An ERCC4 regulatory variant predicts grade-3 or -4 toxicities in patients with advanced non-small cell lung cancer treated by platinum-based therapy.
Abstract
Platinum-based chemotherapy (PBC) in combination with the 3rd generation drugs is
the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC);
however, the efficacy is severely hampered by grade 3-4 toxicities. Nucleotide excision
repair (NER) pathway is the main mechanism of removing platinum-induced DNA adducts
that contribute to the toxicity and outcome of PBC. We analyzed data from 710 Chinese
NSCLC patients treated with PBC and assessed the associations of 25 potentially functional
single nucleotide polymorphisms (SNPs) in nine NER core genes with overall, gastrointestinal
and hematologic toxicities. Through a two-phase study, we found that ERCC4 rs1799798
was significantly associated with overall and gastrointestinal toxicities [all patients:
GA/AA vs. GG, odds ratio (OR)adj =1.61 and 2.35, 95% confidence interval (CI)=1.11-2.33
and 1.25-4.41, and Padj =0.012 and 0.008, respectively]. Our prediction model for
the overall toxicity incorporating rs1799798 demonstrated a significant increase in
the area under the curve (AUC) value, compared to that for clinical factors only (all
patients: AUC = 0.61 vs. 0.59, 95% CI = 0.57-0.65 vs. 0.55-0.63, P = 0.010). Furthermore,
the ERCC4 rs1799798 A allele was associated with lower ERCC4 mRNA expression levels
according to the expression quantitative trait loci (eQTL) analysis. Our study provided
some new clue in future development of biomarkers for assessing toxicity and outcomes
of platinum drugs in lung cancer treatment.
Type
Journal articleSubject
HumansCarcinoma, Non-Small-Cell Lung
Lung Neoplasms
Gastrointestinal Diseases
Hematologic Diseases
Organoplatinum Compounds
DNA-Binding Proteins
DNA Adducts
RNA, Messenger
Antineoplastic Combined Chemotherapy Protocols
Computational Biology
DNA Repair
Polymorphism, Single Nucleotide
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Young Adult
Biomarkers, Tumor
Permalink
https://hdl.handle.net/10161/18516Published Version (Please cite this version)
10.1002/ijc.31153Publication Info
Zhang, Ruoxin; Jia, Ming; Xu, Yuan; Qian, Danwen; Wang, Mengyun; Zhu, Meiling; ...
Wei, Qingyi (2018). An ERCC4 regulatory variant predicts grade-3 or -4 toxicities in patients with advanced
non-small cell lung cancer treated by platinum-based therapy. International journal of cancer, 142(6). pp. 1218-1229. 10.1002/ijc.31153. Retrieved from https://hdl.handle.net/10161/18516.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info