Prediction of a side effect and efficacy of adjuvant chemotherapy with gemcitabine for post operative patient of pancreatic cancer by a genetic polymorphism analysis

Background/Aims: Single nucleotide polymorphism (SNP) of the genes for ATP-binding cassette transporters is related to the side effects of anticancer drugs and that of drug metabolism-related enzyme genes is involved in the activation of gemcitabine (GEM). Methodology: Forty eight patients treated with adjuvant GEM chemotherapy after pancreatic cancer resection was examined for the SNP of multidrug-resistance 1 (MDR1) 2677, MDR1 3435, breast cancer resistance protein (BCRP) 421, ribonucleotide reductase M1 (RRM1)(-)524, RRM1(-)37 and deoxycytidine deaminase (CDA) 208. We divided the patients according to normal group: patients homozygous for a wild-type allele or heterozygous for a mutant allele and mutant group: those homozygous for a mutant allele. Both groups were compared regarding the outcome and the occurrence and severity of side effects. Results: MDR1 2677, MDR1 3435, BCRP421, RRM1(-) 524, RRM1(-) 37 and CDA mutant groups comprised 37.5, 31.3, 0,12.5, 4.2 and 4.2%, respectively. The occurrence of ≥G3 side effects was the most frequent in the MDR1 2677 mutant group at 39%. The disease-free survival and overall survival tended to be longer in the MDR1 2677 mutant group. Conclusions: A correlation between the SNP of MDR1 2677 and drug response in patients receiving GEM chemotherapy.