IL-18 serum level and IL-18 promoter gene polymorphism in Iranian patients with gastrointestinal cancers.

BACKGROUND AND AIM: Interleukin (IL)-18 level and association of its two promoter gene polymorphisms at -607 C/A and -137 G/C positions were investigated in Iranian patients with gastrointestinal (GI) cancers. METHODS: 232 cases of GI cancers and 312 healthy controls were enrolled. Serum level of IL-18 was measured by enzyme linked immunosorbent assay (ELISA) and genotyping of IL-18 gene polymorphisms were assessed by allele-specific polymerase chain reaction (PCR). RESULTS: There was a significant difference in the frequency of -137 G/C genotype between patients with stomach or colorectal cancers and control group. In patients with colorectal cancer, the frequency of the -607 AA/-137 GC genotype combination in unwell-differentiated cases was more than those with well-differentiated cancer. Haplotype analysis showed that in patients with stomach cancer -607 C/-137 C and -607 A/-137 G and in patients with colorectal cancer -607 C/-137 C were decreased compared with control group, and this difference reached statistical significance. Serum analysis revealed that the mean IL-18 serum level in stomach and colorectal cancer before and after surgical operation was significantly higher than healthy volunteers. Postoperative IL-18 level for all patients with colorectal cancer was significantly decreased compared with the levels before surgery. CONCLUSION: Results of this investigation suggests that Single Nucleotide Polymorphism (SNP) at position -137 G/C and haplotype frequency may play a role in predisposition of Iranian patients to stomach and colorectal cancers. In addition, increasing serum IL-18 level may have clinical importance as a diagnostic marker in patients with stomach and colorectal cancer.

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

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.