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

The copper transportersitalicCTR1/italic,italicCTR2/italic,italicATP7A/italic, anditalicATP7B/italicregulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms initalicCTR1/italic,italicCTR2/italic,italicATP7A/italic, anditalicATP7B/italicon 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) initalicCTR1, CTR2, ATP7A/italic, anditalicATP7B/italicwere genotyped in these patients. TheitalicCTR1/italicrs10981694 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 thatitalicATP7A/italicrs2227291 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 theitalicCTR1/italicanditalicATP7A/italicgenetic polymorphisms could affect platinum resistance. TheitalicCTR1/italicanditalicATP7A/italicgenes might be considered a predictive marker for carboplatin and cisplatin resistance, respectively. .