School of Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran.
Gene. 2012 Jan 15;492(1):100-3. doi: 10.1016/j.gene.2011.10.048. Epub 2011 Nov 7.
TFF1 is a cysteine-rich protein that forms a characteristic trefoil domain through disulfide bonds, which render it resistant to vigorous conditions and it involves in maintaining the integrity of the gastric mucosa. Decreased expression of TFF1 gene plays a role in the development of gastric cancer. We examined the association between the promoter polymorphisms of the TFF1 gene and the risk of development of gastric cancer, in a case-control study including 199 controls and 141 patients with gastric cancer. Assessment of single nucleotide polymorphisms in the promoter region of the TFF1 gene was performed by sequencing and polymerase chain reaction-based restriction fragment length polymorphism. We found a statistically significant increased risk of gastric cancer associated with -394 TT genotypes (OR=8.78, CI=2.85-27.05, p<0.001) and CT (OR=1.64, CI=1.04-2.60, p=0.033). This single nucleotide polymorphism occurs naturally in an estrogen response element. According to induction of the TFF1 gene by estrogen, it is possible that the substitution of C to T results in a decreased estrogen receptor binding affinity to the estrogen response element and in turn it decreases the expression of the TFF1 gene that may be involved in development of gastric cancer over a lifetime.
TFF1 是一种富含半胱氨酸的蛋白质，通过二硫键形成特征性三叶因子结构域，使其能够耐受剧烈条件，并参与维持胃黏膜的完整性。TFF1 基因表达下调在胃癌的发展中起作用。我们在包括 199 名对照和 141 名胃癌患者的病例对照研究中，研究了 TFF1 基因启动子多态性与胃癌发展风险之间的关联。通过测序和聚合酶链反应-基于限制片段长度多态性的方法评估 TFF1 基因启动子区域的单核苷酸多态性。我们发现 -394 TT 基因型与胃癌的发病风险呈统计学显著相关（OR=8.78，95%CI=2.85-27.05，p<0.001）和 CT（OR=1.64，95%CI=1.04-2.60，p=0.033）。这个单核苷酸多态性自然发生在雌激素反应元件中。根据雌激素对 TFF1 基因的诱导作用，C 到 T 的取代可能导致雌激素受体与雌激素反应元件的结合亲和力降低，从而降低 TFF1 基因的表达，这可能涉及一生中胃癌的发生。
