摘要目的 探讨中国新疆地区哈萨克族人群PLCE1基因rs2274223和rs3765524位点单核苷酸多态性与食管癌遗传易感性的关系.方法 采用病例-对照研究的方法,选择牧区哈萨克族食管癌患者(病例组)200例和正常者(对照组)300名,运用基质辅助激光解析电离时间飞行质谱(MALDI-TOF MS)的方法检测PLCE1基因rs2274223位点和rs3765524位点的单核苷酸多态性,应用非条件Logistic分析方法计算优势比(OR)及其95％可信区间(CI),评估不同基因型与食管癌发病风险及临床病理特征的关系.结果 rs2274223和rs3765524位点基因型的分布均符合Hardy-Weinberg平衡;rs2274223位点基因型及等位基因型在新疆哈萨克族食管癌病例组中的分布与对照组比较差异有统计学意义(P=0.006,P=0.003);Logistic回归分析表明,携带突变纯合型GG或只要携带突变位点G的个体(AG/GG)即可增加食管癌的罹患风险(GG比AA:OR =3.17,95％ CI=1.45 ～6.93;AG/GG比AA:OR=1.55,95％ CI=1.08 ～2.22);同时,凡是携带有rs2274223位点突变位点的个体罹患低分化食管癌(OR=2.48,95％ CI=1.10 ～5.60)且临床分期Ⅲ/Ⅳ期(OR=1.85,95％ CI=1.05 ～ 3.25)的风险大大增加.然而rs3765524位点基因型及等位基因在新疆哈萨克族食管癌病例组中的分布与对照组差异无统计学意义,且其与临床病理特征均未见相关性.结论携带PLCE1基因rs2274223位点可增加哈萨克族低分化食管癌的患病风险,且可以增加TNMⅢ/Ⅳ期食管癌的风险.

abstractsObjective To investigate the association between the rs2274223 and rs3765524 polymorphism of phospholipase C epsilon 1 (PLCE1) gene and the susceptibility to develop esophageal squamous cell carcinoma (ESCC) in a pure Kazakh Chinese population.Methods Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was utilized to genotype the potentially functional single nucleotide polymorphism rs2274223 A ＞ G and rs3765524 C ＞ T of PLCE1 in an ongoing hospital-based and case-control study of 200 ESCC cases with 300 cancer-free age (± 5 years) and sex matched controls.Statistical analyses were performed with Statistical Products and Services Solutions software (version 13.0).Adjusted odds ratios (OR) and 95％ confidence evaluation intervals (95％ CI) measured by multivariate logistic regression analysis were adopted to study the correlation of the gene polymorphism with the susceptibility to ESCC.Results The genotype frequencies observed for rs2274223 was consistent with Hardy-Weinberg equilibrium in controls.Univariate analysis revealed significant differences between cases and controls with respect to genotype distribution for rs2274223 (P =0.006).The variants of rs2274223 were found to confer significantly increased risk of ESCC (GG vs AA:OR =3.17,95％CI =1.45-6.93; AG/GG vs AA:OR =1.55,95％ CI =1.08-2.22) in the Kazakh Chinese population.Moreover,AG/GG genotype of rs2274223 was found to be significantly associated with poorlydifferentiated ESCC (OR =2.48,95％ CI =1.10-5.60).When the ESCC patients were divided into two subgroups,stage Ⅰ / Ⅱ and stage Ⅲ/Ⅳ according to the AJCC TNM classification,the GT/GG genotype of rs2274223 was significantly associated with stage Ⅲ/Ⅳ ESCC (OR =1.85,95％ CI =1.05-3.25).No significant association was found between rs3765524 and Kazakh ESCC.Conclusions These results indicate that rs2274223 site polymorphism of the PLCE1 gene is strongly associated with risk of ESCC in a Kazakh Chinese population,especially the poorly-differentiated and stage Ⅲ/Ⅳ ESCC.