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Assessment of Early Genetic Changes in Smokers

18 Years
35 Years
Not Enrolling
Cancer of Head and Neck, Smoking

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Trial Information

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
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


Type of Study:


Study Design:

Observational Model: Case Control, Time Perspective: Prospective

Principal Investigator

Richard V Smith, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Montefiore Medical Center


United States: Federal Government

Study ID:




Start Date:

March 2004

Completion Date:

Related Keywords:

  • Cancer of Head and Neck
  • Smoking
  • cancer of head and neck
  • smoking
  • Head and Neck Neoplasms
  • Smoking



Montefiore Medical Center Bronx, New York  10467-2490