Interactive Effects of Common Haplotypes of Two Leukocyte Diapedesis-Related Genes, LFA-1 and JAM-A on Breast Cancer Risk

Abstract

Leukocyte diapedesis is an important process in breast cancer etiopathogenesis. Therefore, Junctional adhesion molecule-A (JAMA) and lymphocyte function-associated antigen-1 (LFA-1) genes are among potential candidate genes involved in breast cancer development. In the present study, JAM-A rs790056 (T > C), LFA-1 rs8058823 (A > G) and LFA-1 rs2230433 (C > G) gene variations and their associations with breast cancer risk were investigated in breast cancer patients and healthy subjects. The JAM-A and LFA-1 genotypes were determined in 108 breast cancer patients and 63 healthy controls with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. LFA-1 rs8058823 common AA genotype (x(2) = 6.062, p = 0.014) and A allele frequency (p = 0.001) and LFA-1 rs2230433 rare GG genotype frequency (p = 0.048) was higher in the patient group compared with controls. The TA haplotype (JAM-A rs790056-T, LFA-1 rs8058823-A alleles) frequency was significantly increased in the patient group compared with controls (p = 0.0173), while the TG haplotype (JAM-A rs790056-T, LFA-1 rs8058823-G alleles) and CG haplotype (LFA-1 rs2230433-C, LFA-1 rs8058823-G alleles) frequencies were significantly lower in the patient group compared with controls (p = 0.0051 and p = 0.002, respectively). In addition, the TCG haplotype (JAM-A rs790056-T, LFA-1 rs2230433-C, LFA-1 rs8058823-G alleles) frequency was significantly lower in the patient group compared with controls (p = 0.0096). Haplotype analysis confirmed that the LFA-1 rs8058823 is more effective in breast cancer risk than LFA-1 rs2230433 and JAM-A rs790056. LFA-1 rs8058823 A allele may be related to breast cancer risk, influencing leukocyte diapedesis. Our findings indicate that functional gene variations associated with leukocyte diapedesis may affect breast cancer risk.