Genetic variation analysis in a follow-up study of gastric cancer precursor lesions confirms the association ofMUC2variants with the evolution of the lesions and identifies a significant association withNFKB1andCD14
| Autor: | Javier P. Gisbert, Carlos González, Sergio Lario, Nadia García, Angel Cosme, Luis Ortega, Catalina Bonet, Beatriz Madrigal, Mª Magdalena Adrados, Laura Espinosa, Luis Bujanda, María José Ramírez-Lázaro, Victoria Andreu, José Miguel Sanz-Anquela, J.L. Mendoza, María Berdasco, Guillermo Muñoz, Elvira Poves, Angel Ferrandez, Osmel Companioni, Miriam Cuatrecasas, Núria Sala, José Juan Pozo-Kreilinger, Jesús Barrio, Xavier Calvet, Ma José Paúles, Ignasi Elizalde |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Oncology Cancer Research Candidate gene medicine.medical_specialty Genotype Lipopolysaccharide Receptors Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Helicobacter Infections 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Internal medicine Genetic variation medicine Humans Genetic Predisposition to Disease Longitudinal Studies Genetic variability Stomach cancer Aged Genetic association Mucin-2 Helicobacter pylori NF-kappa B p50 Subunit Cancer Middle Aged medicine.disease Genetic marker 030220 oncology & carcinogenesis Disease Progression 030211 gastroenterology & hepatology Precancerous Conditions Follow-Up Studies |
| Zdroj: | Zaguán. Repositorio Digital de la Universidad de Zaragoza instname |
| ISSN: | 0020-7136 |
| Popis: | Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow-up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis. |
| Databáze: | OpenAIRE |
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