title: [Genetic variation in DNA repair gene RAD52 is associated with the response to platinum-based chemotherapy in SCLC patients].
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 (allP<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.
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: H M
authors.initials: HM
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: P
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: D K
authors.initials: DK
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: F
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: W W
authors.initials: WW
authors.lastname: Tan
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: T
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: D X
authors.initials: DX
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: B H
authors.initials: BH
authors.lastname: Xu
authors.affiliation: Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: W
authors.initials: W
authors.lastname: Tan
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics*; D012044:Regression Analysis; D012306:Risk; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin