Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00200408
Status:
TERMINATED
Last Update Posted:
2015-04-08
First Post:
2005-09-13
Brief Title:
Assessment of Early Genetic Changes in Smokers
Sponsor:
Montefiore Medical Center
Organization:
Montefiore Medical Center
Study Overview
Official Title:
Assessment of Early Genetic Changes in Smokers
Status:
TERMINATED
Status Verified Date:
2015-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
unable to obtain funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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 benzoapyrene 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 dont
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
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 benzoapyrene 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 dont
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None