Association between polymorphisms in CTR1, CTR2, ATP7A, and ATP7B and platinum resistance in epithelial ovarian cancer.

Abstract

The copper transporters <italic>CTR1</italic>, <italic>CTR2</italic>, <italic>ATP7A</italic>, and <italic>ATP7B</italic> regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in <italic>CTR1</italic>, <italic>CTR2</italic>, <italic>ATP7A</italic>, and <italic>ATP7B</italic> on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in <italic>CTR1, CTR2, ATP7A</italic>, and <italic>ATP7B</italic> were genotyped in these patients. The <italic>CTR1</italic> rs10981694 polymorphism was observed to be associated with carboplatin resistance, while patients with the rs10981694 G allele showed a significantly higher rate of carboplatin resistance (OR = 4.00, 95% CI 1.309 - 12.23, p < 0.01). In addition, we found that <italic>ATP7A</italic> rs2227291 was associated with cisplatin resistance and that carriers of the C allele were more sensitive to cisplatin (OR = 0.40, 95% CI: 0.17 - 0.94, p = 0.03). Our findings suggest that the <italic>CTR1</italic> and <italic>ATP7A</italic> genetic polymorphisms could affect platinum resistance. The <italic>CTR1</italic> and <italic>ATP7A</italic> genes might be considered a predictive marker for carboplatin and cisplatin resistance, respectively.
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• Authors: Tailin Li, Jingbo Peng, Feiyue Zeng, Keqiang Zhang, Jinyang Liu, Xi Li, Qianying Ouyang, Guo Wang, Liansheng Wang, Zhaoqian Liu, Yingzi Liu
• Journal: International journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 55 Issue 10 Pg. 774-780 (Oct 2017) ISSN: 0946-1965 [Print] Germany
• PMID: 28737129 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cation Transport Proteins
• Copper Transporter 1
• Organoplatinum Compounds
• SLC31 Proteins
• SLC31A1 protein, human
• SLC31A2 protein, human
• ATP7A protein, human
• ATP7B protein, human
• Copper-Transporting ATPases

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Ovarian Epithelial
• Cation Transport Proteins (genetics)
• Copper Transporter 1
• Copper-Transporting ATPases (genetics)
• Drug Resistance, Neoplasm (genetics)
• Female
• Humans
• Male
• Middle Aged
• Neoplasms, Glandular and Epithelial (drug therapy, genetics)
• Organoplatinum Compounds (therapeutic use)
• Ovarian Neoplasms (drug therapy, genetics)
• Polymorphism, Single Nucleotide (genetics)
• SLC31 Proteins