Toll-like receptor 2 -196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer.

Toll like receptors (TLR) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. The –196 to –174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2–196 to –174del polymorphism on the occurrence of non-cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non-cancer patients with abdominal discomfort and 146 healthy controls. The –196 to –174del TLR2 polymorphism was investigated using the allele-specific polymerase chain reaction method in all of the subjects. The –196 to –174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio [OR] = 6.06; 95% confidence interval [CI] = 1.86–19.72). Similarly, the frequency of the –196 to –174del/del genotype was significantly higher among NCGC patients than in non-cancer patients (adjusted OR = 2.02; 95% CI = 1.22–3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12–3.60) and diffuse-type (OR = 2.05; 95% CI = 1.11–3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the –196 to –174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population. (Cancer Sci 2007; 98: 1790–1794)