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  • Title: CTLA-4 gene promoter and exon 1 polymorphisms in Iranian patients with gastric and colorectal cancers.
    Author: Hadinia A, Hossieni SV, Erfani N, Saberi-Firozi M, Fattahi MJ, Ghaderi A.
    Journal: J Gastroenterol Hepatol; 2007 Dec; 22(12):2283-7. PubMed ID: 18031393.
    Abstract:
    BACKGROUND AND AIM: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by down-regulating T-cell activation. Effects of several polymorphisms in CTLA-4 on CTLA-4 expression and function have been previously documented. The aim of this study was to investigate the putative effect of CTLA-4 polymorphisms on susceptibility to gastric and colorectal cancers in an Iranian population. METHODS: A total of 155 patients (109 with colorectal cancer and 46 with gastric cancer) and 190 age- and sex-matched healthy controls were evaluated. Genotyping of -1722T/C, -1661A/G, and +49A/G were performed by PCR restriction fragment length polymorphism methods and of -318C/T by a PCR amplification refractory mutation system technique. RESULTS: No statistically significant differences were found in the genotype distribution and allele frequencies among patients and controls. Haplotype analysis demonstrated that the TACG haplotype (-1722T, -1661A, -318C, +49G) frequency was significant increased in patients with colorectal cancer (P = 0.009) and gastric cancer (P = 0.006) in comparison to the control group. In contrast, the TACA haplotype frequency was significantly decreased in patients with colorectal cancer (P = 0.02) and not significantly decreased in patients with gastric cancer (P = 0.13) compared to the control group. CONCLUSION: A positive association between CTLA-4 TACG haplotype and gastric and colorectal cancers was found in an Iranian population. A protective role for TACA haplotype is postulated.
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