title: Association ofCHEK2polymorphisms with the efficacy of platinum-based chemotherapy for advanced non-small-cell lung cancer in Chinese never-smoking women.
abstract: BACKGROUND
  Cell cycle checkpoint kinase 2 (CHEK2) plays an essential role in the repair of DNA damage. Single nucleotide polymorphisms (SNPs) in DNA repair genes are thought to influence treatment effects and survival of cancer patients. This study aimed to investigate the relationship between polymorphisms in theCHEK2gene and efficacy of platinum-based doublet chemotherapy in never-smoking Chinese female patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Using DNA from blood samples of 272 Chinese advanced NSCLC non-smoking female patients treated with first-line platinum-based chemotherapy, we have analyzed the relationships between four SNPs in theCHEK2gene and clinical outcomes.
  
  
  RESULTS
  We found that overall survival (OS) was significantly associated withCHEK2rs4035540 (Log-Rank P=0.020), as well as theCHEK2rs4035540 dominant model (Log-Rank P=0.026), especially in the lung adenocarcinoma group. After multivariate analysis, patients with rs4035540 A/G genotype had a significantly better OS than those with the G/G genotype (HR =0.67, 95% CI, 0.48-0.93; P=0.016). In the toxicity analysis, it was observed that patients with theCHEK2rs4035540 A/A genotype had a higher risk of gastrointestinal toxicity than the G/G genotype group (P=0.009). However, there are no significant associations between chemotherapy treatments and genetic variations.
  
  
  CONCLUSIONS
  Our findings indicate that SNPs inCHEK2are related to Chinese advanced NSCLC never-smoking female patients receiving platinum-based doublet chemotherapy in China. Patients with rs4035540 A/G genotype have a better OS. And patients with rs4035540 A/A genotype have a higher risk of gastrointestinal toxicity. These results point to a direction for predicting the prognosis for Chinese never-smoking NSCLC female patients. However, there are no significant associations between chemotherapy treatments and SNPs inCHEK2, which need more samples to the further study.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Baohong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Xu
authors.affiliation: Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
keywords: Cell cycle checkpoint kinase 2 (CHEK2); chemotherapy; never-smoking women; non-small-cell lung cancer (NSCLC); single nucleotide polymorphisms (SNPs)