unable to obtain funding

This study will look at the genetic profile of cells taken from the oral cavity of healthy college students who smoke and who do not smoke cigarettes. This will be done using a small brush similar to that used in Pap tests for cervical cancer detection. Our aim is to determine if smoking causes early genetic changes in the DNA of these cells such as have been seen in the cells of cancerous tumors of the head and neck area and nearby healthy tissues. This will be correlated with data from subject questionnaires to assess tobacco use, and other behavior and demographic information.

Our pilot study using cellular DNA (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. head and neck squamous cell carcinoma ( 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 longitudinal follow-up.

Inclusion Criteria:

College freshmen and sophomores

Smokers must be between the ages of 18 and 25

Smokers must have smoked regularly for at least 2 years and be currently smoking

Smokers must intend to stay in the New York area for at least 3 years.

Non-smokers must be non-users of marijuana -

Exclusion Criteria:

Current HIV/AIDS infection

Use of chewing tobacco

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healthy smokers and non-smokers