Nemo样激酶基因多态性与结直肠癌遗传易感相关性  

Association of the Nemo-like kinase genetic polymorphism with risk of colorectal cancer

作　　者：周轶凡 陈婷婷[2] 程筱雯[1] Zhou Yifan;Chen Tingting;Cheng Xiaowen(Dept of Clinical Laboratory,The First Affiliated Hospital of Anhui Medical University, Heifei 230022;Dept of Pathology, Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学第一附属医院检验科,合肥230022 [2]安徽医科大学病理教研室,合肥230032

出　　处：《安徽医科大学学报》2019年第9期1467-1470,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81302150)

摘　　要：目的探讨Nemo样激酶(NLK)基因与结直肠癌(CRC)遗传易感性之间的关系。方法采用病例对照研究,选取55例CRC患者和50例健康对照,病例组和对照组按性别和年龄进行匹配。首先通过免疫组织化学评估CRC组织标本中NLK的表达情况,随后通过高分辨率熔解曲线法(HRM)对NLK基因的单核苷酸多态性(SNP)位点rs2125846(A/G)进行基因分型,使用Pearson χ^2检验和非条件Logistic回归分析rs2125846多态性与CRC易感性之间的关系。结果 CRC组织中NLK的表达水平高于相应的癌旁组织。病例组中rs2125846 AA、AG、GG基因型的频率分别为41.8%、58.2%和0%;相应的在对照组中分别为52.0%、36.0%和12.0%,两组之间差异有统计学意义(χ^2=9.888, P = 0.007 1 )。与AA基因型相比,携带AG基因型患CRC的 OR =2.01,95% CI :0.898~4.496,携带AG基因型发生CRC的风险是AA基因型的2.01倍。携带G等位基因(GG+AG)的患者发生CRC的风险是AA基因型的1.51倍( OR =1.51,95% CI :0.697~3.259)。在病例组中未检测到rs2125846与年龄、CRC主要发生部位及常见临床病理特征有统计学相关性。结论本研究鉴定了位于人类NLK基因内含子内新的CRC易感位点rs2125846。随后需要进一步扩大样本量(包括扩大种族和地理覆盖范围)及功能验证以确认NLK基因对CRC发生风险的影响。Objective To investigate the expression of Nemo-like kinase(NLK) in colorectal cancer (CRC) and the association of the NLK gene rs2125846 polymorphism with the susceptibility to CRC. Methods This case-control study enrolled 55 CRC cases and 50 controls in a Chinese population. Cases and controls were matched by gender and age. Expression of NLK in tissue specimens was assessed by immunohistochemistry. Single nucleotide polymorphisms (SNPs) were genotyped by high resolution melting (HRM) method. Pearson χ^2 test and Logistic regression were used for the association between SNPs and CRC. Results The expression level of NLK in cancer tissues was higher than that in adjacent tissues. The frequency of rs2125846 GG/AG/AA in the case group was 41.8%, 58.2%, and 0%, respectively;and 52.0%, 36.0%, and 12.0% in the control group, respectively. The difference between case and control group was statistically significant (χ^2=9.888, P = 0.007 1 ). Compared with the AA genotype, the GG/AG genotype increased the risk of colorectal cancer ( OR =2.01;95% CI :0.898~4.496). The AG genotype was 2.01 times more likely to develop cancer than the AA genotype. Cases carrying the G allele (GG+AG) were 1.51 times more likely to develop CRC than the AA genotype ( OR =1.51;95% CI :0.697~3.259). There was no statistically significant association between rs2125846 and age, major CRC sites, and common pathological features in the case group. Conclusion We identified a new susceptibility locus, rs2125846, for CRC risk located within intron of the human NLK gene in the Chinese population. Subsequent further functional verification and expanded racial and geographical coverage are needed to facilitate our understanding of this SNP in CRC.

关 键 词：结直肠癌 Nemo样激酶 基因多态性 基因易感性 

分 类 号：R735.3[医药卫生—肿瘤]