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

Hepatogastroenterology. 2012 Jul-Aug;59(117):1609-13. doi: 10.5754/hge11729.

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Chemotherapy, Adjuvant / adverse effects
  • Cytidine Deaminase / genetics
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Female
  • Gemcitabine
  • Genetic Testing
  • Heterozygote
  • Homozygote
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Pancreatectomy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / therapy*
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Ribonucleoside Diphosphate Reductase
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics

Substances

  • ABCB1 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antimetabolites, Antineoplastic
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • Deoxycytidine
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Cytidine Deaminase
  • Gemcitabine