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

Publication ,  Journal Article
Li, H; Dai, H; Shi, T; Cheng, X; Sun, M; Chen, K; Wang, M; Wei, Q
Published in: Carcinogenesis
September 24, 2020

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.

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Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

September 24, 2020

Volume

41

Issue

9

Start / End Page

1229 / 1237

Location

England

Related Subject Headings

  • Transcription Factors
  • ROC Curve
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Platinum
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Genotype
 

Citation

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Li, H., Dai, H., Shi, T., Cheng, X., Sun, M., Chen, K., … Wei, Q. (2020). Potentially functional variants in nucleotide excision repair pathway genes predict platinum treatment response of Chinese ovarian cancer patients. Carcinogenesis, 41(9), 1229–1237. https://doi.org/10.1093/carcin/bgaa075
Li, Haoran, Hongji Dai, Tingyan Shi, Xi Cheng, Menghong Sun, Kexin Chen, Mengyun Wang, and Qingyi Wei. “Potentially functional variants in nucleotide excision repair pathway genes predict platinum treatment response of Chinese ovarian cancer patients.Carcinogenesis 41, no. 9 (September 24, 2020): 1229–37. https://doi.org/10.1093/carcin/bgaa075.
Li, Haoran, et al. “Potentially functional variants in nucleotide excision repair pathway genes predict platinum treatment response of Chinese ovarian cancer patients.Carcinogenesis, vol. 41, no. 9, Sept. 2020, pp. 1229–37. Pubmed, doi:10.1093/carcin/bgaa075.
Li H, Dai H, Shi T, Cheng X, Sun M, Chen K, Wang M, Wei Q. 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.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

September 24, 2020

Volume

41

Issue

9

Start / End Page

1229 / 1237

Location

England

Related Subject Headings

  • Transcription Factors
  • ROC Curve
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Platinum
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Genotype