Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8-251 polymorphisms in the risk for the development of distal gastric cancer

Background: The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC). The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses. Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399lle and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population. Methods: We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399lle by PCR- RFLP and for IL8-251 by the amplification refractory mutation system (ARMS)-PCR. Results: The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square(H-W) = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399lle). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for TLR4-Asp299Gly [the 7.7% of distal GC patients and 7.7% non- cancer controls (p = 0.82)] and for TLR4 Thr399lle [the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1-4.2) (p = 0.023). Conclusion: This study showed that the IL8-251* A allele could be related to the development of distal gastric cancer in this Mexican population.