ABSTRACT
BACKGROUND/AIMS: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. METHODS: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. RESULTS: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 high-grade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). CONCLUSIONS: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Basic Helix-Loop-Helix Transcription Factors/genetics , DNA Methylation , Gastrectomy/methods , Genes, APC/physiology , Genes, mos/genetics , Incidence , Multivariate Analysis , Neoplasms, Second Primary/epidemiology , Proportional Hazards Models , Risk Factors , Stomach Neoplasms/genetics , Thrombomodulin/geneticsABSTRACT
Background: Among colorectal cancer hereditary variants, two syndromes show a predisposition to the disease based on germline mutations: Familial Adenomatous Polyposis (FAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Aim: To screen mutations in FAP and HNPCC families in Chile. Materials and Methods: Two FAP and one HNPCC families were studied. The APC gene (for FAP patients) and the MLH1 gene (for HNPCC patients), were screened for mutations on genomic DNA. The molecular analysis was performed through polymerase chain reaction, Single Strand Conformer Polymorphism (SSCP) and DNA sequencing. Mutations were defined as changes in the DNA sequence leading into a stop codon and a truncated protein. Results: In the two FAP families the analysis revealed a mutation consisting in the deletion of five nucleotides named c.3927_3931delAAAGA. The genetic study of the HNPCC family demonstrated the insertion of one adenine in codon 168 of exon 6, named c.504insA. Discussion: Germ-line mutations were identified in the three families. The relevance of these studies in a better knowledge of cancer susceptibility, and the possibility of identifying in relatives in risk by molecular diagnosis.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Adenomatous Polyposis Coli/genetics , Colorectal Neoplasms/genetics , Genes, APC/physiology , Mutation/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms/diagnosis , Gene Frequency , Germ-Line Mutation/genetics , Pedigree , Sequence Analysis, DNAABSTRACT
Colorectal cancer CRC is one of the most common malignancies worldwide. Advances in molecular techniques have provided deep insight into the molecular pathogenesis, biologic and genetic changes occurring in colon cancer patients. Current theories of malignant transformation postulate that development of colon cancer is related to 2 main pathways; the loss of heterozygosity pathway, which is usually due to a defect in the adenomatous polyposis coli APC gene and microsatellite instability, which is usually due to a defect in mismatch repair MMR genes. This review summarizes the role of the wingless signaling pathway genes including APC and MMR genes in the development of CRC
Subject(s)
Humans , Genes, APC/physiology , DNA Repair/genetics , Signal Transduction/genetics , Loss of Heterozygosity/genetics , Microsatellite RepeatsABSTRACT
O câncer colorretal ainda é uma das neoplasias de maior importância no mundo ocidental. O grande desenvolvimento da genética e biologia molecular nos últimos anos permitiu um melhor conhecimento dos mecanismos biomoleculares no câncer, e em especial, no câncer colorretal. Oncogenes (K-ras), genes supressores de tumor (p53, DCC e APC) e genes reparadores de DNA (hMSH2, MLH1, PMS1 e 2) estäo envolvidos na progressäo da seqüência adenoma-carcinoma no cólon e no reto. Algumas características anatômicas, histopatológicas, epidemiológicas e o comportamento biológico dos tumores parecem estar relacionados com alteraçöes genéticas específicas nestes genes. O conhecimento dos mecanismos genéticos que promovem a carcinogênese dos tumores colorretais abre novas perspectivas para o diagnóstico, tratamento, prognóstico e seguimento dos pacientes acometidos por esta neoplasia