title: The A/G allele of eIF3a rs3740556 predicts platinum-based chemotherapy resistance in lung cancer patients.
abstract: eIF3a is the largest subunit of eukaryotic translation initiation factor 3, which has been suggested to affect tumor progression and activity of nucleotide excision repair pathway contributing to platinum resistance. The purpose of this study was to investigate possible mutations in promoter and exon regions of eIF3a gene and to assess whether eIF3a mutation status have prognostic and predictive significance in platinum-based chemotherapeutic lung cancer patients. 771 lung cancer patients were enrolled and followed up. These patients were newly diagnosed with incident lung cancer, which was confirmed histologically or cytologically, and accepted platinum-based chemotherapy for at least two cycles. Three novel mutations of eIF3a were found, including 11279G>A in intron 6, Arg438Lys in exon 9, 29671G>A in intron 15, with minor allele frequency of 0.16, 0.18, 0.16, respectively. A-carrier patients of rs3740556 conferred a significantly better platinum-based chemotherapy response (p < 0.05) and seemed to live longer. eIF3a genetic polymorphisms can be considered as predictive tools for pretreatment evaluation of platinum-based chemotherapy. Lung cancer patients carrying rs3740556 A allele tended to have a favorable prognosis after treatment with platinum-based chemotherapy.
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan Province 410078, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.forename: Lifang
authors.initials: L
authors.lastname: Han
authors.forename: Huaping
authors.initials: H
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Duan
authors.forename: Boting
authors.initials: B
authors.lastname: Zhou
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhaoqian
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000225:Adenine; D000328:Adult; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D056726:Genetic Association Studies; D006147:Guanine; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D017671:Platinum Compounds / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D054316:Biomarkers, Pharmacological; C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; D017671:Platinum Compounds; D006147:Guanine; D000225:Adenine