CTLA-4 Gene +49 A/G Polymorphism in Prostate Cancer Patients in Turkish Population

Cancer is a multifactorial disease caused by complex interactions between the genetic and environmental factors [1]. Prostate cancer (PCa) is the most common malignancy in man worldwide and its rate is increasing in both developed and developing countries [2]. The etiology of cancer is complicated and not exactly known. For this reason, recent studies have focused on the role of the immune system. There are two important steps in tumorigenesis that include the abduction of immune surveillance by tumor cells and the generation of immunosuppressive cytokines. Therefore, tumor immunity is known as a hot spot in cancer research. The most significant antitumor reply is cell-mediated and includes T lymphocytes and the natural killer (NK) cells. Therefore, genetic polymorphisms in the human genome regulating the activation and proliferation of T lymphocytes and NK cells may influence the risk of cancer [1]. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is located in chromosome 2 (2q33) [3]. Single nucleotide polymorphisms (SNPs) in the CTLA-4 gene have been linked to the sensitivity to autoimmune disease, but, the studies conducted in recent years suggested that the 49A/G polymorphisms in CTLA-4 are risk factors for cancer. Many (>100) SNPs have been identified in the CTLA-4 gene that contains three exons and two introns. Some of these are, the -318C/T SNP (rs5742909) located in the promoter region, the 49A/G SNP (rs231775) located in exon 1, and the 6230A/G SNP (CT60, rs3087243) located in 3’-untranslated region (3’UTR) [1,4]. Many studies demonstrated that these 3 (the CTLA-4 gene +49A/G, the CTLA-4 gene -318C/T, and the CTLA-4 gene 6230A/G) polymorphisms were involved in the etiology of various cancers, including cervical cancer, lung cancer, breast cancer, hepatocellular cancer, and osteosarcoma [5-8]. In addition, in many epidemiologic studies conducted so far, the 49A/G SNP (rs231775) in the CTLA-4 that causes a threoninetoalanine substitution in codon 17 has been found to be associated with genetic susceptibility to cancer in several populations [1,4,9]. The different polymorphisms in CTLA-4 gene have been analyzed on patients with inflammatory bowel disease [10-12], diabetes [13-15] and various cancer [5,8,16]. Therefore, we aimed at investigating the significance of CTLA-4 gene +49 A/G single nucleotide polymorphisms in patients diagnosed with prostate cancer in this study.