Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, People's Republic of China.
Gene. 2013 Oct 15;529(1):104-12. doi: 10.1016/j.gene.2013.07.070. Epub 2013 Aug 7.
The polymorphisms in trefoil factor (TFF) gene family that protect gastrointestinal epithelium might influence individual vulnerability to gastric cancer (GC) and atrophic gastritis. We used the Sequenom MassARRAY platform to identify the genotypes of TFF2 rs3814896 and TFF3 rs9981660 polymorphisms in 478 GC patients, 652 atrophic gastritis patients, and 724 controls. For the TFF2 rs3814896 polymorphism, in the subgroup aged ≤ 50 years, we found that AG+GG genotypes were associated with a 0.746-fold decreased risk of atrophic gastritis [p=0.023, 95% confidence interval (CI)=0.580-0.960], a 0.626-fold decreased risk of GC (p=0.005, 95% CI=0.451-0.868), and a 0.663-fold decreased risk of diffuse-type GC (p=0.034, 95% CI=0.452-0.970) compared with the common AA genotype. For the TFF3 rs9981660 polymorphism, in the male subgroup, individuals with variant AG+AA genotype were associated with a 0.761-fold decreased risk of diffuse-type GC compared with the common GG genotype (p=0.043, 95% CI=0.584-0.992). Additionally, we found that in subjects aged ≤ 50 years compared with common AA genotype, TFF2 rs3814896 AG+GG genotypes were associated with increased TFF2 mRNA levels in the total gastric cancer specimens and in the diffuse-type gastric cancer specimens; and in males aged ≤ 50 years compared with common GG genotype, TFF3 rs9981660 AA+AG genotypes were associated with TFF3 mRNA levels in diffuse-type gastric cancer tissues and their corresponding non-cancerous tissues. To our knowledge, this is the first report of an association between the TFF2 rs3814896 AG+GG genotypes and decreased risks of GC, diffuse-type GC, and atrophic gastritis in younger people aged ≤ 50 years, and an association between TFF3 rs9981660 AG+AA genotype and decreased risk of diffuse-type GC in men. Moreover, we found that TFF2 rs3814896 AG+GG genotypes in people aged ≤ 50 years and TFF3 rs9981660 AG+AA genotypes in younger males with diffuse-type GC were associated with higher levels of TFF2 and TFF3 mRNA respectively.
三叶因子（TFF）基因家族的多态性可保护胃肠道上皮，可能影响个体患胃癌（GC）和萎缩性胃炎的易感性。我们使用Sequenom MassARRAY 平台鉴定了 478 例 GC 患者、652 例萎缩性胃炎患者和 724 例对照中 TFF2 rs3814896 和 TFF3 rs9981660 多态性的基因型。对于 TFF2 rs3814896 多态性，在≤50 岁的亚组中，我们发现 AG+GG 基因型与萎缩性胃炎的风险降低 0.746 倍相关 [p=0.023，95%置信区间（CI）=0.580-0.960]、GC 的风险降低 0.626 倍（p=0.005，95% CI=0.451-0.868）和弥漫型 GC 的风险降低 0.663 倍（p=0.034，95% CI=0.452-0.970）与常见 AA 基因型相比。对于 TFF3 rs9981660 多态性，在男性亚组中，与常见 GG 基因型相比，变异 AG+AA 基因型个体与弥漫型 GC 的风险降低 0.761 倍相关（p=0.043，95% CI=0.584-0.992）。此外，我们发现，与常见 AA 基因型相比，在≤50 岁的患者中，TFF2 rs3814896 AG+GG 基因型与总胃癌标本和弥漫型胃癌标本中 TFF2 mRNA 水平升高相关；在≤50 岁的男性中，与常见 GG 基因型相比，TFF3 rs9981660 AA+AG 基因型与弥漫型胃癌组织及其相应的非癌组织中 TFF3 mRNA 水平相关。据我们所知，这是首次报道 TFF2 rs3814896 AG+GG 基因型与≤50 岁年轻人 GC、弥漫型 GC 和萎缩性胃炎风险降低相关，以及 TFF3 rs9981660 AG+AA 基因型与男性弥漫型 GC 风险降低相关的报告。此外，我们发现，在≤50 岁的人群中，TFF2 rs3814896 AG+GG 基因型和在患有弥漫型 GC 的年轻男性中 TFF3 rs9981660 AG+AA 基因型分别与 TFF2 和 TFF3 mRNA 水平升高相关。
