International Journal of Hematology and Oncology
2024, Vol 34, Num 4 Page(s): 045-052
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Interactive Effects of Common Haplotypes of Two Leukocyte Diapedesis-Related Genes, LFA-1 and JAM-A on Breast Cancer Risk
Bengu TOKAT1, Tulin OZTURK2, M. Fatih SEYHAN1, Zerrin CALAY2, Sennur ILVAN2, Mete B. TUZUNER1, Oguz OZTURK1, Hulya YILMAZ-AYDOGAN1
1Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Molecular Medicine, Istanbul, TURKEY
2Istanbul University, Cerrahpasa Medical School, Department of Pathology, Istanbul, TURKEY
Keywords: Breast cancer, Gene, Junctional adhesion molecule-A, Lymphocyte function-associated antigen-1, Haplotype
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 (χ2= 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.
Bengu TOKAT1, Tulin OZTURK2, M. Fatih SEYHAN1, Zerrin CALAY2, Sennur ILVAN2, Mete B. TUZUNER1, Oguz OZTURK1, Hulya YILMAZ-AYDOGAN1
1Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Molecular Medicine, Istanbul, TURKEY
2Istanbul University, Cerrahpasa Medical School, Department of Pathology, Istanbul, TURKEY
Keywords: Breast cancer, Gene, Junctional adhesion molecule-A, Lymphocyte function-associated antigen-1, Haplotype
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 (χ2= 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.
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