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. CONCLUSION: 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.
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. CONCLUSION: 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: Daniele Campa; Juan Sainz; Barbara Pardini; Ludmila Vodickova; Alessio Naccarati; Anja Rudolph; Jan Novotny; Asta Försti; Stephan Buch; Witigo von Schönfels; Clemens Schafmayer; Henry Völzke; Michael Hoffmeister; Bernd Frank; Roberto Barale; Kari Hemminki; Jochen Hampe; Jenny Chang-Claude; Hermann Brenner; Pavel Vodicka; Federico Canzian Journal: PLoS One Date: 2012-03-02 Impact factor: 3.240
Authors: Beata Mrozikiewicz-Rakowska; Marian Malinowski; Piotr Nehring; Joanna Bartkowiak-Wieczorek; Anna Bogacz; Ewa Żurawińska-Grzelka; Przemysław Krasnodębski; Jacek Muszyński; Tomasz Grzela; Adam Przybyłkowski; Leszek Czupryniak Journal: Arch Med Sci Date: 2019-09-26 Impact factor: 3.318
Authors: Douglas Vivona; Luciene Terezina Lima; Alice Cristina Rodrigues; Carolina Tosin Bueno; Greyce Kelly Steinhorst Alcantara; Luiza Saldanha Ribeiro Barros; Vania Tiestsche DE Moraes Hungria; Carlos Sérgio Chiattone; Maria DE Lourdes Lopes Ferrari Chauffaille; Elvira Maria Guerra-Shinohara Journal: Oncol Lett Date: 2014-02-07 Impact factor: 2.967
Authors: K Shitara; S Yuki; D Tahahari; M Nakamura; C Kondo; T Tsuda; T Kii; Y Tsuji; S Utsunomiya; D Ichikawa; A Hosokawa; A Ishiguro; D Sakai; S Hironaka; I Oze; K Matsuo; K Muro Journal: Br J Cancer Date: 2013-11-26 Impact factor: 7.640