The aims of this study were to elucidate the association between RANTES-403 and an increased risk of gastric cancer in Korean males and to investigate the gene-gene interaction between IL-1B and RANTES. In total, 218 male patients with gastric cancer (114 diffuse types, 97 intestinal types, and 7 mixed types) and 377 male controls were included. RANTES-403 was genotyped, and age-adjusted odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated by logistic regression. A multifactor dimensionality reduction (MDR) test with three-way split interval validation confirmed by likelihood ratio and permutation analysis was carried out. A significant increase in the risk of gastric cancer for the intestinal-type group was observed for IL-1B-1464G carriers (OR = 2.535; 95 % CI = 1.121-5.732; P = 0.02) as well as for those with IL-1B-1464 CG (OR = 2.342; 95 % CI = 0.998-5.500; P = 0.05) or IL-1B-1464 GG (OR = 2.819; 95 % CI = 1.170-6.793; P = 0.02). For the RANTES-403 genotype, there was no significant difference in the risk of gastric cancer between the overall gastric cancer and the control groups. When further stratified according to histological types, RANTES-403A carriers (OR = 1.743; 95 % CI = 1.086-2.798; P = 0.021) or heterozygotes (OR = 1.791; 95 % CI = 1.092-2.935; P = 0.021) showed increased risk for developing diffuse-type gastric cancer. MDR revealed a three-way locus-locus interaction between RANTES-403AA, IL-1B-1464GG, and IL-1B-511CT for diffuse-type gastric cancer in Korean males. We demonstrated that RANTES-403 was significantly associated with the risk of developing diffuse-type gastric cancer in men and found a possible gene-gene interaction between RANTES and IL-1B polymorphisms in gastric cancer carcinogenesis.
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