Polymorphisms in TNF and HSP-70 show a significant association with gastric cancer and duodenal ulcer.
Tumour Necrosis Factor (TNF) and Heat Shock Protein 70 (HSP70) are important molecules in inflammatory, infectious and tumoral processes. The genes codifying these molecules are polymorphic and certain alleles have been associated with susceptibility to disease. Gastric cancer is associated with an Helicobacter pylori-induced chronic inflammatory response. The aim of this work was to analyze whether polymorphisms in inflammation-related genes are associated with the development of gastric cancer. We studied 447 Mexican adult patients including 228 with non-atrophic gastritis, 98 with intestinal metaplasia, 63 with gastric cancer and 58 with duodenal ulcer, and 132 asymptomatic individuals as well. DNA from peripheral white blood cells was typed for the Single Nucleotide Polymorphisms (SNPs) -308 of TNF-alpha, +252 of TNF-beta, +190 of HSP70-1, +1267 of HSP70-2 and +2437 of HSP70-HOM. Compared with the asymptomatic group, we found a significant association of TNF-beta*A and HSP70-1*C alleles with gastric cancer (OR 5.69 and 3.76, respectively) and HSP70-1*C with duodenal ulcer (OR 3.08). Genotype TNF-beta G/G showed a significant gene-dose effect with gastric cancer (OR 0.09); whereas HSP70-1 C/G showed significant association with both, gastric cancer (OR 13.31) and duodenal ulcer (OR 16.19). Polymorphisms in TNF and HSP70 showed a significant severity-dose-response as risk markers from preneoplastic lesions to gastric cancer in Mexican population, probably because of their association with an intense and sustained inflammatory response.
Partida-Rodríguez
Oswaldo
O
Immunology Research Unity, Pediatric Hospital, CMN S-XXI, IMSS, Mexico City CP 06720, Mexico.
Torres
Javier
J
Infectious Diseases Research Unity, Pediatric Hospital, CMN S-XXI, IMSS, Mexico City CP 06720, Mexico.
Flores-Luna
Lourdes
L
Instituto Nacional de Salud Pública, Cuernavaca, Morelos CP 62100, Mexico.
Camorlinga
Margarita
M
Infectious Diseases Research Unity, Pediatric Hospital, CMN S-XXI, IMSS, Mexico City CP 06720, Mexico.
Nieves-Ramírez
Miriam
M
Immunology Research Unity, Pediatric Hospital, CMN S-XXI, IMSS, Mexico City CP 06720, Mexico.
Lazcano
Eduardo
E
Instituto Nacional de Salud Pública, Cuernavaca, Morelos CP 62100, Mexico.
Perez-Rodríguez
Martha
M
Immunology Research Unity, Pediatric Hospital, CMN S-XXI, IMSS, Mexico City CP 06720, Mexico.
D000328:Adult; D004381:Duodenal Ulcer / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D018840:HSP70 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha