title: Prediction of a side effect and efficacy of adjuvant chemotherapy with gemcitabine for post operative patient of pancreatic cancer by a genetic polymorphism analysis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
authors.affiliation: Department of Digestive Surgery, Tokyo Medical University, Tokyo, Japan. kasuya-k@jcom.home.ne.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kasuya
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nagakawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Minako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aoki
authors.forename: Yuta
authors.initials: Y
authors.lastname: Abe
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
authors.forename: Takao
authors.initials: T
authors.lastname: Itoi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sofuni
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003564:Cytidine Deaminase / Q000235:genetics; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012262:Ribonucleoside Diphosphate Reductase; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000093542:Gemcitabine
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D003564:Cytidine Deaminase; D000093542:Gemcitabine