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

Research paper by Kazuhiko K Kasuya, Akihiko A Tsuchida, Yuichi Y Nagakawa, Yoshiaki Y Suzuki, Minako M Suzuki, Tatsuya T Aoki, Yuta Y Abe, Motohide M Shimazu, Takao T Itoi, Atsushi A Sofuni

Indexed on: 14 Dec '11Published on: 14 Dec '11Published in: Hepato-gastroenterology



Abstract

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).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.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.A correlation between the SNP of MDR1 2677 and drug response in patients receiving GEM chemotherapy.

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