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


CONCLUSIONS
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.
Hadinia
Abolghasem
A
Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
Hossieni
Seyed Vahid
SV
Erfani
Nasrollah
N
Saberi-Firozi
Mehdi
M
Fattahi
Mohammad Javad
MJ
Ghaderi
Abbas
A
D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human