Assessment of Early Genetic Changes in Smokers

April 7, 2015 updated by: Montefiore Medical Center

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.

Study Overview

Status

Terminated

Conditions

Detailed Description

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:

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.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- New York
  - Bronx, New York, United States, 10467
    - Montefiore Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

healthy smokers and non-smokers

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Case-Control
Time Perspectives: Prospective

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
smokers college students who smoke
non smokers college students who don't smoke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
alteration of gene expression profile Time Frame: 2 yrs	comparison of gene expression profiles between smokers and non-smokers	2 yrs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Investigators

Study Chair: Richard V Smith, MD, Montefiore Medical Center
Principal Investigator: Thomas Belbin, PhD, Albert Einstein College of Medicine
Principal Investigator: Nicholas Schlecht, PhD, Albert Einstein College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2004

Primary Completion (Actual)

January 1, 2005

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria