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

Kazuhiko Kasuya, Akihiko Tsuchida, Yuichi Nagakawa, Yoshiaki Suzuki, Minako Suzuki, Tatsuya Aoki, Yuta Abe, Motohide Shimazu, Takao Itoi, Atsushi Sofuni

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1609-1613
Number of pages5
JournalHepato-Gastroenterology
Volume59
Issue number117
DOIs
Publication statusPublished - 2012 Jul
Externally publishedYes

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gemcitabine
Multiple Drug Resistance
Genetic Polymorphisms
Adjuvant Chemotherapy
Pancreatic Neoplasms
Ribonucleotide Reductases
Single Nucleotide Polymorphism
deoxycytidine deaminase
Alleles
ATP-Binding Cassette Transporters
Drug-Related Side Effects and Adverse Reactions
Pharmaceutical Preparations
Genes
Disease-Free Survival

Keywords

  • Gemcitabine
  • Multidrug-resistance 1
  • Pancreatic cancer
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Prediction of a side effect and efficacy of adjuvant chemotherapy with gemcitabine for post operative patient of pancreatic cancer by a genetic polymorphism analysis. / Kasuya, Kazuhiko; Tsuchida, Akihiko; Nagakawa, Yuichi; Suzuki, Yoshiaki; Suzuki, Minako; Aoki, Tatsuya; Abe, Yuta; Shimazu, Motohide; Itoi, Takao; Sofuni, Atsushi.

In: Hepato-Gastroenterology, Vol. 59, No. 117, 07.2012, p. 1609-1613.

Research output: Contribution to journalArticle

Kasuya, Kazuhiko ; Tsuchida, Akihiko ; Nagakawa, Yuichi ; Suzuki, Yoshiaki ; Suzuki, Minako ; Aoki, Tatsuya ; Abe, Yuta ; Shimazu, Motohide ; Itoi, Takao ; Sofuni, Atsushi. / Prediction of a side effect and efficacy of adjuvant chemotherapy with gemcitabine for post operative patient of pancreatic cancer by a genetic polymorphism analysis. In: Hepato-Gastroenterology. 2012 ; Vol. 59, No. 117. pp. 1609-1613.
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AU - Kasuya, Kazuhiko

AU - Tsuchida, Akihiko

AU - Nagakawa, Yuichi

AU - Suzuki, Yoshiaki

AU - Suzuki, Minako

AU - Aoki, Tatsuya

AU - Abe, Yuta

AU - Shimazu, Motohide

AU - Itoi, Takao

AU - Sofuni, Atsushi

PY - 2012/7

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N2 - 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.

AB - 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.

KW - Gemcitabine

KW - Multidrug-resistance 1

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KW - Single nucleotide polymorphism

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