Okubo Masaaki, Tahara Tomomitsu, Shibata Tomoyuki, Yamashita Hiromi, Nakamura Masakatsu, Yoshioka Daisuke, Yonemura Joh, Kamiya Yoshio, Ishizuka Takamitsu, Nakagawa Yoshihito, Nagasaka Mitsuo, Iwata Masami, Arisawa Tomiyasu, Hirata Ichiro
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192;
Exp Ther Med. 2010 Nov;1(6):1035-1040. doi: 10.3892/etm.2010.154. Epub 2010 Sep 29.
Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) have been shown to be associated with susceptibility to several types of human cancer. We evaluated the association between three SNPs (rs11614913, rs2910164 and rs3746444) in pre-miRNAs (miR-196a2, miR-146a and miR-499) and various clinicopathological characteristics, including CpG island hypermethylation (CIHM) status and overall survival in gastric cancer (GC) patients. rs11614913 (T>C), rs2910164 (C>G) and rs3746444 (A>G) SNPs were genotyped in 127 GC patients. CIHM of p14, p16, DAP-kinase and CDH1 genes was determined by methylation-specific polymerase chain reaction in the cancer tissues. A significant marginal association was found between the rs11614913 CC genotype and polypoid or elevated type morphology in early-stage GC (OR=6.29, 95% CI 1.18-33.47, p=0.03). The rs2910164 CC and CG genotypes were associated with increased susceptibility to CIHM of DAP-kinase (CC+CG, OR=5.48, 95% CI 1.30-23.10, p=0.02; CC, OR=6.93, 95% CI 1.37-35.02, p=0.02; CG, OR=4.24, 95% CI 0.87-20.78, p=0.07). The 11614913 TT and TC genotypes were associated with a higher number of CIHM (no. of CIHM 0-1 vs. 2-4; TT+TC, OR=3.67, 95% CI 0.98-13.72, p=0.05; TC, OR=4.08, 95% CI 1.04-15.97, p=0.04). When the subjects were divided according to age group, the combined rs11614913 TT+TC genotype tended to be associated with worse overall survival than the CC genotype in patients younger than 65 years of age (p=0.05). The combined rs2910164 CG+GG genotype also tended to be associated with worse overall survival than the CC genotype in the same age group (p=0.09). It appears that rs11614913 and rs2910164 SNPs in pre-miRNAs (miR-196a2 and miR-146a) affect the clinicopathological characteristics of GC, including its morphological appearance, CIHM status and overall survival.
微小RNA（miRNA）中的常见单核苷酸多态性（SNP）已被证明与多种类型人类癌症的易感性相关。我们评估了前体miRNA（miR - 196a2、miR - 146a和miR - 499）中的三个SNP（rs11614913、rs2910164和rs3746444）与各种临床病理特征的关联，包括胃癌（GC）患者的CpG岛高甲基化（CIHM）状态和总生存期。对127例GC患者进行了rs11614913（T>C）、rs2910164（C>G）和rs3746444（A>G）SNP的基因分型。通过甲基化特异性聚合酶链反应测定癌组织中p14、p16、DAP激酶和CDH1基因的CIHM。发现rs11614913 CC基因型与早期GC中的息肉样或隆起型形态之间存在显著边缘关联（OR = 6.29，95% CI 1.18 - 33.47，p = 0.03）。rs2910164 CC和CG基因型与DAP激酶CIHM易感性增加相关（CC + CG，OR = 5.48，95% CI 1.30 - 23.10，p = 0.02；CC，OR = 6.93，95% CI 1.37 - 35.02，p = 0.02；CG，OR = 4.24，95% CI 0.87 - 20.78，p = 0.07）。11614913 TT和TC基因型与更高数量的CIHM相关（CIHM数量0 - 1与2 - 4相比；TT + TC，OR = 3.67，95% CI 0.98 - 13.72，p = 0.05；TC，OR = 4.08，95% CI 1.04 - 15.97，p = 0.04）。当根据年龄组划分受试者时，在年龄小于65岁的患者中，rs11614913 TT + TC联合基因型的总生存期似乎比CC基因型更差（p = 0.05）。在同一年龄组中，rs2910164 CG + GG联合基因型的总生存期也似乎比CC基因型更差（p = 0.09）。前体miRNA（miR - 196a2和miR - 146a）中的rs11614913和rs2910164 SNP似乎会影响GC的临床病理特征，包括其形态外观、CIHM状态和总生存期。
