title: Effects of genetic polymorphisms in the ABCB1 gene on clinical outcomes in patients with gastric cancer treated by second-line chemotherapy.
abstract: OBJECTIVE
  Tumor cells that overexpress P-glycoprotein (Pgp) may be resistant to several anticancer agents due to altered pharmacokinetics and reduced intracellular concentrations of the anticancer agents. Pgp is encoded by the ATP binding cassette gene B1 (ABCB1). To our knowledge, only one previous report has evaluated the effect of ABCB1 gene polymorphisms on clinical outcomes of gastric cancer. The purpose of this analysis was to evaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advanced gastric cancer (AGC) treated with second-line chemotherapy.
  
  
  METHODS
  We retrospectively analyzed the impact of ABCB1 gene polymorphisms (ABCB1 3435C>T) on clinical outcomes in 100 patients with AGC who received second-line chemotherapy.
  
  
  RESULTS
  Median overall survival (OS) since the initiation of second-line chemotherapy was 6.0 months (95% confidence interval [CI], 4.8 to 8.0 months), and median progression-free survival (PFS) was 2.7 months (95% CI, 2.1 to 3.4 months). In a multivariate analysis of PFS, a 3435 CC polymorphism (n=45) was significantly associated with longer PFS compared with the CT/TT type polymorphism (n=55), with borderline significance (PFS of 3.2 months vs. 2.2 months, respectively; HR 1.50; 95% CI, 0.98-2.30; P = 0.061). ABCB1 3435 C>T polymorphisms were not associated with OS. No interaction was seen between ABCB1 polymorphisms and treatment regimens.
  
  
  CONCLUSIONS
  Genetic polymorphisms of ABCB1 3435C>T might have a possible impact on clinical outcomes of second-line chemotherapy in AGC. Further prospective evaluation using a larger sample size is required.
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Japan. Kouheis0824@yahoo.co.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawai
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yokota
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.forename: Takashi
authors.initials: T
authors.lastname: Shibata
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin