Serum levels of interleukin-7 and interleukin-8 in head and neck squamous cell carcinoma.

Background: The aim of this study was to investigate the association of head and neck squamous cell carcinoma (HNSCC) with serum levels of interleukin-7 (IL-7) and IL-8, the two cytokines whose associations with HNSCC need more clarifications. Materials and Methods: Commercial enzyme-linked immunosorbent assay kits were used for the quantification of the cytokines. Sera were collected from 48 untreated patients (36 men and 12 women; mean age: 52.7 ± 9.8 years) and 34 healthy donors (26 men and 8 women; mean age: 53.1 ± 9.0 years). Results: Serum IL-8 level was neither significantly different between HNSCC patients and control individuals nor associated with smoking status, gender, age, tumor location, tumor grade, and stage of the patients (P > 0.05). Regarding IL-7, all control individuals had serum levels below the sensitivity of the kit (3 pg/ml), but nine patients had detectable levels, and that the mean serum IL-7 was significantly higher in the patients compared to the controls (P = 0.008). Conclusions: Serum IL-8 level is not significantly associated with HNSCC. With the sensitivity of the kit we employed, it seems that serum IL-7 levels are specifically elevated in HNSCC patients compared to healthy individuals. Data from other independent studies are required to clarify the possible employment of IL-7 as an HNSCC biomarker.

Serum levels of interleukins 4 and 10 in head and neck squamous cell carcinoma.

OBJECTIVE: There is currently controversy over the association between serum interleukin-4 and -10 levels and head and neck squamous cell carcinoma in patients of different ethnicity. This study aimed to investigate serum levels of these cytokines in Iranian patients with this pathology, and to analyse correlations with tumour location and tumour stage at diagnosis. DESIGN: Serum cytokines levels were quantified using commercial enzyme-linked immunosorbent assays. SUBJECTS: Study groups comprised 93 untreated patients and 53 healthy donors. RESULTS: Serum interleukin-4 levels were significantly increased in patients compared with controls (p < 0.000), but were not significantly associated with tumour stage. Serum interleukin-10 levels were not raised in patients, nor associated with tumour stage. CONCLUSION: Serum levels of interleukin-4, but not -10, were increased in Iranian head and neck squamous cell carcinoma patients. These data do not support an association of these cytokines with tumour progression; this is consistent with previous findings.

p 53 codon 72 polymorphism in stomach and colorectal adenocarcinomas in Iranian patients.

BACKGROUND: The association of a functional single nucleotide polymorphism at codon 72 of the p53 gene (Arg72Pro) with malignancy is a subject of controversy. We analyzed this polymorphism in 224 patients with gastrointestinal cancers (92 with stomach cancer and 132 with colorectal cancer) and in 163 healthy controls. MATERIAL AND METHODS: DNA was extracted from peripheral blood mononuclear cells and amplified with an allele-specific polymerase chain reaction. RESULTS: There was no significant association between p53 alleles and gastrointestinal cancers. The frequency of the Arg allele was 59.7, 58.8, and 59.2% in the stomach cancer patients, colorectal cancer patients, and controls, respectively. Frequencies of the Pro allele were 40.3% in patients with stomach cancer, 41.2% in patients with colorectal cancer, and 40.8% in controls. Likewise, genotype frequencies did not differ significantly between the two patient groups and controls. There were no differences in genotype or allele frequencies by gender, age, or histological grade. CONCLUSIONS: The data do not support the association of the p53 codon 72 polymorphism with stomach or colorectal cancers in Iranian patients.

Association of interleukin-18 gene promoter polymorphisms with breast cancer.

Interleukin-18 [IL-18] gene promoter polymorphism is reported to be a genetic risk factor for several types of cancer. The aims of this investigation were to evaluate and compare the frequencies of IL-18 gene promoter polymorphisms at positions -137 [G/C] and -607 [C/A] in breast cancer patients and healthy controls as well as to study the contribution of these data with clinicopathological parameters at diagnosis. The studied populations comprised 250 cases with breast carcinoma and 206 healthy subjects. IL-18 gene promoter polymorphisms at positions -137 and -607 were amplified in patient and control groups using allele specific polymerase chain reaction [AS-PCR]. The frequencies of GG, GC and CC genotypes of -137 SNP were 141 [56.4%], 96 [38.4%] and 13 [5.2%] in patients vs. 110 [53.4%], 72 [34.9%] and 24 [11.7%] in controls, respectively. A significant decrease of the CC genotype was observed in patients [p = 0.04]. The frequency of the CC genotype at position -137 was also significantly higher in patients with metastasis than non-metastatic patients [21.4% vs. 4.3%] [p = 0.02]. There was no significant association between genotype frequencies at position -607 with breast cancer or its clinicopathological parameters at diagnosis. Moreover, allelic frequencies at these positions did not contribute to breast cancer incidence. The distribution of IL-18 gene haplotypes and genotype combinations were not significantly different between patients and normal control individuals. This is the first report investigating the contribution of IL-18 gene promoter polymorphisms to breast cancer. These results suggest contrast effects of IL-18 gene in cancer induction and progression. Key words: Breast cancer, IL-18, polymorphism.

Head and neck squamous cell carcinoma is not associated with interleukin-18 promoter gene polymorphisms: a case-control study.

OBJECTIVE: To investigate the association of two functional single nucleotide polymorphisms in the promoter region of the interleukin-18 gene, at positions -607 and -137, with head and neck squamous cell carcinoma. DESIGN: Genomic deoxyribonucleic acid was extracted, by the salting-out method, from peripheral blood leukocytes. Single nucleotide polymorphisms of the interleukin-18 gene at positions -607 (cytosine/adenine) and -137 (guanine/cytosine) were analysed by sequence-specific polymerase chain reaction. SUBJECTS: One hundred and eleven patients (86 men and 25 women; mean age 56.7+/-13.7 years) and 212 regional controls (165 men and 47 women; mean age 53.3+/-12.2 years) were studied. Control subjects comprised healthy volunteers or cancer-free individuals presenting with otolaryngological disease. The diagnosis of squamous cell carcinoma was confirmed histopathologically. Various clinical parameters were collected at diagnosis, including tumour site, tumour size, lymph node involvement, distant metastasis and stage. RESULTS: There was no significant association between the allele, genotype or haplotype frequencies of the two single nucleotide polymorphisms of the interleukin-18 promoter and the head and neck squamous cell carcinoma susceptibility or clinical parameters at diagnosis. CONCLUSION: Interleukin-18 polymorphisms at positions -607 and -137 did not confer susceptibility to head and neck squamous cell carcinoma in southern Iranian patients.

Association of chemokine receptor 5 (CCR5) delta32 mutation with Behçet's disease is dependent on gender in Iranian patients.

OBJECTIVE: Behçet's disease (BD) is a recurrent multi-system inflammatory disorder caused by the combinations of multiple genetic and environmental factors. CCR5 is a Th1-dominant chemokine receptor whose levels are increased in patients with active BD. It is believed that a 32 bp deletion in the CCR5 gene reduces the expression of this receptor on the cell surface. The aim of the present study was to investigate the association of CCR5 delta32 allele with BD in Iranian patients. METHODS: The study included 100 patients with BD and 380 healthy controls. Polymerase chain reaction (PCR) amplification was used for analysis of CCR5 delta32 allele. RESULTS: The frequency of CCR5 delta32 allele was not statistically different between 100 patients with BD and 380 healthy individuals. However, categorizing patients according to gender revealed a significant difference in distribution of the CCR5 delta32 allele in female patients compared with female control individuals (p = 0.047, fisher's exact test, OR = 2.66). CONCLUSION: The results suggest that the CCR5 delta32 allele may be a genetic risk factor for BD in Iranian women. These results warrant further investigation to clarify the underlying mechanism of CCR5 deficiency in the initiation of BD.

Association of CTLA-4 gene promoter polymorphisms with systemic sclerosis in Iranian population.

In a recent study, we were unable to show any association between CTLA-4 exon-1 polymorphism and systemic sclerosis (SSc) in Iranian population. In order to further explore the role of this immune inhibitory gene in SSc development, in the present study, the polymorphisms in the CTLA-4 promoter region (-1,722 T/C, -1,661 A/G and -318 C/T) were investigated in 83 SSc patients and 166 healthy controls. All genotypes and allele frequencies in patients were significantly different from the control group (P=0.022 for -1,722 T/C, P=0.03 for -1,661 A/G and P=0.014 for -318 C/T genotypes). The -1,722C, -1,661G and -318T alleles contributed to SSc with P=0.012, odds ratio (OR) 2.16, P=0.031, OR 1.82 and P=0.023, OR 2.45, respectively. A significant difference was observed in the frequency homozygous 'genotype combination' -1,722TT/-1,661AA/-318CC of these three polymorphisms (P(c)=0.003). The frequency of this genotype combination was significantly higher in the control group than in patients. Results of this investigation indicate that -1,722C, -1,661G and -318T alleles of CTLA-4 gene promoter appear to be associated with SSc, and individuals carrying these alleles may be more susceptible to this disease.

Association of IL-18 promoter polymorphisms with predisposition to Type 1 diabetes.

AIMS: IL-18, a potent IFN-gamma-inducing cytokine, is capable of polarizing the immune response to a Th1 phenotype. Recent studies have demonstrated an association between single-nucleotide polymorphisms located at positions -607 (A/C) and -137 (C/G) in the promoter region of IL-18 gene and Type 1 diabetes. The aim of the present study was to determine whether the same polymorphisms of the gene were associated with Type 1 diabetes in Iranians. METHODS: In 112 patients with Type 1 diabetes and 194 non-diabetic control subjects, these two single-nucleotide polymorphisms were analysed by sequence-specific PCR. RESULTS: Allele and genotype frequencies of the IL-18 gene polymorphisms were similar in the whole group of Type 1 diabetic patients and controls. However, categorizing patients according to age at onset of diabetes revealed a significant difference in distribution of the genotypes at position -137 between patients with older age at onset (> 15 years) (GG 49%, GC 34%, CC 17%) and control subjects (GG 57.7%, GC 36.6%, CC 5.7%) (P = 0.027). Frequency of the C allele at position -137 was significantly higher in these patients than in controls (P = 0.038). Moreover, there was an association between -607AA/-137CC genotype combination and susceptibility to Type 1 diabetes in this subgroup of patients (pc = 0.027). CONCLUSIONS: The results of this study show that polymorphisms of IL-18 promoter confer susceptibility to Type 1 diabetes in Iranian individuals with onset at older ages. Further investigations are necessary to clarify the effect of IL-18 variants on immune regulation.