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Reduced or null expression of E-cadherin protein is a frequent cause of diffuse gastric cancer (DGC). More than 50% of patients with DGC present somatic variants in CDH1 gene. The objectives of this study were to study E-cadherin expression and identify variants in the CDH1 gene in gastric tumors of patients with DGC. We studied 18 Mexican DGC patients who attended a hospital of the Mexican Social Security Institute; E-cadherin expression was determined by immunohistochemistry, and variants were identified by Sanger sequencing in promoter and coding regions. Predictive analysis was performed using PolyPhen-2 and HOPE software. We found that 56% of DGC patients showed reduced expression of E-cadherin. All patients carried CDH1 variants; overall, 12 different CDH1 variants were identified. Predictive analysis revealed that the rs114265540 variant was probably damaging, with a value of 0.985, indicating a functional impact on the E-cadherin protein. Variants rs34939176 and rs33964119 were identified as risk factors for DGC (odds' ratios [OR] = 31.3, 95% CI 6.3-154.0, p < 0.001; OR = 6.1, 95% CI 2.0-19.0, p < 0.001, respectively) given their elevated frequency and by comparing it with those reported for MXL population in the 1000 Genomes Project database. In this Mexican population, the percentage of diffuse gastric tumors with reduced expression of E-cadherin was similar to that reported in other populations. All gastric tumors of DGC patients studied had somatic CDH1 gene variants; however, the rs114265540, rs34939176, and rs33964119 variants were importantly related to DGC.


Azaria García-Ruvalcaba, Katia C Vázquez-Ibarra, María T Magaña-Torres, Lourdes Del C Rizo de-la-Torre, Lennon Meléndez-Aranda, Gabriela López-Armas, José A Cruz-Ramos, Jorge Peregrina-Sandoval, Esther Espinoza-Jiménez, María E Rosales-Gradilla, Josefina Y Sánchez-López. Low expression of E-Cadherin and CDH1 variants associated with diffuse gastric cancer. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2023 Feb 20;75(1):037-044

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PMID: 36652613

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