Polymorphisms in the microRNA binding-site in the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer
Purpose-CD133 is one of the most common stem cell markers,and functional single nucleotide polymorphisms (SNP) of CD133 may modulate its gene functions and thus risk and survival of cancers.We hypothesized that potentially functional CD133 SNPs are associated with gastric cancer (GC) risk and survival.Method—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 functional CD133SNPs (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.Results—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,and the reduced risks remained statistically significant in the subgroup of <59 years,male,white,ever smokers,never drinker,and without family history (P <0.05).In all patients,the risk rs3130 TT variant genotype was significantly associated with OS (adjustedPtrend=0.016 and 0.007 under additive and recessive models,respectively).Conclusion—Two CD133 miRNA binding site variants,rs2240688 and rs3130,were potential biomarkers for genetic susceptibility to GC and possibly survival in GC patients.These findings require further validation by larger studies.
gastric cancer polymorphism stem cell survival microRNA
Qiming Wang Jaffer A. Ajani Qingyi Wei Hongliang Liu Huihua Xiong Zhensheng Liu Li-E Wang Ji Qian Ramya Muddasani Victoria Lu Dongfeng Tan
Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Ho Departments of Epidemiology The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, Departments of Epidemiology The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, Pathology The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
国内会议
重庆
英文
1-26
2013-10-01（万方平台首次上网日期，不代表论文的发表时间）