CTLA-4基因启动子区-1661和-318位点多态性与胃癌的关系

细胞毒性T淋巴细胞相关抗原4（CTLA-4）是一种免疫调节分子，可通过降低T细胞活性，抑制机体的抗肿瘤免疫反应。目的：探讨CTLA-4基因启动子区-1661和-318位点多态性与胃癌的关系。方法：121例无血缘关系的胃癌患者和236名正常对照者纳入研究，分别采用聚合酶链反应一限制性片段长度多态性（PCR—RFLP）和扩增不应突变系统（ARMS）。PCR检测CTLA-4基因启动子区-1661和．318位点多态性。结果：胃癌组．1661位点AA基因型和A等位基因频率显著低于正常对照组（73．6％对83．9％，P=0．024；85．1％对91．1％，P=0．022）；而-318位点CC基因型和C等位基因频率与正常对照组相比无明显差异。管状腺癌患者CTLA-4基因启动子区-1661位点AA基因型和．318位点CC基因型频率显著低于正常对照组（64．1％对83．9％，P=0．001；76．6％对87．3％，P=0．047）。结论：CTLA-4基因启动子区-1661位点基因多态性与胃癌呈显著负相关，-1661和-318位点多态性与管状腺癌呈显著负相关。

Association between CTLA-4 Gene Promoter Region Polymorphisms at Positions-1661 and-318 and Gastric Cancer

Background： Cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） is a potent immunoregulatory molecule that suppresses antitumor immunoreaction by down-regulating T-cell activation. Aims： To investigate the association between CTLA-4 gene promoter region polymorphisms at positions -1661 and -318 and gastric cancer. Methods： Unrelated 121 gastric cancer patients and 236 healthy controls were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and amplification refractory mutation system （ARMS）-PCR were used to assess CTLA-4 gene promoter region polymorphisms at positions -1661 and -318, respectively. Results： The frequencies of AA genotype and A allele at position -1661 were statistically lower in gastric cancer patients than in healthy controls （73.6% vs. 83.9%, P=0.024; 85.1% vs. 91.1%, P=0.022）. The frequencies of CC genotype and C allele at position -318 were not significantly different between gastric cancer patients and healthy controls. Both the frequencies of AA genotype at position -1661 and CC genotype at position -318 were statistically lower in tubular adenocarcinoma patients than in healthy controls （64.1% vs. 83.9%, P=0.001; 76.6% vs. 87.3%, P=0.047）. Conclusions： CTLA-4 gene promoter region polymorphism at position -1661 shows a significantly negative association with gastric cancer, while those at positions -1661 and -318 show a significantly negative association with tubular adenocareinoma.