title: A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis.
abstract: ATP-binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) genes, which are key players in the metabolism of many chemotherapeutic agents including those used in the treatment of lung cancer. We genotyped 53 polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small cell lung carcinoma (SCLC) and 206 cases of non-small cell lung carcinoma (NSCLC), and studied their impact on early response to chemotherapy, progression-free survival and overall survival. SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy but strongly with shorter progression-free survival and overall survival in SCLC but not NSCLC patients, indicating that ABCC2 genetic variation is an important factor in SCLC survival after chemotherapy.
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.forename: Phillip
authors.initials: P
authors.lastname: Müller
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Lena
authors.initials: L
authors.lastname: Knoefel
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Claus P
authors.initials: CP
authors.lastname: Heussel
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human