title: Genome-wide association study of myelosuppression in non-small-cell lung cancer patients with platinum-based chemotherapy.
abstract: Platinum-induced myelosuppression severely impedes successful chemotherapy in non-small-cell lung cancer (NSCLC) patients. Hence, it is clinically important to identify the patients who are at high risk for severe toxicity to certain chemotherapy. We first carried out a genome-wide scan of 906 703 single-nucleotide polymorphisms (SNPs) to identify genetic variants associated with platinum-induced myelosuppression risk in 333 NSCLC patients with chemotherapy. Then, we replicated 24 SNPs that had P<1 × 10(-4) in another independent cohort of 876 NSCLC patients. With P<0.05 as the criterion of statistical significance, we found that rs13014982 at 2q24.3 and rs9909179 at 17p12 exhibited consistently significant associations with myelosuppression risk in both the genome-wide association studies (GWAS) scan and the replication stage (rs13014982: odds ratio (OR)=0.55, 95% confidence intervals (CIs): 0.41-0.74, P=7.29 × 10(-5) for GWAS scan and OR=0.77, 95% CI: 0.65-0.93, P=0.006 for replication stage; rs9909179: OR=0.51, 95% CI: 0.37-0.70, P=4.60 × 10(-5) for GWAS scan and OR=0.82, 95% CI: 0.68-0.99, P=0.040 for replication stage; both in additive model). In combined samples of genome-wide scan and replication samples, the minor alleles of rs13014982 and rs9909179 remained significant associations with the decreased risk of myelosuppression (rs13014982: OR=0.71, 95% CI: 0.61-0.83, P =1.36 × 10(-5); rs9909179: OR=0.76, 95% CI: 0.65-0.89, P=0.001). Rs13014982 at 2q24.3 and rs9909179 at 17p12 might be independent susceptibility markers for platinum-induced myelosuppression risk in NSCLC patients.
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: S
authors.initials: S
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: S
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Departments of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Y
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: L
authors.initials: L
authors.lastname: Xu
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: R
authors.initials: R
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory Disease, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai, China, Shanghai, China.|6PromMed Cancer Centers, Shangai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.|Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai, China, Shanghai, China.|6PromMed Cancer Centers, Shangai, China.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Bai
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: G
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Shen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D044466:Asian People; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D055106:Genome-Wide Association Study; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D043823:Taxoids / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D006454:Hemoglobins; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine
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