Investigation of ICAM-1 and β3 Integrin Gene Variations in Patients with Brain Tumors

Abstract

Background: Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. β3 integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and β3 integrin gene polymorphisms. Materials and Methods: The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of β3 integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM-1 K469E, ICAM-1 R241G and β3 integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). Conclusions: This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.

Expression of cell adhesion molecules in laryngeal carcinoma – preliminary analysis

“…[1] showed that ICAM-1 plays an important role in tongue squamous cell carcinoma progression, which may result from the cancer cell activity, tumour angiogenic activity, lymphangiogenic activity, and increased macrophage/cancer cell adhesion. Similar results were also reported for colon carcinoma cases and in brain tumours [6, 9, 13]. The increased expression of adhesion molecules on tumour cells correlated with higher cancer progression and worse prognosis.…”

“…In many studies the relationships between ICAM-1 polymorphisms and increased incidence of carcinomas with different origin, e.g. brain and oral cavity, have been established [9, 10]. Interestingly, in the case of lung cancer, colon cancer, melanoma, glioblastoma, primary liver cancer, or multiple myeloma an increase of soluble forms of ICAM-1 and VCAM-1 (sICAM-1, sVCAM-1) levels in blood correlated with a higher clinical and morphological tumour stage [1, 3, 6, 8, 11–13].…”

Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients

“…The abnormal expression of ITGA2 has been correlated with unfavorable prognoses in multiple types of cancer. The nucleotide polymorphisms affecting adhesive molecules have been associated with the risk and prognosis of astrocytoma tumors (51).…”

Clinicopathological Findings and Five Year Survival Rates for Patients with Central Nervous System Tumors in Yazd, Iran

“…Cancer has an important and increasing role in the total disease load in the world (Thakkar et al, 2014). Cancer is regarded as onehistology (Mehta et al, 2011;Yilmaz et al, 2013). The brain like any other tissue of the body can bear neoplastic changes, but in the brain even benign neoplasms can cause complications as malignant tumors and this is because of the particular physiology and anatomy of the central nervous system (Sayegh et al, 2014).…”