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.
