Aberrant methylation of p16 and MGMT genes in lebanese smokers. (c2005)

Abstract

Recent studies have demonstrated that aberrant methylation of p16 (tumor suppressor gene) and / or MGMT gene (DNA repair enzyme) is detected in DNA samples from sputum in 100% of patients with squamous cell carcinoma as early as 3 years before clinical diagnosis. Moreover, the prevalence of these markers in sputum from cancer-free, high-risk subjects approximates lifetime risk for lung cancer. Knowing that the casual relationship between smoking and lung cancer is well established and that 90 percent of all lung cancer deaths can be attributed to smoking, the goal of my research was to assess the methylation status of p16 and MGMT genes in a controlled population of smokers versus a control population of non smokers. Accordingly, sputum samples were collected randomly from 198 people; 102 smokers and 96 non-smokers in sterile specimen cups and were subjected to molecular genetic analysis. Aberrant promoter methylation ofp16 was seen in 73.33% of smokers above 40 years old, and in 8.7 % of smokers below 26 years old, where as methylation of MGMT was not detected at all. As for non smokers, methylation of p16 gene was detected in 4 % of controls above 40 years old and non below 26 years old where as methylation of MGMF was detected in only one case. The strong association seen between p16 methylation and smokers seems to offer a potentially strong approach to population - based screening for the early detection of lung cancer, and possibly other forms of human cancer.