title: Genome-wide Association Study on Platinum-induced Hepatotoxicity in Non-Small Cell Lung Cancer Patients.
abstract: Platinum-based chemotherapy has been shown to improve the survival of advanced non-small cell lung cancer (NSCLC) patients; the platinum-induced toxicity severely impedes the success of chemotherapy. Genetic variations, such as single nucleotide polymorphisms (SNPs), may contribute to patients' responses to the platinum-based chemotherapy. To identify SNPs that modify the risk of hepatotoxicity in NSCLC patients receiving platinum-based chemotherapy, we performed a genome-wide association scan in 334 subjects followed by a replication study among 375 subjects. Consistent associations with platinum-induced hepatotoxicity risk was identified for SNP rs2838566 located at 21q22.3, as the minor A allele could significantly increase the risk of liver injury (OR = 3.78, 95%CI = 1.99-7.19, P = 4.90 × 10(-5) for GWAS scan, OR = 1.89, 95%CI = 1.03-3.46, P = 0.039 for replication, and OR = 2.56, 95%CI = 1.65-3.95, P = 2.55 × 10(-5) for pooled population). These results suggested that genetic variants at 21q22.3 may contribute to the susceptibility of platinum-induced hepatotoxicity in NSCLC patients.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Songyu
authors.initials: S
authors.lastname: Cao
authors.affiliation: 1] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: 1] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Departments of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Thoracic Surgery, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: 1] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 1] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D003710:Demography; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000009:adverse effects* / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D010984:Platinum