险回归模型分析显示，POLK的rs73120833与SCLC患者的总生存（OS）显著相关，与POLK rs73120833的T等位基因相比，C等位基因可延长OS（校正HR=0.87，95%CI=0.77-0.97，P=0.021）。其余4个SNP，包括rs1007
