AIM: Gemcitabine is the first chemotherapeutic agent to show clinical benefits in pancreatic cancer patients. While interindividual variability in chemoresponse is observed, genetic factors that affect drug metabolism have not been clearly defined. The purpose of this study is to evaluate the relationships between genetic polymorphisms and therapeutic efficacy in pancreatic cancer patients treated with gemcitabine. PATIENTS & METHODS: The study population consisted of 102 pancreatic cancer patients who had been treated with a gemcitabine-based chemotherapeutic regimen. 102 genetic polymorphisms were selected from 23 genes involved in the metabolism and action sites of gemcitabine and screened for polymorphisms using the MassARRAY(®) system. The polymorphisms and haplotypes were analyzed in relation to overall survival (OS), time-to-progression (TTP) and disease progression. RESULTS: CMPK1 360C>T was significantly associated with OS, TTP and disease progression (p = 0.042, 0.007 and 0.040, respectively, in a dominant genetic model). Additionally, CMPK1 240G>T was correlated with OS and TTP. The frequencies of the haplotypes for the CMPK1, SLC28A1, DCTD and TLE4 genes differed according to disease progression. CONCLUSION: Genetic polymorphisms in genes related to metabolism and action sites of gemcitabine showed associations with the therapeutic efficacy, in terms of OS, TTP and disease progression in pancreatic cancer patients treated with gemcitabine-based chemotherapy. In particular, polymorphisms of the CMPK1 gene seem to provide important prognostic information.
AIM: Gemcitabine is the first chemotherapeutic agent to show clinical benefits in pancreatic cancerpatients. While interindividual variability in chemoresponse is observed, genetic factors that affect drug metabolism have not been clearly defined. The purpose of this study is to evaluate the relationships between genetic polymorphisms and therapeutic efficacy in pancreatic cancerpatients treated with gemcitabine. PATIENTS & METHODS: The study population consisted of 102 pancreatic cancerpatients who had been treated with a gemcitabine-based chemotherapeutic regimen. 102 genetic polymorphisms were selected from 23 genes involved in the metabolism and action sites of gemcitabine and screened for polymorphisms using the MassARRAY(®) system. The polymorphisms and haplotypes were analyzed in relation to overall survival (OS), time-to-progression (TTP) and disease progression. RESULTS:CMPK1 360C>T was significantly associated with OS, TTP and disease progression (p = 0.042, 0.007 and 0.040, respectively, in a dominant genetic model). Additionally, CMPK1 240G>T was correlated with OS and TTP. The frequencies of the haplotypes for the CMPK1, SLC28A1, DCTD and TLE4 genes differed according to disease progression. CONCLUSION: Genetic polymorphisms in genes related to metabolism and action sites of gemcitabine showed associations with the therapeutic efficacy, in terms of OS, TTP and disease progression in pancreatic cancerpatients treated with gemcitabine-based chemotherapy. In particular, polymorphisms of the CMPK1 gene seem to provide important prognostic information.
Authors: Maria L Alvarellos; Jatinder Lamba; Katrin Sangkuhl; Caroline F Thorn; Liewei Wang; Daniel J Klein; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2014-11 Impact factor: 2.089
Authors: Ning Qing Liu; Christoph Stingl; Maxime P Look; Marcel Smid; René B H Braakman; Tommaso De Marchi; Anieta M Sieuwerts; Paul N Span; Fred C G J Sweep; Barbro K Linderholm; Anita Mangia; Angelo Paradiso; Luc Y Dirix; Steven J Van Laere; Theo M Luider; John W M Martens; John A Foekens; Arzu Umar Journal: J Natl Cancer Inst Date: 2014-01-07 Impact factor: 13.506
Authors: Ning Qing Liu; Tommaso De Marchi; Annemieke Timmermans; Anita M A C Trapman-Jansen; Renée Foekens; Maxime P Look; Marcel Smid; Carolien H M van Deurzen; Paul N Span; Fred C G J Sweep; Julie Benedicte Brask; Vera Timmermans-Wielenga; John A Foekens; John W M Martens; Arzu Umar Journal: Sci Rep Date: 2016-08-25 Impact factor: 4.379