Assessment of Early Genetic Changes in Smokers
Our pilot study using cDNA microarrays to examine the buccal mucosa of smokers and
non-smokers demonstrated that smokers could be separated from non-smokers based solely on
the patterns of gene expression observed. We were able to identify 924 genes whose
expression differs significantly between samples from smokers and non-smokers. Several genes
were also shown to be either up or down regulated in our earlier research applying
microarray analysis to head and neck cancer tumors. Many of these represent genes of
possible interest as early molecular markers for head and neck carcinogenesis.
Aberrant methylation is an important event in the transcriptional silencing of candidate
tumor suppressor genes in smoking associated malignancies. Furthermore, it is known that
methylated CpG islands are the preferred binding site for benzo(a)pyrene diol epoxide and
other carcinogens found in tobacco smoke. Binding of these compounds is known to cause DNA
adducts and transversion mutations that are often observed in the aerodigestive tumors of
smokers. New evidence suggests that specific DNA methylation events are directly linked to
tobacco use. The ability to detect such molecular markers during screening of high risk
groups would represent a significant advance in cancer screening and early detection. Our
group has evaluated specimens to epigenetically profile CpG island hypermethylation in HNSCC
tumor samples using a technique known as methylation specific restriction enzyme microarray
analysis. This method will be used in this trial to detect alterations in global DNA
methylation patterns in subjects who smoke compared to those who don't.
The objectives of this study are:
1. Test the hypothesis that there are specific genetic alterations, leading to gene
expression profile changes, which will be detected in early smokers.
2. Test the hypothesis that early smokers will demonstrate alterations in global DNA
methylation patterns compared to matched controls.
3. To analyze gene alterations and DNA methylation in college smokers over time through
Observational Model: Case Control, Time Perspective: Prospective
Richard V Smith, MD
Montefiore Medical Center
United States: Federal Government
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