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 (JAM-A) 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 (χ 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.

Effects of JAM-A rs790056 and LFA-1 rs8058823 Variations on Kidney Cancer

“…The frequencies of the major TT genotype and allele were not found to be statistically different in breast cancer. Furthermore, the heterozygote TC genotype and minor CC genotype were also found similar in patients with breast cancer and control groups (p>0.05) (14). In our study, we did not observe any differences between the study group for the frequencies of genotypes and alleles.…”

“…They suggested that the A allele may be associated with the risk of breast cancer by affecting leukocyte diapedesis. Opposite to the results by Tokat et al (14), Fu et al (15) found that the frequencies of the AA genotype and A allele were lower in sporadic infiltrative duct breast cancer (p<0.0001). Moreover, the heterozygote AG genotype was observed to be higher (p<0.0001).…”

“…The frequency of the AA genotype of LFA-1 rs8058823 was found to be higher, while for the AG genotype, it was found to be lower in CHD, and the major AA genotype was identified as the risk factor for CHD (10). Tokat et al (14) showed that the frequencies of the AA genotype and A allele were statistically higher in patients with breast cancer (p<0.05). They suggested that the A allele may be associated with the risk of breast cancer by affecting leukocyte diapedesis.…”

Investigation of JAM-A (rs790056) and LFA-1 (rs8058823) gene variants in Turkish colorectal cancer patients

“…Tokat et al ( 16) identified the TT genotype and T allele of JAM-A rs790056 as risk factors for coronary heart disease. JAM-A rs790056T was found to be higher in the breast cancer group than in the control group (13). On the other hand, T allele was found to be higher in the control group than in the patient group (50% and 62.68%, respectively).…”