晚期糖基化终末产物受体2184A/G基因多态性与肺癌的相关性研究

Association between receptor for advanced glycation end-products 2184A/G gene polymorphism and lung cancer

目的探讨晚期糖基化终产物受体(RAGE)2184A/G基因的多态性与肺癌发生发展的关系。方法选取年龄、性别匹配的275例肺癌患者和126名健康者,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测RAGE 2184A/G基因多态性的分布频率。结果 2148A/G多态性的分析中,健康者中仅发现野生型A等位基因,基因频率为100.0%。3种不同类型肺癌均显示最小等位基因G条带,其中腺癌患者G等位基因频率为7.0%,鳞癌为6.1%,小细胞癌为7.7%(均P<0.05),未能检测出纯合的GG。在不同分期的肺癌患者中,腺癌患者AG基因型频率为14.0%,早中期患者AG基因型频率为3.2%,晚期肺癌AG基因型频率明显升高,为20.4%(P=0.048)。鳞癌患者AG基因型频率为12.2%,早中期鳞癌患者AG基因型频率为8.0%,而晚期鳞癌患者AG基因型频率可高达16.7%(P=0.05)。小细胞癌患者AG基因型频率为15.4%。在腺癌和鳞癌患者中,男性AA基因型频率明显低于女性,分别为81.4%和90.7%以及81.3%和100.0%;而在小细胞癌患者中,男性AA基因型频率(100.0%)明显高于女性患者(50.0%)。结论 RAGE 2148A/G基因多态性与肺癌的发生密切相关。在肺癌和腺癌中,AG基因型频率与肺癌的恶性程度呈正相关,同时肺癌患者2184A/G多态性具有显著的性别差异。RAGE 2148A/G基因有望成为肺癌基因治疗的靶向之一。

Objective To investigate the association between receptor for advanced glycation endproducts（ RAGE） 2184 A/G gene polymorphism and lung cancer. Methods Using the method of PCR-restriction fragment length polymorphism（ PCR-RFLP）,the 2184 A/G genotype of RAGE were examined in275 lung cancer patients and 126 control subjects whose age and sex were matched. The associations of the RAGE 2184 A/G gene polymorphisms and development of lung cancer were analysed. Results In healthy control population,we only recognized wild type A allele（ 100. 0%）,all three type of lung cancer revealed appearance of minor G allele. In adenocarcinoma patients,the frequency of G allele was 7. 0%,squamous cell carcinoma was 6. 1%,and small cell carcinoma was 7. 7%. There was statistical significant difference between cancer group and healthy control group（ P〈0. 05）. We didn＇t not detect pure GG. In different stages of lung cancer patients,the genotype frequency of AG in adenocarcinoma patients was 14. 0%,while in early/middle stage was 3. 2%,and in late stage was increased significantly to 20. 4%（ P = 0. 048）. The genotype frequency of AG in squamous cell carcinoma patients was 12. 2%,while in early/middle stage was8. 0%,and in late stage was increased significantly to 16. 7%（ P = 0. 05）. AG genotype frequency was15. 4% in small cell carcinoma patients,the genotype frequency of AA in male patients with adenocarcinoma and squamous cell carcinoma was significantly lower than that of female（ 81. 4% vs 90. 7%; 81. 3% vs100. 0%）. In small cell carcinoma,the AA genotype frequency was significantly higher in male patients（ 100. 0%） than in female patients（ 50. 0%）. Conclusions RAGE 2148A/G gene polymorphism is closely related to the occurrence of lung cancer. The frequency of AG genotype in lung cancer and adenocarcinoma was positively correlated with the degree of malignancy of lung cancer. 2184 A/G polymorphism in patients with lung cancer has significant gender differences. RAGE 2148 A/G gene is expected to be one of the target of gene therapy for lung cancer.