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

Autor:	Li H; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Dai H; Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China., Shi T; Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Fudan University Zhongshan Hospital, Shanghai, China., Cheng X; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.; Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China., Sun M; Department of Pathology, Tissue Bank, Fudan University Shanghai Cancer Center, Shanghai, China., Chen K; Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China., Wang M; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Wei Q; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.; Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.; Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA.
Jazyk:	angličtina
Zdroj:	Carcinogenesis [Carcinogenesis] 2020 Sep 24; Vol. 41 (9), pp. 1229-1237.
DOI:	10.1093/carcin/bgaa075
Abstrakt:	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. (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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