Assessment of Early Genetic Changes in Smokers
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.
Cancer of Head and Neck
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Assessment of Early Genetic Changes in Smokers|
|Study Start Date:||March 2004|
|Primary Completion Date:||January 2005 (Final data collection date for primary outcome measure)|
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:
- Test the hypothesis that there are specific genetic alterations, leading to gene expression profile changes, which will be detected in early smokers.
- Test the hypothesis that early smokers will demonstrate alterations in global DNA methylation patterns compared to matched controls.
- To analyze gene alterations and DNA methylation in college smokers over time through longitudinal follow-up.
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10467|
|Study Chair:||Richard V Smith, MD||Montefiore Medical Center|
|Principal Investigator:||Thomas Belbin, PhD||Albert Einstein College of Medicine of Yeshiva University|
|Principal Investigator:||Nicholas Schlecht, PhD||Albert Einstein College of Medicine of Yeshiva University|