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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 Thr399Ile  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 Thr399Ile  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 Thr399Ile ). 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 Thr399Ile  [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.

bmc cancer

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