Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer.
Abstract
CD133 is one of the most common stem cell markers, and functional single nucleotide
polymorphisms (SNPs) of CD133 may modulate its gene functions and thus cancer risk
and patient survival. We hypothesized that potentially functional CD133 SNPs are associated
with gastric cancer (GC) risk and survival. To test this hypothesis, we conducted
a case-control study of 371 GC patients and 313 cancer-free controls frequency-matched
by age, sex, and ethnicity. We genotyped four selected, potentially functional CD133
SNPs (rs2240688A>C, rs7686732C>G, rs10022537T>A, and rs3130C>T) and used logistic
regression analysis for associations of these SNPs with GC risk and Cox hazards regression
analysis for survival. We found that compared with the miRNA binding site rs2240688
AA genotype, AC + CC genotypes were associated with significantly increased GC risk
(adjusted OR = 1.52, 95% CI = 1.09-2.13); for another miRNA binding site rs3130C>T
SNP, the TT genotype was associated with significantly reduced GC risk (adjusted OR
= 0.68, 95% CI = 0.48-0.97), compared with CC + CT genotypes. In all patients, the
risk rs3130 TT variant genotype was significantly associated with overall survival
(OS) (adjusted P(trend) = 0.016 and 0.007 under additive and recessive models, respectively).
These findings suggest that these two CD133 miRNA binding site variants, rs2240688
and rs3130, may be potential biomarkers for genetic susceptibility to GC and possible
predictors for survival in GC patients but require further validation by larger studies.
Type
Journal articleSubject
gastric cancermicroRNA
polymorphism
stem cell
survival
AC133 Antigen
Antigens, CD
Case-Control Studies
Genetic Predisposition to Disease
Glycoproteins
Humans
MicroRNAs
Middle Aged
Peptides
Polymorphism, Single Nucleotide
Prognosis
Proportional Hazards Models
Risk Factors
Stomach
Stomach Neoplasms
Survival Analysis
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https://hdl.handle.net/10161/10665Published Version (Please cite this version)
10.1002/mc.22113Publication Info
Wang, Qiming; Liu, Hongliang; Xiong, Huihua; Liu, Zhensheng; Wang, Li-E; Qian, Ji;
... Wei, Qingyi (2015). Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify
susceptibility to and survival of gastric cancer. Mol Carcinog, 54(6). pp. 449-458. 10.1002/mc.22113. Retrieved from https://hdl.handle.net/10161/10665.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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