Investigation of chromosomal aberrations and cell death receptor-4 polymorphisms in lung cancer patients

Lung cancer (LC) is the most common cause of death after hearth diseases and constitute 28% of cancer deaths and is a multifactorial disease. It increases with aging and most frequently occurs at 50-70 years. The most common cause of LC is smoking but also exposed to smoke, radon, working causes, diet, chronic lung diseases, air pollution and sex. Genetic factors are also effective in development of LC. So far, it was not identified any gene of chromosomal region responsible from LC. It is known that innumerable chromosomal aberration occurs in tumor progression.In organisms, it was known that cellular death occurs through a transmembrane protein called cell death receptor-4 (DR4). It is located at 8p21-22 region and allellic losses of this region was reported previously in various cancer type. Some abnormalities in gene coded this protein effect cell signalization and result with not cell death and cancer development. Four different polymorphisms (G422A, C626G, A683C ve A1322G) occured in this gene are effective in development of LC and other cancers, and determination the therapy form with chemotherapeutic drugs.In our study, 60 patients refered to University of Çukurova, Faculty of Medicine, Chest Diseases Polyclinic for LC pre-diagnosis and 30 controls who are smoker, healthy and not having any lung diseases were scanned cytogenetically and DR4 gene polymorphisms were also analysed. In cytogenetic studies, standard cytogenetic procedures were applicated. For determination of DR4 gene polymorphisms, PCR-RFLP and PCR-ARMS technics were used. Sequence analysis was applied if necessary.In our study, hot spots at 1p36, 1q23, 1p33, 1q11, 1q31, 3p, 7p, 7q22, 9p, 9q, 10p, 10q22, 10q24, 11p12-13, 11q21, 11q23, 12q13, 12q15, 12q24 and Xq26 regions were reported after tissue and blood cytogenetic analysises. Also, sex and autosomal chromosome aneuploidies were found frequently. Thus, it was thought that this chromosomes and regions should be investigated first for identifing genes responsible from LC.When we looked the DR4 gene polymorphisms in patient and control groups, it was found that they have carried the G422A and C626G heterozygote frequently (56,7% ve 40% for the two region, respectively). For A683C and A1322G, it was seen that the both groups carried AA genotype at these regions in high proportion (for A683C, 68,3% and 70%; for A1322G, 88,3% and 80%, respectively). There is not any significant differences for the four regions (p>0,05). But CC genotype in exon 5, for A683C region, and GG genotype in exon 10, for A1322G region may be important, and can be said that these genotypes may do normal TRAIL signalization rather than TRAIL resistance; thus, these genotypes may increase the TRAIL efficiency with chemotherapeutic drugs in LC treatment. Because of these reasons, it was thought that most of patients and other exons should be analyzed.