Genetic variation in DNA repair gene RAD52 is associated with the response to platinum-based chemotherapy in SCLC patients
10.3760/cma.j.issn.0253-3766.2016.07.005
- VernacularTitle:DNA修复基因RAD52遗传变异与小细胞肺癌铂类药物化疗疗效的关系
- Author:
Hongmin LI
1
;
Peng YUAN
;
Dianke YU
;
Fei MA
;
Wenle TAN
;
Ting FENG
;
Jie YANG
;
Ying HUANG
;
Dongxin LIN
;
Binghe XU
;
Wen TAN
Author Information
1. 100021国家癌症中心,中国医学科学院北京协和医学院肿瘤医院病因及癌变研究室癌发生及预防分子机理北京市重点实验室
- Keywords:
Subject words] Small cell lung carcinoma;
Polymorphism,single nucleotide;
RAD52;
Platinum-based chemotherapy;
Response
- From:
Chinese Journal of Oncology
2016;38(7):504-509
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the associations between genetic variations of DNA repair gene RAD52 and response to platinum?based chemotherapy of small cell lung cancer ( SCLC) , and to analyze the influencing factors on survival. Methods Nine haplotype?tagging single nucleotide polymorphisms ( htSNPs) of RAD52 were genotyped by Sequenom Mass ARRAY technology in 939 SCLC patients who received platinum?based chemotherapy, and had different response and survival time. The associations between genotypes and platinum?based chemotherapy response were analyzed by odds ratios ( ORs) and 95%confidence intervals ( CIs) , adjusted for sex, age, smoking, KPS, staging and chemotherapy regimens, by unconditional logistic regression model. The relative ratios ( RRs ) were estimated using Cox proportional hazards regression model. Results Among the 939 cases, 483 ( 51. 4%) cases received cis?platinum and etoposide treatment while others treated with carboplatin and etoposide. Six hundred and eighty two patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time ( MST) of these patients was 25 months. We found that rs10774474 SNP which located in the 5′?flanking region of RAD52 was significantly associated with chemotherapy response. Compared with the TT genotype, patients with TA and AA genotype had a worse chemotherapy response and increased risk of no?response ( P=0. 004 ) . Correlation analysis showed that patients with KPS >80 had a better chemotherapy response than those with KPS≤80 (P=0.001). The patients with extensive?stage had a worse chemotherapy response than those with limited?stage (P<0.001). Cox proportional hazards regression model analysis showed that nine htSNPs of RAD52 were not associated with the overall survival ( OS) of SCLC patients who received platinum?based chemotherapy. Age≤56, KPS>80, limited?stage, chemotherapy response and radiation therapy can remarkably prolong OS ( all P<0.05) . Conclusions These results suggest that RAD52 genetic polymorphism rs10774474 plays an important role in the response to platinum?based chemotherapy, and may be a potential genetic biomarker for SCLC personalized treatment.
