Potentially functional variants in nucleotide excision repair pathway genes predict platinum treatment response of Chinese ovarian cancer patients

Carcinogenesis. 2020 Sep 24;41(9):1229-1237. doi: 10.1093/carcin/bgaa075.

Abstract

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 within 127 genes of nucleotide excision repair pathway from a genome-wide association study 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 potentially functional variants MNAT1 rs2284704 T>C [TC + CC versus 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 versus AA, OR = 1.10, 95% CI = 1.03-1.18 and P = 0.005). Compared with the prediction model for clinical factors only, models incorporating HUS1B rs61748571 [area under the curve (AUC) 0.652 versus 0.672, P = 0.026] and the number of unfavorable genotypes (AUC 0.652 versus 0.668, P = 0.040) demonstrated a significant increase in the AUC. Further expression quantitative trait loci 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Biomarkers, Tumor / genetics*
  • Cell Cycle Proteins / genetics*
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Platinum / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • ROC Curve
  • Transcription Factors / genetics*

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • HUS1B protein, human
  • MNAT1 protein, human
  • Transcription Factors
  • Platinum