Acquired platinum resistance impedes successful treatment of epithelial ovarian cancer (EOC), and this resistance may be associated with inherited DNA damage-repair response. In the present study, we performed a two-phase analysis to assess associations between 8191 single-nucleotide polymorphisms (SNPs) within 127 genes of nucleotide excision repair (NER) pathway from a genome-wide association study (GWAS) dataset and platinum treatment response in 803 Han Chinese EOC patients. As a result, we identified that platinum-based chemotherapeutic response was associated with two potential functional variants MNAT1 rs2284704 T>C (TC+CC vs. TT, adjusted odds ratio (OR)=0.89, 95% confidence interval (CI)=0.83-0.95 and P=0.0005) and HUS1B rs61748571 A>G (AG+GG vs. AA, OR=1.10, 95% CI=1.03-1.18 and P=0.005). Compared to the prediction model for clinical factors only, models incorporating HUS1B rs61748571 (AUC 0.65 vs. 0.67, P=0.026) and the number of unfavorable genotypes (AUC 0.65 vs. 0.67, P=0.040) demonstrated a significant increase in the area under the curve (AUC). Further expression quantitative trait loci (eQTL) analysis suggested that MNAT1 rs2284704 T>C significantly influenced mRNA expression levels of MNAT1 (P=0.003). These results indicated that MNAT1 rs2284704 T>C and HUS1B rs61748571 A>G may serve as potential biomarkers for predicting platinum-treatment response of Chinese EOC patients, once validated by further functional studies.
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References

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