Background: Men are more susceptible to gastric cancer (GC) than women. However, the genetic factors associated with the sex difference are not well understood. Chemokines have been shown to modulate tumor behavior, and the sex-specific effect of the chemokine polymorphisms on the host susceptibility to several diseases has been reported. We aimed to determine the role of chemokine polymorphisms on host susceptibility to GC, with special interest on their sex-specific effect.
Methods: A hospital-based case-control study, including 177 patients with GC and 217 age-matched unaffected healthy controls, was performed in three major tertiary care hospitals. Genotyping for regulated upon activation, normal T-cell expressed and secreted (RANTES) -403 A/G and -28 C/G, CC chemokine receptor 5 (CCR5) deletion, and CCR2-V64I was performed using peripheral blood DNA.
Results: The RANTES -403 GA and AA genotypes were independently associated with a 2.3-fold reduced risk of developing GC (OR=0.44, 95% CI 0.22-0.90, P=0.025) compared with GG genotype in women, but not in men. The RANTES -28C/G and CCR2-V64I polymorphisms were not associated with different risk of developing GC. The tumor stage, histological features, and survival rate were not different when stratified by RANTES -403 and -28 and CCR2-V64I genotypes.
Conclusions: Our data indicate that women who inherit A allele at RANTES -403 may be at reduced risk of GC.