title: Genetic variation in MUC1, MUC2 and MUC6 genes and evolution of gastric cancer precursor lesions in a long-term follow-up in a high-risk area in Spain.
abstract: In order to assess whether inherited genetic variability in the mucin genes associates with the evolution of gastric cancer precursor lesions (GCPLs), we genotyped 22 tagSNPs in MUC1, MUC6 and MUC2 genes of 387 patients with GCPLs that had been followed up for 12.8 years. According to the diagnosis at recruitment and at the end of follow-up, the lesions did not change in 43.1% of the patients, regressed in 28.7% and progressed in 28.2%. Three SNPs in the 3'-moiety of MUC2 were significantly associated with a decreased risk of progression of the lesions, whereas another four SNPs, located at the 5'-moiety, were found to be significantly associated either with increased [one single-nucleotide polymorphism (SNP)] or decreased (three SNPs) probability of regression. Stratified analysis indicated that significance was maintained only in those subjects positive for Helicobacter pylori infection and in those not consuming non-steroidal anti-inflammatory drugs, which were found protective against lesion progression. Haplotype analyses indicated the presence of two haplotypes, one in each moiety of the gene, that were significantly associated with decreased risk of progression of the lesions [odds ratio (OR) = 0.49 and 0.46; 95% confidence interval (CI) = 0.28-0.85 and 0.25-0.86, respectively]. The 5'-end haplotype was also associated with increased probability of regression (OR = 1.67; 95% CI = 1.02-2.73), altogether suggesting a protective role against progression of the precancerous lesions. No significant association was found with variants in MUC1 and MUC6 genes. These results indicate, for the first time, that genetic variability in MUC2 is associated with evolution of GCPLs, especially in H.pylori infected patients, suggesting a role of this secreted mucin in gastric carcinogenesis.
authors.affiliation: Translational Research Laboratory, Institut Català d'Oncologia (IDIBELL-ICO), Gran Via, km 2.7 s/n, 08907 L'Hospitalet de Llobregat, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Marín
authors.forename: Catalina
authors.initials: C
authors.lastname: Bonet
authors.forename: Xavier
authors.initials: X
authors.lastname: Muñoz
authors.forename: Nadia
authors.initials: N
authors.lastname: García
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Pardo
authors.forename: Juan Maria
authors.initials: JM
authors.lastname: Ruiz-Liso
authors.forename: Pablo
authors.initials: P
authors.lastname: Alonso
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellà
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Sanz-Anquela
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D013030:Spain; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009077:Mucins