胸苷酸合成酶microRNA结合位点多态性与食管癌易感性和预后的关系  

Relationship of genetic polymorphisms in the microRNA binding-sites of the thymidylate synthase gene and risk and survival in esophagus cancer

作　　者：申蓉[1] 王瑜[2] 沙丹[1] 陈健鹏[1] 付国斌[1] 王彩霞[1] 

机构地区：[1]山东大学附属省立医院化疗科,山东济南250021 [2]山东大学附属省立医院放疗科,山东济南250021

出　　处：《中华肿瘤防治杂志》2015年第22期1726-1730,1734,共6页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的胸苷酸合成酶（thymidylate synthase，TS）在叶酸代谢和DNA合成与修复中起关键作用，本研究旨在探讨TS位于3′UTR的microRNA结合位点潜在功能性的单核苷酸多态性（single nucleotide polymorphism，SNP）与食管癌发病风险及其生存期的关系。方法收集2010—01—01—2015—02—28山东大学附属省立医院根据年龄和性别进行频数匹配的405例食管癌患者和420名健康对照进行病例对照研究，采用TaqMan方法检测筛选的rs16430 6bp del／ins、rs2790 A〉G和rs1059394 C〉T3个功能性TSSNP基因型，应用Logistic回归模型分析这些SNP与食管癌发病风险的关系，运用Cox比例风险模型分析其与食管癌生存期的关系。结果分析TS rs16430 6b pdel／ins，与0bp／0bp（OR=1．88，95％CI为1．23～2．97，P〈0．01）和隐性模型下0bp／0bp＋6bp／0bp（OR=1．74，95％CI为1．18～2．62，P〈0．01）基因型携带者比较，6bp／6bp基因型携带者发生食管癌的风险显著增高。分析TS rs2790 A〉G，与AA（OR=2．57，95％CI为1．29～5．32，P〈0．01）和隐性模型下AA＋AG（OR=2.54，95％CI为1．27～5．12，P〈0．01）基因型携带者比较，GG基因型携带者发生食管癌的风险明显增高。对于TS rs1059394 C〉T，CT基因型携带者（OR=1．66，95％CI为1．10～2．59，P〈0．05）和显性模型下TT＋CT基因型携带者（OR=1．58，95％CI为1．06～2．40，P〈0．05）比CC基因型携带者患食管癌的风险显著增高。根据年龄、性别、吸烟、饮酒及家族史分层分析，上述导致发病风险增高的基因型在几个亚组中差异均有统计学意义，P〈0．05。单体型分析中，T-G-6bp与C—G-6bp相比发生食管癌的风险明显增高，OR=1．36,95％CI为1．07～1．92，P〈0．05。这3个多态性对食管癌生存期均无明显影响。结论TS microRNA结合位点的3个SNP与食管癌发病风险明显相关，但与生存期无关，提示遗传因素在食管OBJECTIVE Thymidylate synthase （TS） plays a cricial role in folate metabolism and DNA synthesis and re pair. This study is to investigate the association between the potentially functional single nucleotide polymorphism （SNP） in the microRNA binding-sites of 3′UTR in the TS gene and esophagus cancer risk and survival. METHODS In the hospital-based case-control study of 405 esophagus cancer patients and 420 cancer-free controls in Shandong Provincial Hospital Affiliated to Shandong University from 2010-01-01 to 2015-02 28, frequency-matched by age and sex, we used the TaqMan methodology to genotype three selected functional TS SNP （rs16430 6bp del/ins,rs2790 A〉G and rs1059394 C〉T） and used logistic regression analysis for associations of these SNP with esophagus cancer risk and Cox proportional hazards regression analysis for survival. RESULTS Compared with the rs16430 0bp/0bp genotype （OR= 1.88,95% CI： 1.23-2.97, P〈0. 01） and 0bp/0bp-b 6bp/ 0bp g enotypes （OR= 1.74,95% CI = 1.18 - 2.62, P〈 0.01） under the recessive model, the 6bp/6bp genotype was associated with significantly increased esophagus cancer risk. For the TS rs2790A〉G,the GG genotype was associated with significantly increased esophagus cancer risk compared with the AA genotype （OR=2.57,95%CI=1. 29-5.32, P〈0.01） and the AA＋AG genotypes （OR=2.54,95%CI=1.27-5.12,P〈0.01） under the recessive model. For the TS rs1059394 C〉T,the CT geno type （OR=1. 66,95% CI=1. 10-2.59,P〈0.05） and the TT＋CT genotypes （OR=1. 58,95%CI= 1.06- 2.40,P〈0.05） under the dominant model were associated with significantly increased esophagus cancer risk compared with the CC genotype.According to age, sex, smoke, alcohol and family history in the stratified analysis, the increased risks remained statistically significant in the several subgroups （P〈0.05）. In the haplotype analysis,T-G-6bp was associated with significantly in- creased esophagus cancer risk compared with C-G-6bp （OR=1. 36,95%CI=1.07-1.92,P〈0.05）.

关 键 词：食管癌 多态性 胸苷酸合成酶 危险 生存 

分 类 号：R735.1[医药卫生—肿瘤]