Song Xingbo, Zhong Huiyu, Zhou Juan, Hu Xuejiao, Zhou Yi, Ye Yuanxin, Lu Xiaojun, Wang Jun, Ying Binwu, Wang Lanlan
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China, 610041.
Tumour Biol. 2015 Apr;36(4):2785-92. doi: 10.1007/s13277-014-2903-z. Epub 2014 Dec 4.
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.
在多种恶性肿瘤中均观察到整合素的高度表达。靶基因3'UTR区域中微小RNA结合位点的单核苷酸多态性（SNP）可能导致靶基因表达水平的改变，进而易患包括癌症在内的疾病。在本研究中，我们旨在探讨中国汉族人群中整合素基因微小RNA结合位点多态性与胃癌（GC）之间的关联。使用高分辨率熔解（HRM）分析对1000例GC患者和1000例无关对照进行了研究，检测整合素基因3'UTR区域微小RNA结合位点的5个SNP（ITGA3中的rs1062484 C/T、ITGA6中的rs17664 A/G、ITGB3中的rs3809865 A/T、ITGB4中的rs743554 C/T以及ITGB5中的rs2675 A/C）。SNP rs2675的多态性与GC易感性相关[比值比（OR）=0.52，95%置信区间（CI）=0.28 - 0.97，P = 0.028]。此外，rs2675的AA基因型和rs17664的GG基因型与1b期GC的发生几率较低相关[分别为OR = 0.39（0.18 - 0.85），P = 0.009；以及OR = 0.37（0.17 - 0.78），P = 0.004]；同样，rs17664的G等位基因频率与1b期肿瘤的发生几率较低相关[OR = 0.50（0.26 - 0.95），P = 0.021]。此外，rs3809865的AA基因型频率和A等位基因与4期GC的较高风险相关[分别为OR = 1.85（1.11 - 3.09），P = 0.012；以及OR = 1.52（0.99 - 2.33），P = 0.043]。对于rs17664，GG基因型和G等位基因似乎与伴有3b期淋巴转移的GC的较高风险相关[分别为OR = 1.76（1.00 - 3.11），P = 0.036；以及OR = 1.64（0.98 - 2.75），P = 0.048]。我们的数据表明，整合素3'UTR区域微小RNA结合位点的多态性与中国汉族人群的GC易感性（rs2675）、肿瘤分期（rs2675、rs17664和rs3809865）以及淋巴转移（rs17664）相关。
