Features of DNA reparative synthesis and gene polymorphism of biotransformation enzymes of xenobiotics in lung cancer patients

Abstract

This paper shows results of comparative study of DNA reparation system and gene polymorphism of biotransformation enzymes of xenobiotics in patients with lung cancer (LC), chronic obstructive pulmonary disease (COPD) and healthy adults. We examined 50 patients with central LC: 41 males, 9 females with the average age of 56.57 ± 7.96 yrs treated in Oncology Research Institute in Tomsk. Comparative groups involved 46 chronic bronchitis patients with preneoplastic lesions of bronchial epithelium proved by morphologic and endoscopic examinations and 50 healthy men of the same age without respiratory pathology. Cell reparative activity was studied in blood lymphocytes. DNA samples of the LC and COPD patients were typed for polymorphism of GSTT1, GSTM1 and CYP2C19 biotransformation genes. The results showed reduced functional activity of DNA reparation systems as well as in chronic bronchitis patients and LC patients. Investigation of DNA reparative synthesis intensity revealed significant inhibition of this process in most of the LC patients. This intensity was related to a histological type of the tumour and its stage. The LC patients had decreased rate of the GSTM1 null genotype that could be specific for this pathology. The genotype spread in the LC patients greatly differed from that in healthy (p = 0.047) but the spread in the COPD patients was close to that in healthy. A difference between the LC patients and COPD patients was not found because of a small size of the groups. Thus, studies with larger sizes are required. Practical importance of such studies could be development of genotyping test sets to predict an increased risk for neoplasm occurrence.