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: Xingbo Song, Huiyu Zhong, Juan Zhou, Xuejiao Hu, Yi Zhou, Yuanxin Ye, Xiaojun Lu, Jun Wang, Binwu Ying, Lanlan Wang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 4 Pg. 2785-92 (Apr 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25472585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ITGA3 protein, human
• ITGA6 protein, human
• ITGB3 protein, human
• ITGB4 protein, human
• ITGB5 protein, human
• Integrin alpha3
• Integrin alpha6
• Integrin beta Chains
• Integrin beta3
• Integrin beta4
• MicroRNAs

Topics

• Adult
• Aged
• Asian People (genetics)
• Binding Sites (genetics)
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Integrin alpha3 (genetics)
• Integrin alpha6 (genetics)
• Integrin beta Chains
• Integrin beta3 (genetics)
• Integrin beta4 (genetics)
• Lymphatic Metastasis
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Polymorphism, Single Nucleotide
• Stomach Neoplasms (genetics, pathology)