Volume 22, Issue 12 pp. 2283-2287

CTLA-4 gene promoter and exon 1 polymorphisms in Iranian patients with gastric and colorectal cancers

Abolghasem Hadinia

Abolghasem Hadinia

Departments of Immunology,

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Seyed Vahid Hossieni

Seyed Vahid Hossieni

Surgery and

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Nasrollah Erfani

Nasrollah Erfani

Departments of Immunology,

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Mehdi Saberi-Firozi

Mehdi Saberi-Firozi

Internal Medicine, and

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Mohammad Javad Fattahi

Mohammad Javad Fattahi

Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran

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Abbas Ghaderi

Corresponding Author

Abbas Ghaderi

Departments of Immunology,

Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran

Professor Abbas Ghaderi, Department of Immunology, Shiraz Institute for Cancer Research, PO Box 71345-1798, Shiraz, Iran. Email: [email protected]Search for more papers by this author
First published: 19 November 2007
Citations: 58

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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