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. .