title: 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.
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China; Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.forename: Huihua
authors.initials: H
authors.lastname: Xiong
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.forename: Ramya
authors.initials: R
authors.lastname: Muddasani
authors.forename: Victoria
authors.initials: V
authors.lastname: Lu
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics*; D016022:Case-Control Studies; D005753:Gastric Mucosa / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D010455:Peptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D035683:MicroRNAs; C000606023:PROM1 protein, human; D010455:Peptides
keywords: gastric cancer; microRNA; polymorphism; stem cell; survival