[Role of polymorphism of certain cytokines in gastric cancer in Mexico. Preliminary results].
BACKGROUND
Interleukin-10, tumor necrosis factor alpha, Interleukin-1 beta and interleukin-1 receptor antagonist cytokines modulate the inflammatory response in presence of Helicobacter pylori. Pro-inflammatory interleukin 10 (IL-10-592, -1082), TNF alpha (TNF alpha-308), interleukin-1 beta and interleukin-1 receptor antagonist (IL-1B-31*C and IL-1RN*2/*2) genotypes have been associated with higher risk of gastric cancer in Caucasians. The aim of this study was to investigate whether these same genotypes are involved in susceptibility to gastric cancer in Mexican population.


METHODS
DNA from 33 unrelated Mexican patients with histologically confirmed gastric cancer (n = 25) or high-grade dysplasia (n = 8) (mean age 62.7, F/M = 0.37) and 25 ethnically matched healthy controls (mean age = 39.9, F/M = 3.12) were studied. All cases and controls had evidence of H. pylori infection as shown by at least two positive results from the following diagnostic tests: rapid urease test; culture; histology, or detection of IgG anti-H. pylori antibodies. The -592, -1082 polymorphism in IL-10 gene, the -308 in TNF alpha gene, and the-31 polymorphism in the IL-1B gene were typed by 5' nuclease PCR assays (TaqMan) and the variable number of tandem repeats polymorphism in intron 2 of the 1L-1RN gene was typed by PCR and amplicon sizing as previously described (Nature 2000; 404: 398).


RESULTS
Carriage of the pro-inflammatory IL-1B-31*C allele was associated with increased risk of gastric cancer or high-grade dysplasia (OR: 8.7, 95% confidence interval [CI] = 1.5-66.9). No association was found between any IL-IRN, IL-10 or TNF alpha genotypes and gastric cancer or high-grade dysplasia. Logistic regression analysis identified male gender and carriage of IL-1B-31*C as independent risk factors for gastric cancer (OR = 9.2, 95% CI = 2.4-34.5, and OR = 10, 95% CI = 1.6-64, respectively).


CONCLUSIONS
The results of this preliminary study confirm that the pro-inflammatory IL-1B genotypes, as well as male gender, are risk factors for development of gastric cancer in Mexican population.
Garza-González
Elvira
E
Departamento de Microbiología, Facultad de Medicina, U.A.N.L., México.
Hold
Georgina
G
Pérez-Pérez
Guillermo Ignacio
GI
Bosques-Padilla
Francisco Javier
FJ
Tijerina-Menchaca
Rolando
R
Maldonado-Garza
Héctor Jesús
HJ
el-Omar
Emad
E
D000328:Adult; D000368:Aged; D000483:Alleles; D000907:Antibodies, Bacterial / Q000032:analysis; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005838:Genotype; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000276:immunology
D000907:Antibodies, Bacterial; D016207:Cytokines; D007375:Interleukin-1