title: Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients.
abstract: BACKGROUND
  Chemotherapy toxicity is a serious problem from which non-small cell lung cancer (NSCLC) patients suffer. The mismatch repair (MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patients. In this study, we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients.
  
  
  METHODS
  A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study. Toxicity was evaluated in each patient after two cycles of chemotherapy. A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy toxicity.
  
  
  RESULTS
  MutS homolog 2 (MSH2) rs6544991 [odds ratio (OR) 2.98, 95% confidence interval (CI) 1.20-7.40, P = 0.019] was associated with gastrointestinal toxicity in the dominant model; MSH3 rs6151627 (OR 2.38, 95% CI 1.23-4.60, P = 0.010), rs6151670 (OR 2.05, 95% CI 1.07-3.93, P = 0.031), and rs7709909 (OR 2.38, 95% CI 1.23-4.64, P = 0.010) were associated with hematologic toxicity in the dominant model. Additionally, MSH5 rs805304 was significantly associated with overall toxicity (OR 2.21, 95% CI 1.19-4.09, P = 0.012), and MSH5 rs707939 was significantly associated with both overall toxicity (OR 0.42, 95% CI 0.23-0.76, P = 0.004) and gastrointestinal toxicity (OR 0.44, 95% CI 0.20-0.96, P = 0.038) in the dominant model.
  
  
  CONCLUSIONS
  Genetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.
authors.affiliation: Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, P. R. China.
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors.forename: Chen-Yue
authors.initials: CY
authors.lastname: Qian
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Gao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China. yinjiye@csu.edu.cn.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, Hunan, P. R. China. yinjiye@csu.edu.cn.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, Hunan, P. R. China. yinjiye@csu.edu.cn.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D000074081:MutS Homolog 3 Protein; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C078444:MSH3 protein, human; C118481:MSH5 protein, human; D000074081:MutS Homolog 3 Protein; D016190:Carboplatin; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
keywords: Chemotherapy toxicity; DNA mismatch repair; Lung cancer; Platinum