Association between survivin gene promoter -31G/C and -644C/T polymorphisms and non-small cell lung cancer.

Lung cancer is the most common cancer worldwide. Survivin is one of the first reported inhibitors of apoptosis proteins, which is an important family of proteins that regulate apoptosis. The survivin gene is located on human chromosome 17q25, which is composed of 142 amino acids. A common polymorphism of the survivin gene promoter -31G/C has been shown to influence cancer risk. This genetic variant has been associated with overexpression of survivin at both protein and mRNA levels in cancer cells. We examined promoter (-31G/C) genotype frequency in a patient group (N = 146), 77.4% GG, 18.5% GC, 4.1% CC, and in a control group (N = 98), 57.1% GG, 34.7% GC, 8.2% CC. These distributions were significantly different. Promoter (-644C/T) genotype frequency in the patient group was 40.4% TT, 48.6% TC, 11% CC, and in the control group it was 55.1% TT, 40.8% TC, 4.1% CC; these distributions were also significantly different. Individuals carrying the survivin 31 GC genotype and those carrying the survivin 644 CC genotype had a significantly decreased risk of having non-small cell lung cancer.

Lack of association between increased mitochondrial DNA4977 deletion and ATP levels of sputum cells from chronic obstructive pulmonary disease patients versus healthy smokers.

In this study we looked at smokers with and without chronic obstructive pulmonary disease (COPD) patients in order to evaluate the incidence of 4977 base pair (bp) mtDNA (mtDNA4977) deletion and mtDNA copy number in sputum cells and in peripheral blood leukocytes (PBLs) in relation to mitochondrial function and oxidative stress status. Twenty-five COPD patients who were current smokers, 22 smokers and 23 healthy nonsmokers (for only PBLs studies) participated in this study. The 4977-bp deletion was detected in all examined samples within 40 cyles of PCR amplification, using a quantitative real time PCR. The frequency of the mtDNA4977 was significantly higher in the sputum cells of patients with COPD compared to smokers without COPD (p < 0.0001). This difference was not observed in PBLs. Levels of cellular oxidative stress were significantly higher in the sputum cells of subjects with COPD than in the smoker group. However, mtDNA copy number, mitochondrial membrane potential (ΔΨm) and cellular ATP levels in PBLs and sputum cells were not significantly different between the studied groups. The Pearson analysis revealed no correlations between the accumulation of mtDNA4977, and intracellular ATP content and ΔΨm values of the sputum cells, although there was a positive correlation between the increase in the percentage of deleted mtDNA4977 and the levels of cellular oxidative stress in COPD patients (r = 0.80, p < 0.0001). Our studies may suggest that the accumulation of mtDNA4977 in the sputum cells of smokers with COPD does not seem to have an important impact on mitochondrial dysfunction in relation to ATP production and ΔΨm when compared to those of healthy smokers.

Investigation of NF-κB1 and NF-κBIA gene polymorphism in non-small cell lung cancer.

Lung cancer is a complex, multifactorial disease which is the leading cause of cancer death in both men and women. NF-κB is a transcription factor which is known to affect the expression of more than 150 genes related to inflammation, lymphocyte activation, cell proliferation, differentiation, and apoptosis, as well as contributing to cell apoptosis and survival. However, NF-κBIA (IκBα) is the inhibitor of the transcription factor. The--94ins/delATTG polymorphism of the NF-κB1 gene promoter region which causes a functional effect and NF-κBIA 3'UTR A → G polymorphism has been shown to be related to various inflammatory diseases and cancer. Ninety-five NSCLC patients and 99 healthy controls were included in study. The NF-κB1-94ins/delATTG and NF-κBIA 3'UTR A → G polymorphism have been studied by using PCR-RFLP method. It was found that the NF-κB1 -94ins/delATTG DD genotype and D allele frequencies were higher in patients than healthy controls and the presence of the DD genotype has a 3.5-fold increased risk of the disease (P: 0.014). This study is the first to investigate the NF-κB1-94ins/delATTG and NF-κBIA 3'UTR A → G polymorphism together in the Turkish population. According to the results, the NF-κB1-94ins/del ATTG promoter polymorphism may have a role in lung carcinogenesis and prognosis.

Identification of a differential expression signature associated with tumorigenesis and metastasis of laryngeal carcinoma.

OBJECTIVES: Metastasis is the most significant prognostic factor for laryngeal carcinoma which necessitates the identification of molecular alterations associated with metastasis. The identification of such molecular alterations will not only prove useful in treatment but also provide insight into mechanisms of cancer metastasis. The studies conducted so far have not specifically focused on metastasis or invasion pathways. Therefore we investigated the expression profiles with a pathway focused approach. MATERIALS AND METHODS: Total RNA was extracted from 36 laryngeal tumors and paired cancer free tissue. Expression levels of 88 genes were determined using a PCR array system following cDNA synthesis. Obtained data was used for the calculation of altered expression levels, facilitating relevant algorithms. Significant alterations were determined according to their p-value obtained by Student's t-test. RESULTS: Sixteen genes have shown altered expression when compared with adjacent cancer-free tissue. 2 of these 16 genes have shown differential expression in tumors with neck metastasis in respect to non-metastatic tumors. CONCLUSION: We found that TGFB1, TIMP1, c-Myc, SPARC, COL4A2 and SOX4 show altered expression in laryngeal tumors. c-Myc and SOX4 expression is decreased as laryngeal tumors switch to metastatic phenotype.