Intercellular adhesion molecule-1 genetic markers (+241G/A and +469A/G) in Iranian women with breast cancer

Abstract

Breast cancer is the most common cancer among women, the second-most leading cause of women's death after lung cancer. ICAM-1 is a cell adhesion molecule that belongs to the Ig-superfamily, with a glycoprotein structure playing a key role in leukocyte recruitment into inflammatory sites, as well as in leukocyte activation and effector function. Proteolytic cleavage of ICAM-1 results in the formation of a soluble form, sICAM-1, which is present in low-serum levels in healthy individuals but becomes elevated in inflammatory and malignant conditions. The ICAM1 gene is located on chromosome 19 and contains two well-known single-nucleotide polymorphisms (SNP) of +241G/A (G241R) and +469A/G (K469E). In this study, the frequencies of the two polymorphisms were investigated in breast cancer patients and healthy individuals. For G241R, we selected 276 breast cancer patients and 235 healthy sex-matched controls, and for K469E, 264 patients and 200 healthy sex-matched controls were chosen. The results of this study show that the frequency of the GA genotype was significantly higher in breast cancer patients in comparison to the control group ( P = 0.007). In addition, the frequency of the R allele was significantly higher in breast cancer patients compared to controls ( P = 0.008). However, both the genotype and allele frequency of K469E did not differ significantly between patients and controls. A significant difference was observed in the frequency of genotype combination A/G (+241 G/A and +469 A/G, respectively) between patients and controls (6.2 vs. 2.2%; ∗ P = 0.007). These findings indicate that individuals carrying the A allele of the ICAM1 gene as well as the A/G haplotype may have a higher risk of developing breast cancer.