Impact of the Copper Transporter Protein 1 (CTR1) Polymorphism on Adverse Events among Advanced NonSmall Cell Lung Cancer Patients Treated with a Carboplatin/Gemcitabine Regimen

Asian Pac J Cancer Prev. 2016;17(9):4391-4394.

Abstract

Background: Platinum-based regimens are effective treatments for advanced non-small cell lung cancer (NSCLC), but the five-year survival rate is still less than 20%. One possible factor appears to be resistance involving polymorphisms in the CTR1 gene which plays an importance role in accumulation of platinum in the cytoplasm.

Purpose: To establish both prevalence of CTR1 polymorphism and its impact on treatment related toxicity in Thai advanced NSCLC patients.

Materials and methods: Thirty-two advanced NSCLC participants received carboplatin and gemcitabine during January to June 2016 at King Chulalongkorn Memorial Hospital (KCMH) were recruited for analysis of the CTR1 rs12686377 genotype. These participants were planning to be treated with platinum-based chemotherapy for at least two cycles.

Results: Allele frequency of CTR1 polymorphism G?T was found to be 25%. The results showed that genetic polymorphism at CTR1 rs12686377 was associated with emesis side effects (P = 0.020) and neuropathic symptoms (P = 0.010). In addition, hematologic side effects in terms of anemia also tended to be related to this polymorphism.

Conclusions: This is the first study suggesting that polymorphism at CTR1 rs12686377 may be associated with toxicity from platinum-based regimens. Therefore, it could be a factor to aid in treatment decision-making.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cation Transport Proteins / genetics*
  • Copper Transporter 1
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Cation Transport Proteins
  • Copper Transporter 1
  • Organoplatinum Compounds
  • SLC31A1 protein, human
  • Deoxycytidine
  • Carboplatin
  • Gemcitabine