摘要
目的鼻咽癌是由遗传和环境因素交互作用形成的多基因遗传疾病。本研究探讨端粒酶反转录酶和唇腭裂跨膜1样蛋白(telomerase reverse transcriptase,cleft lip and palate transmembrane-like protein 1,TERT-CLPTM1L)基因区域多态性与海南地区鼻咽癌患病风险关联性。方法采用病例-对照研究方法,选取2018-01-01-2018-06-30在海南医学院第一附属医院就诊的65例鼻咽癌患者作为病例组,选取同期常规体检的88名健康体检者作为对照组。通过多重单碱基延伸反应(SNaPshot SNP分型技术)检测TERT-CLPTM1L基因区域中rs33954691、rs13172201、rs6554743、rs2736100、rs2736098、rs2736106、rs2853668、rs401681和rs74739441位点基因型,各位点与鼻咽癌患病风险关系采用多因素二元Logistic回归分析。结果 9个单核苷酸多态性(single nucleotide polymorphism,SNP)位点中,rs2736098等位基因T(OR=2.669,95%CI=1.490～4.783,P=0.001)增加鼻咽癌患病风险,而rs401681等位基因T(OR=0.475,95%CI=0.257～0.877,P=0.017)降低患病风险。比较各位点基因型频率,rs33954691位点AA基因型(OR=3.911,95%CI=1.031～14.837,P=0.045)、rs2736098位点CT(OR=4.281,95%CI=1.456～12.585,P=0.008)和TT基因型(OR=13.584,95%CI=3.053～60.441,P=0.001)及rs2736106位点TC基因型(OR=4.627,95%CI=1.128～18.980,P=0.033)增加鼻咽癌患病风险,而rs401681位点TT基因型(OR=0.124,95%CI=0.022～0.693,P=0.017)降低患病风险。显性模型(OR=4.670,95%CI=1.129～19.320,P=0.033)下rs2736106等位基因C增加鼻咽癌患病风险;加性(OR=6.064,95%CI=1.256～29.290,P=0.025)、隐性(OR=4.128,95%CI=1.323～12.877,P=0.015)和显性模型(OR=4.898,95%CI=1.719～13.975,P=0.003)下rs2736098等位基因T皆增加患病风险;加性(OR=0.016,95%CI=0.002～0.162,P<0.001)、隐性(OR=0.196,95%CI=0.039～0.983,P=0.048)和显性模型(OR=0.396,95%CI=0.161～0.972,P=0.043)下rs401681等位基因T皆降低患病风险。结论TERT-CLPTM1L基因区域rs33954691、rs2736098、rs2736106和rs401681位点多态性与鼻咽癌患病风险有关联,但尚需扩大样本验证。
OBJECTIVE Nasopharyngeal carcinoma(NPC)is a polygenic genetic disease formed by the interaction of genetic and environmental factors.This study was designed to investigate the association between genetic polymorphism in TERT-CLPTMIL and risk of NPC.METHODS A total of 65 NPC patients(case group)and 88 healthy controls(control group)were enrolled from January 1,2018 to June 30,2018 in the First Affiliated Hospital of Hainan Medical College.The genotypes of rs33954691,rsl3172201,rs6554743,rs2736100,rs2736098,rs273610,rs2853668.rs401681and rs7473944 were detected by SNaPshot SNP typing,and the association between SNPs with NPC was evaluated by SPSS 22.0.RESULTS By comparing the allele frequencies of SNPs,the allele"T"of rs2736098 was significantly associated with increased risk of NPC(OR=2.669,95%CI=1.490-4.783,P=0.001)and the allele“T”of rs401681 was correlated to decreased risk of NPC(OR=0.475,95%CI=0.257-0.877,P=0.017).By comparing the genotype frequencies of SNPs,AA genotype of rs33954691(OR=3.911,95%CI=1.031-14.837,P=0.045),CT and TT genotypes of rs2736098(OR=4.281,95%CI=1.456-12.585,P=0.008;OR=13.584,95%CI=3.053-60.441,P=0.001),TC genotype of rs2736106 increased the risk of NPC(OR=4.627,95%CI=1.128-1&980,P=0.033);in contrast,TT genotype of rs401681 decreased the risk of NPC(OR=0.124,95%CI=0.022-0.693,P=0.017).In the genetic model analysis,the allele"C”of rs2736106 increased the risk of NPC under dominant model(OR=4.670,95%CI=l.129-19.320,P=0.033).Under additive,recessive and dominant models,the allele"T"of rs2736098 increased the risk of NPC(OR=6.064,95%CI=1.256-29.290,P=0.025;OR=4.128,95%CI=1.323-12.877,P=0.015;OR=4.898,95%CI=1.719-13.975,P=0.003),and the allele"T"of rs401681 decreased the risk of NPC(OR=0.016,95%CI=0.002-0.162,P<0.001;OR=0.196,95%CI=0.039-0.983,P=0.048;OR=0.396,95%CI=0.161-0.972,P=0.043).CONCLUSION The genetic polymorphisms of rs33954691,rs2736098,rs273610,and rs401681 in TERT-CLPTMIL were related with the risk of NPC,However,it still needs to be validated by enlarging the sample size.
作者
周平
林冰
张爽
王鹏
陈伟思
杨屏
林仙桃
程少文
刘沙
ZHOU Ping;LIN Bing;ZHANG Shuang;WANG Peng;CHEN Wei-si;YANG Ping;LIN Xian-tao;CHENG Shao-wen;LIU Sha(First Affiliated Hospital of Hainan Medical University,Haikou 570102.P.R.China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2019年第4期205-211,共7页
Chinese Journal of Cancer Prevention and Treatment
基金
海南省卫生计生行业科研项目(18A200027)
海南省自然科学基金(818MS140)
