ERCC1 and ERCC2 variants predict survival in gastric cancer patients.
Abstract
PURPOSE: ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway
that effectively repairs DNA damage induced by chemotherapeutic agents. Therefore,
functional single nucleotide polymorphisms (SNPs) in these genes could have an impact
on clinical outcomes in cancer patients who received chemotherapy. However, few studies
have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes
in gastric cancer patients. EXPERIMENTAL DESIGN: We genotyped by the TaqMan assay
three common, potentially functional ERCC1 (rs3212986) and ERCC2 SNPs (rs13181 and
rs1799793) in 360 gastric cancer patients. We used both Kaplan-Meier tests and Cox
proportional hazards models to evaluate the effects of ERCC1 and ERCC2 genotypes and
haplotypes on clinical outcomes. RESULTS: We found that, compared with ERCC2 rs1799793
GG+AG genotypes, the homozygous variant AA genotype was associated with significantly
poorer overall survival (OS) (AA vs. GG+AG, log-rank P=0.012) and significantly higher
risk of death (AA vs. GG+AG, Adjusted hazards ratio [HR] 2.13; 95% CI, 1.28 to 3.56;
P=0.004). In combined analyses, patients with any one of the three unfavorable genotypes
(i.e. ERCC1 rs3212986 TT, ERCC2 rs13181 GG and rs1799793 AA) had statistically significant
hazards of poor prognosis (Adjusted HR, 1.54; 95% CI, 1.06 to 2.25; P=0.025), compared
with those without any unfavorable genotypes. Furthermore, the haplotype A-G-G (rs1799793/rs13181/rs3212986)
had a significant impact on OS (Adjusted HR, 1.57; 95% CI, 1.11 to 2.21; P=0.011),
compared with the common haplotype G-T-G. CONCLUSION: ERCC1 and ERCC2 functional SNPs
may jointly affect OS in Caucasian gastric cancer patients. Additional large prospective
studies are essential to confirm our findings.
Type
Journal articleSubject
HumansStomach Neoplasms
Endonucleases
DNA-Binding Proteins
Proportional Hazards Models
Haplotypes
Polymorphism, Single Nucleotide
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Xeroderma Pigmentosum Group D Protein
Young Adult
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https://hdl.handle.net/10161/18022Published Version (Please cite this version)
10.1371/journal.pone.0071994Publication Info
Li, Yangkai; Liu, Zhensheng; Liu, Hongliang; Wang, Li-E; Tan, Dongfeng; Ajani, Jaffer
A; & Wei, Qing-Yi (2013). ERCC1 and ERCC2 variants predict survival in gastric cancer patients. PloS one, 8(9). pp. e71994. 10.1371/journal.pone.0071994. Retrieved from https://hdl.handle.net/10161/18022.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.
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Show full item recordScholars@Duke
Zhensheng Liu
Assistant Professor of Medicine
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
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