RESUMO
Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Incidência , Peptídeos/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Medição de Risco/métodos , Sensibilidade e Especificidade , Neoplasias Gástricas/epidemiologia , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: The trefoil factor 1 protein (pS2/TFF1) is a candidate tumor-suppressor protein, and it is a pleiotropic factor involved in the organization and homeostasis of the gastrointestinal tract and various inflammatory or neoplastic diseases. The purpose of this study was to assess the expression of pS2/TFF1 and its clinicopathologic relationship, including the p53 and Ki-67 labeling index, in colorectal carcinogenesis. METHODS: The expression of pS2/TFF1 protein was evaluated immunohistochemically in 45 samples of normal colonic mucosa, 43 samples of adenoma and 186 samples of colorectal carcinoma. RESULTS: pS2/TFF1 protein was expressed weakly in 37.8% of normal colonic mucosa samples, and it had a weak to strong expression in 48.8% of adenomas and 28% of colorectal adenocarcinomas. pS2/TFF1 expression in carcinoma was slightly increased in the poorly differentiated group compared with the well to moderately differentiated group (p=0.059). Interestingly, mucinous carcinoma (4/4) and signet ring cell carcinoma (2/3) showed significant increase of pS2/TFF1 expression. pS2/TFF1 expression was inversely correlated with the p53 protein expression and the Ki-67 labelling index (p<0.05). There was no significant correlation with the tumor size, metastasis or pathologic staging. CONCLUSIONS: Overexpression of pS2/TFF1 expression in colorectal adenocarcinoma was inversely correlated with the Ki-67 labelling index and the p53 expression in cancer. These results suggest that pS2/TFF1 protein may contribute as tumor suppressor factor in colorectal adenocarcinoma.