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.

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.

Objective: To explore the associations between genetic variations of glutathione synthetase gene (GSS) and response to platinum-based chemotherapy of small cell lung cancer(SCLC), and to analyze the influencing factors on survival. Methods: Four haplotype-tagging single nucleotide polymorphisms (htSNPs) of GSS were genotyped by Sequenom MassARRAY methods in 903 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were measured by odds ratios (OR) and 95% confidence intervals (CI), adjusted for sex, age, smoking, KPS, staging and chemotherapy regiments, by unconditional logistic regression model. The hazard ratios (HR) were estimated by Cox proportional hazards regression model. Results: Among the 903 patients, 462(51.2%) cases received cis-platinum and etoposide treatment while others were treated with carboplatin and etoposide. 656 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 25.0 months.We found that rs725521 located in the 3′ near gene region of GSS was significantly associated with chemotherapy response. Compared with the T allele, patients with C allele had a worse chemotherapy response and an increased risk of no-responders (P=0.027). Rs7265992 and rs725521 of GSS were associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy (HR=1.16, 95% CI=1.02-1.33, P=0.027; HR=1.17, 95% CI=1.05-1.31, P=0.006, respectively). The patients carrying 1 or 2 risk alleles and the patients carrying 3 or 4 risk alleles had worse MST than the patients without the rs7265992A and rs725521C risk alleles (24.0 and 22.0 versus 30.0 months), with the HR for death being 1.26 (95% CI=1.04-1.54) and with the HR of 1.52 (95%CI=1.18-1.97, P=0.001). Rs2025096 and rs2273684 were not associated with the OS of SCLC patients who received platinum-based chemotherapy. Age ≤ 56, KPS> 80, limited-stage, chemotherapy response and radiation therapy had a remarkably prolonged OS (all P<0.05). Conclusions These results suggest that GSS genetic polymorphism rs725521 plays an important role in the response to platinum-based chemotherapy, while rs7265992 and rs725521 have important effect on the prognosis of SCLC patients, which may be potential genetic biomarkers for personalized treatment of SCLC.