Genetic variation in DNA polymerase kappa gene is associated with the prognosis after platinum-based chemotherapy in small cell lung cancer patients
10.3760/cma.j.issn.0253-3766.2019.02.007
- VernacularTitle: POLK基因遗传变异与小细胞肺癌患者铂类药物化疗后的生存相关
- Author:
Jinna CHEN
1
;
Ting FENG
1
;
Jie YANG
1
;
Hongmin LI
1
;
Peng YUAN
2
;
Fei MA
2
;
Luxi YIN
1
;
Dongxin LIN
1
;
Binghe XU
2
;
Wen TAN
1
Author Information
1. 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
2. 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
- Publication Type:Clinical Trail
- Keywords:
Small Cell Lung Carcinoma;
POLK;
Polymorphism, single nucleotide;
Platinum-based chemotherapy;
Response;
Prognosis
- From:
Chinese Journal of Oncology
2019;41(2):112-117
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.
Methods: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 (ORs) and 95% confidence intervals (CIs) from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios (HRs) and 95% CIs.
Results: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 P>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 HR=0.87, 95% CI=0.77-0.97, P=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 P<0.05).
Conclusion: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.
