锰超氧化物歧化酶基因C1183T、抵抗素基因启动子-420C/G单核苷酸多态性与吸烟的交互作用和食管鳞状细胞癌的关系

Interaction between single nucleotide polymorphism of manganese superoxide dismutase gene C1183T,resistin gene promoter-420C/G and cigarette smoking in esophageal squamous cell carcinoma

目的 探讨锰超氧化物歧化酶（MnSOD）基因C1183T、抵抗素基因启动子-420C/G单核苷酸多态性与吸烟的交互作用,以及与食管鳞状细胞癌（ESCC）的关系。方法 采用病例-对照研究的方法,选择经病理学检查确诊为原发性ESCC的患者720例（ESCC组）,对照组为进行健康体格检查者720名,并根据吸烟状况将研究对象分为不吸烟者和吸烟者（每天至少吸1支烟,持续半年以上）。以研究对象的外周血白细胞为样本,利用PCR分析MnSOD基因C1183T和抵抗素基因启动子-420C/G单核苷酸多态性。结果 ESCC组的吸烟者构成比显著高于对照组（OR=3.326 4,95%CI为1.907 5~5.740 6,P〈0.01）。ESCC组与对照组间C1183T的CC＋CT、TT基因型频率和C、T等位基因频率,以及-420C/G的CC＋CG、GG基因型频率和C、G等位基因频率的差异均有统计学意义（P值均〈0.01）。ESCC组C1183T的TT纯合子基因型和-420C/G的GG纯合子基因型频率分布分别为50.1%和49.9%,对照组分别为24.2%和23.9%。携带C1183T的TT纯合子基因型和-420C/G的GG纯合子基因型者罹患ESCC的风险显著增加（OR=3.155 3和3.168 3,95%CI分别为1.806 2~5.145 1和1.925 4-5.206 2）。基因突变的协同分析发现,ESCC组C1183T的TT纯合子基因型联合-420C/G的GG纯合子基因型者占39.7%,显著高于对照组的12.8%（P〈0.01）,携带两种纯合子基因型者罹患ESCC的风险显著增加（OR=5.065 1,95%CI为3.187 9~7.848 1）。吸烟与C1183T的TT纯合子基因型和-420C/G的GG纯合子基因型在ESCC的发生中均有交互作用（γ=3.926 6、3.938 3）。结论MnSOD基因C1183T的TT纯合子基因型、抵抗素基因启动子-420C/G的GG纯合子基因型和吸烟是ESCC的易患因素,基因多态性与吸烟的交互作用增加了ESCC的发病风险。

Objective To investigate the interaction between single nucleotide poiymorphisms of manganese superoxide dismutase （MnSOD） gene C1183T, resistin gene promoter -420C/G and cigarette smoking in esophageal squamous cell carcinoma （ESCC）. Methods A hospital-based 1 ： 1 matched case-control study was carried out in 720 patients pathologically diagnosed as ESCC and 720 healthy people. The ESCC cases and healthy controls were all divided into non-smokers and smokers, and the latter were identified based on the criteria of taking at least one cigarette each day for more than 6 months. Genetic polymorphisms of MnSOD gene C1183T and resistin gene promoter -420C/G were analyzed by polymerase chain reaction （PCR） technique in peripheral blood leukocytes of the subjects. Results The cigarette smoking rate of ESCC group was significantly higher than that in the control group （OR-3.326 4, 95%C/= 1. 907 5-5.740 6, P〈0.01. There were significant differences in the genotype frequencies of Cl183T （CC ＋ CT, TT and -420C/G （CC ＋ CG, GG） and allele frequencies of Cl183T （C, T） and -420C/G （C, G） （all P〈0.01）. The genotype frequencies of C1183T （TT） and -4200/G （GG） were 50.1% and 49.9% in ESCC patients, and were 24.2% and 23.9% in healthy controls respectively. The individuals who carried with O1183T （TT） or -4200/G （GG） had a higher risk of ESCC （OR = 3. 155 3, 95% Cl= 1. 806 2-5. 145 1 ; OR =3. 168 3, 95% CI= 1. 925 4-5.206 2）. Combined analysis of gene mutation showed that percentage of O1183T （TT）/-4200/G （GG） in ESCC group was significantly higher than that in control group （39.7 % vs. 12.8 %, P〈0.01 ）. The people who carried with O1183T （TT）/-4200/G （GG） had a high risk of ESCC （ OR = 5. 065 1, 95 % CI = 3. 187 9 - 7. 848 1 ）. Cigarette smoking was related to increased risk of ESCC in patients carrying 01183T （TT） and -4200/G （GG） （γ = 3. 926 6, 3. 938 3, respectively）. Conclusion MnSOD gene Ol183T （TT）, resistin gene promoter -4200/G （GG） and cigarette smoking are the risk factors of ESCC. The interaction between genetic polymorphism of Cl183T （TT）, -4200/G （GG） and cigarette smoking may increase the risk of ESCC. （Shanghai Med J, 2015, 38, 828-834）