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目的:探讨叶酸代谢相关基因MTHFR、CBS和肿瘤密切相关基因MGMT、P16、FHIT、RASSF1A甲基化状态与哈萨克族食管癌的关系,分析影响哈萨克族食管癌患者预后的因素,旨在为新疆哈萨克族食管癌防治提供依据。方法:收集2010-2015年间新疆哈萨克族食管癌患者192例,非食管癌对照200例,离子捕捉免疫分析法(Ion capture immunoassay,ICIA)测定血清叶酸水平,甲基化特异性聚合酶链反应(methylation specific PCR,MSP)技术检测其外周血中MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因启动子区甲基化水平,Log-rank检验和Cox比例风险回归模型(Cox’s proportional hazards regression model,简称Cox模型)分析哈萨克族食管癌预后因素。结果:1.病例组血清叶酸水平低于对照组(Z=—9.13,P=0.000),差异有统计学意义;2.基因甲基化水平分析:病例组MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因的甲基化率均高于对照组,差异均有统计学意义(χ~2=45.144,P=0.000;χ~2=18.465,P=0.000;χ~2=11.853,P=0.003;χ~2=37.359,P=0.000;χ~2=46.608,P=0.000;χ~2=14.766,P=0.001);3.基因甲基化与临床病理特征的关系:MTHFR基因甲基化与食管癌的性别、年龄和病理分型(χ~2=4.099,P=0.043;χ~2=12.800,P=0.005;χ~2=9.851,P=0.0 2 0)、C B S基因甲基化与食管癌的病理分型、浸润程度和T N M分期(χ~2=24.463,P=0.000;χ~2=4.488,P=0.034;χ~2=6.412,P=0.041)、MGMT基因甲基化与食管癌的肿瘤大小、分化程度、区域淋巴结转移和TNM分期(χ~2=5.424,P=0.020;χ~2=7.412,P=0.006;χ~2=6.692,P=0.010;χ~2=10.739,P=0.005)、P16基因甲基化与食管癌的分化程度、浸润程度和TNM分期(χ~2=6.356,P=0.012;χ~2=10.478,P=0.001;χ~2=11.646,P=0.003)、FHIT基因甲基化与食管癌的病理分型和TNM分期(χ~2=15.479,P=0.001;χ~2=12.564,P=0.002)、RASSF1A基因甲基化与食管癌的分化程度、区域淋巴结转移和TNM分期(χ~2=4.123,P=0.042;χ~2=14.884,P=0.000;χ~2=6.709,P=0.035),差异均有统计学意义。4.多因素Cox回归分析显示:肿瘤浸润程度(χ~2=7.961,P=0.005)、区域淋巴结转移(χ~2=16.135,P=0.000)、TNM分期(χ~2=4.789,P=0.029;χ~2=7.509,P=0.006)、CBS基因甲基化(χ~2=6.212,P=0.013)和RASSF1A基因甲基化(χ~2=6.355,P=0.012)是影响食管癌预后的独立危险因素,女性性别(χ~2=4.981,P=0.026)和血清叶酸(χ~2=8.794,P=0.003;χ~2=8.165,P=0.004;χ~2=5.130,P=0.024)是食管癌预后的保护因素。结论:MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因甲基化均与新疆哈萨克族食管癌的发生密切相关,肿瘤浸润程度、区域淋巴结转移、TNM分期、CBS和RASSF1A基因甲基化是影响食管癌预后的独立危险因素,女性性别和血清叶酸是保护因素。