Investigation of CTLA‐4 and CD28 gene polymorphisms in a group of Turkish patients with colorectal cancer

Abstract

Colorectal cancer (CRC), also called colon cancer or bowel cancer, includes cancerous growths in the colon, rectum and appendix. The immune system is an important defence mechanism against cancer and is often dysfunctional in patients with malignancies. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and CD28 genes encode receptors that provide negative and positive signals, respectively. Polymorphisms in these genes can affect their functions. In this study, we aimed to investigate the association of cancer with the frequencies and roles of CTLA-4/+49A > G (exon 1) and -318C > T (promoter), and CD28/IVS3 + 17T > C (intron 3 position + 17). These polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 218 Turkish subjects (56 patients with CRC and 162 healthy controls). No statistically significant differences in the genotype distributions of CTLA-4/+49GG (1.8% vs. 6.8%, odds ratio (OR) = 0.250, P = 0.305) and CTLA-4/-318TT (0% vs. 0.6%, OR = 1.006, P = 1.000), and CD28/IVS3 + 17CC (8.9% vs. 3.7%, OR = 0.2411, P = 0.155) between patients with CRC and healthy controls, were observed. We also found that there were no significant differences in the frequencies of CTLA-4/+49G (18.8% vs. 20.1%, OR = 0.920, P = 0.891) and CTLA-4/-318T (7.1% vs. 4.3%, OR = 1.653, P = 0.314), and CD28/IVS3 + 17C alleles (25.9% vs. 19.1%, OR = 1.353, P = 0.139) between two study groups. Present results suggested that CTLA-4 and CD28 gene polymorphisms did not play an important role in Turkish patients with CRC.

Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?

“…Moreover, it was found by us and others that the same allele confers susceptibility to female-related cancers: sporadic breast cancer [31,48], and cervical cancer [29,32] as well as non-small cell lung cancer in women [24]. In contrast to our results CTLA-4g.319C>T polymorphism was not associated with lung cancer (without stratification by gender) [41] or other cancers, such as colon cancer [42], colorectal cancer [52] or multiple myeloma [44]. The meta-analysis performed by Zhang et al [49] indicated this polymorphism as related to cancer risk in the Europeans.…”

Lack of any Association of the CTLA-4 +49 G/A Polymorphism with Breast Cancer Risk in a North Indian Population

“…Ethnic disparities like these do exist with respect to the prevalence of a polymorphism in a particular ethnic population and its association with a disease (Mandal et al, 2010). For example, CTLA-4 +49 G/A polymorphism is known to be associated with the risk of colorectal cancer in Chinese but no such association was seen in a study on Turkish patients (Dilmec et al, 2008;Qi et al, 2010). This SNP was also found to be not associated with colorectal neoplasm among Italian Caucasians (Solerio et al, 2005).…”

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

“…Taq1 gene polymorphism genotypes frequencies differ among different ethnicities, different cancer types (Bid et al, 2005), and methodology by which Taq1 VDR polymorphism was investigated, sample size and vitamin D serum levels (Onen et al, 2008). Among Indian individuals the frequencies of Taq1 variants were 49%, 43% and 8% (Bhanushali et al, 2010) while Japanese study showed 77%, 22% and 1% (Minamitani et al, 1998) and a Turkish, study showed frequency of 40.8%, 47.9% and 11.2% (Dilmec et al, 2009) for TT, Tt and tt respectively.…”