CTLA-4 Exon One +49A/G Gene Variants in Patients with Superficial and Invasive Bladder Cancer: A Study in Southern Iran

Cytotoxic T-cell lymphocyte antigen 4 (CTLA-4) is a member ofthe superfamily of immunoglobulins that are mainly expressed by activated T cells.It is established that blockade of CTLA-4 receptors leads to the enhancement of animmune response. Different polymorphisms of the CTLA-4 gene have been describedwhich cause increased susceptibility to various malignancies such as lymphoma ormultiple myeloma. Considering that bladder cancer is one of the most prevalent cancersworldwide, we have evaluated the role of CTLA-4 gene polymorphism at position+49 A/G in the formation or progression of bladder cancer in southern Iran. Atotal of 226 individuals between February 2005 andJune 2006 were included and placed into two subgroups: patients diagnosed withbladder cancer and a control group. Demographic data and risk factors were collectedfrom both groups. The DNA of all subjects was extracted from their blood samples.Different genotypes of the CTLA-4 gene were determined using the restrictionfragment length polymorphism (RFLP) technique and data were compared in bothgroups by using Pearson''s chi-square test. The prevalence of AA, AG and GG genotypes at position 49, accordingto the PCR-RFLP method, were 57.5%, 37.2% and 5.3% in the control group,respectively. In the patient group, the prevalence of these genotypes was: AAin 57.5%,AG in 32.7% and GG in 9.8%. Statistical analysis of data showed no significantdifference in both groups (P value=0.40). Also there was no correlation betweendifferent genotypes of the CTLA-4 gene and invasiveness of the disease in ourcases. Although polymorphism of the CTLA-4 gene at position 49 ofexon-1 increases susceptibility to several malignancies, our study showed norelationship between polymorphism at this position and genetic susceptibility to thedevelopment of bladder cancer, nor was there any association with disease progression.