title: Association between polymorphisms of microRNA-binding sites in integrin genes and gastric cancer in Chinese Han population.
abstract: Highly elevated expression of integrin has been observed in a variety of malignant tumors. Single nucleotide polymorphisms (SNPs) in the microRNA-binding sites in the 3' UTR region of target genes may result in the level change of target gene expression and subsequently susceptible to diseases, including cancer. In this study, we aimed to investigate the association between polymorphisms of microRNA-binding sites of integrin genes and gastric cancer (GC) in Chinese Han population. Five SNPs of the microRNA-binding sites in the 3' UTR region of integrin genes (rs1062484 C/T in ITGA3, rs17664 A/G in ITGA6, rs3809865 A/T in ITGB3, rs743554 C/T in ITGB4, and rs2675 A/C in ITGB5) were studied using high resolution melting (HRM) analysis in 1000 GC patients and 1000 unrelated controls. The polymorphism of SNP rs2675 was associated with susceptibility of GC [odds ratio (OR) = 0.52, 95% confidence interval (CI) = 0.28-0.97, P = 0.028]. In addition, genotype AA of rs2675 and genotype GG of rs17664 were associated with a lower chance of GC at stage 1b [OR = 0.39 (0.18-0.85), P = 0.009; and OR = 0.37 (0.17-0.78), P = 0.004, respectively]; also, the frequency of allele G of rs17664 was associated with a lower chance of stage 1b tumor [OR = 0.50 (0.26-0.95), P = 0.021]. Furthermore, the frequency of genotype AA and allele A of rs3809865 were associated with a higher risk of stage 4 GC [OR = 1.85 (1.11-3.09), P = 0.012; and OR = 1.52 (0.99-2.33), P = 0.043, respectively]. For rs17664, GG genotype and allele G appeared to be associated with a higher risk with GC with lymphatic metastasis 3b [OR = 1.76 (1.00-3.11), P = 0.036; and OR = 1.64 (0.98-2.75), P = 0.048, respectively]. Our data suggest that polymorphisms of the microRNA-binding sites in the 3' UTR region of integrin are associated with GC susceptibility (rs2675), tumor stage (rs2675, rs17664, and rs3809865), and lymphatic metastasis (rs17664) in Chinese Han population.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China, 610041.
authors.forename: Xingbo
authors.initials: X
authors.lastname: Song
authors.forename: Huiyu
authors.initials: H
authors.lastname: Zhong
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Ye
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics*; D039503:Integrin alpha6 / Q000235:genetics*; D039641:Integrin beta Chains; D039661:Integrin beta3 / Q000235:genetics*; D039663:Integrin beta4 / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C000599264:ITGA3 protein, human; C588002:ITGA6 protein, human; C061248:ITGB3 protein, human; C059834:ITGB4 protein, human; C000599263:ITGB5 protein, human; D039422:Integrin alpha3; D039503:Integrin alpha6; D039641:Integrin beta Chains; D039661:Integrin beta3; D039663:Integrin beta4; D035683:MicroRNAs