BACKGROUND: It has not been well established whether genetic variations can be biomarkers for clinical outcome of gemcitabine therapy. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) of gemcitabine metabolic and transporter genes that are associated with toxicity and efficacy of gemcitabine-based therapy in patients with locally advanced pancreatic cancer. METHODS: The authors evaluated 17 SNPs of the CDA,dCK, DCTD, RRM1, hCNT1-3, and hENT1 genes in 149 patients with locally advanced pancreatic cancer who underwent gemcitabine-based chemoradiotherapy. The association of genotypes with neutropenia, tumor response to therapy, overall survival, and progression-free survival (PFS) was analyzed by logistic regression, log-rank test, Kaplan-Meier plot, and Cox proportional hazards regression. RESULTS: The CDA A-76C, dCK C-1205T, RRM1 A33G, and hENT1 C913T genotypes were significantly associated with grade 3 to 4 neutropenia (P = .020, .015, .003, and .017, respectively).The CDA A-76C and hENT1 A-201G genotypes were significantly associated with tumor response to therapy (P = .017 and P = .019). A combined genotype effect of CDA A-76C, RRM1 A33G, RRM1 C-27A, and hENT1 A-201G on PFS was observed. Patients carrying 0 to 1 (n = 64), 2 (n = 50), or 3 to 4 (n = 17) at-risk genotypes had median PFS times of 8.3, 6.0, and 4.2 months, respectively (P = .002). CONCLUSIONS: The results indicated that some polymorphic variations of drug metabolic and transporter genes may be potential biomarkers for clinical outcome of gemcitabine-based therapy in patients with locally advanced pancreatic cancer.
BACKGROUND: It has not been well established whether genetic variations can be biomarkers for clinical outcome of gemcitabine therapy. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) of gemcitabine metabolic and transporter genes that are associated with toxicity and efficacy of gemcitabine-based therapy in patients with locally advanced pancreatic cancer. METHODS: The authors evaluated 17 SNPs of the CDA,dCK, DCTD, RRM1, hCNT1-3, and hENT1 genes in 149 patients with locally advanced pancreatic cancer who underwent gemcitabine-based chemoradiotherapy. The association of genotypes with neutropenia, tumor response to therapy, overall survival, and progression-free survival (PFS) was analyzed by logistic regression, log-rank test, Kaplan-Meier plot, and Cox proportional hazards regression. RESULTS: The CDAA-76C, dCKC-1205T, RRM1 A33G, and hENT1 C913T genotypes were significantly associated with grade 3 to 4 neutropenia (P = .020, .015, .003, and .017, respectively).The CDAA-76C and hENT1A-201G genotypes were significantly associated with tumor response to therapy (P = .017 and P = .019). A combined genotype effect of CDAA-76C, RRM1 A33G, RRM1C-27A, and hENT1A-201G on PFS was observed. Patients carrying 0 to 1 (n = 64), 2 (n = 50), or 3 to 4 (n = 17) at-risk genotypes had median PFS times of 8.3, 6.0, and 4.2 months, respectively (P = .002). CONCLUSIONS: The results indicated that some polymorphic variations of drug metabolic and transporter genes may be potential biomarkers for clinical outcome of gemcitabine-based therapy in patients with locally advanced pancreatic cancer.
Authors: Valeria Sebastiani; Francesca Ricci; Belen Rubio-Viqueira; Belen Rubio-Viquiera; Piotr Kulesza; Charles J Yeo; Manuel Hidalgo; Alison Klein; Daniel Laheru; Christine A Iacobuzio-Donahue Journal: Clin Cancer Res Date: 2006-04-15 Impact factor: 12.531
Authors: Scott N Myers; Rakesh K Goyal; Jennifer D Roy; Liane D Fairfull; John W Wilson; Robert E Ferrell Journal: Pharmacogenet Genomics Date: 2006-05 Impact factor: 2.089
Authors: Sara M Fitzgerald; Rakesh K Goyal; William R A Osborne; Jennifer D Roy; John W Wilson; R E Ferrell Journal: Hum Genet Date: 2006-01-31 Impact factor: 4.132
Authors: Elisa Giovannetti; Mario Del Tacca; Valentina Mey; Niccola Funel; Sara Nannizzi; Sergio Ricci; Cinzia Orlandini; Ugo Boggi; Daniela Campani; Marco Del Chiaro; Mauro Iannopollo; Generoso Bevilacqua; Franco Mosca; Romano Danesi Journal: Cancer Res Date: 2006-04-01 Impact factor: 12.701
Authors: James J Farrell; Hany Elsaleh; Miguel Garcia; Raymond Lai; Ali Ammar; William F Regine; Ross Abrams; A Bowen Benson; John Macdonald; Carol E Cass; Adam P Dicker; John R Mackey Journal: Gastroenterology Date: 2008-10-07 Impact factor: 22.682
Authors: E Giovannetti; A C Laan; E Vasile; C Tibaldi; S Nannizzi; S Ricciardi; A Falcone; R Danesi; G J Peters Journal: Nucleosides Nucleotides Nucleic Acids Date: 2008-06 Impact factor: 1.381
Authors: Sun Young Rha; Hei Cheul Jeung; Yeon Ho Choi; Woo Ick Yang; Jin Ho Yoo; Byung Soo Kim; Jae Kyung Roh; Hyun Cheol Chung Journal: Oncologist Date: 2007-06
Authors: Barbara Bournet; Marion Gayral; Jérôme Torrisani; Janick Selves; Pierre Cordelier; Louis Buscail Journal: World J Gastroenterol Date: 2014-08-21 Impact factor: 5.742
Authors: Congying Chen; Wenqin Xiao; Li Huang; Ge Yu; Jianbo Ni; Lijuan Yang; Rong Wan; Guoyong Hu Journal: Am J Transl Res Date: 2017-12-15 Impact factor: 4.060
Authors: Marelize Swart; Wesley M Stansberry; Victoria M Pratt; Elizabeth B Medeiros; Patrick J Kiel; Fei Shen; Bryan P Schneider; Todd C Skaar Journal: J Mol Diagn Date: 2019-02-20 Impact factor: 5.568