Changes in Mouth Signal Lung Cancer
CancerWise - June 2008
Smoking silences two cancer-fighting genes in the tissue lining the inside of the mouth, which could enable earlier, easier detection of lung cancer, according to a study reported at the annual meeting of the American Association for Cancer Research in April.
Significance of results
"Our study provides the first systematic evidence that accessible tissue, the oral epithelium, can be used to monitor molecular events in the less accessible tissue of the lungs of chronic smokers," says first author Manisha Bhutani, M.D., post-doctoral fellow in M. D. Anderson’s Department of Thoracic/Head and Neck Medical Oncology. "We are talking about just a brushing inside of the cheek to get the same information we would from taking a tissue sample from the lung."
The team took samples of epithelial tissue from the mouths and lungs of 125 chronic smokers enrolled in a large, prospective lung cancer chemoprevention study. They obtained second samples three months later.
The behavior of two crucial tumor-suppressing genes that are damaged or silenced early in cancer development was analyzed.
The genes were:
The researchers tracked whether p16, FHIT or both had been silenced by methylation, the attachment of a methyl group – a carbon atom surrounded by hydrogen atoms – that then shuts down its function. Patterns of methylation were compared between the tissues from the lung and mouth of each smoker.
The lung tissue comparisons showed methylation of:
- p16 in 23% of study participants
- FHIT in 17% of study participants
- Either gene in 35% of study participants
The mouth tissue comparisons showed methylation of:
- p16 in 19% of study participants
- FHIT in 15% of study participants
- Either gene in 31% of study participants
Strong correlations were observed between methylation patterns in both the mouth and lung tissue. When either gene was methylated in mouth lining tissue, 95% of the participants had methylation in lung tissue, too.
When methylation was not present in the mouth tissue, 69% of participants were found to have methylation in lung tissue.
Similar correlations were seen at the three-month analysis.
One follow-up area of study is to find additional biomarkers in oral tissue.
"Our study opens the door to enhancing our ability to predict who has higher probability of getting tobacco-related cancers, such as pancreatic, bladder, and head and neck cancers," says senior researcher Li Mao, M.D., professor in
M. D. Anderson's Department of Thoracic/Head and Neck Medical Oncology.
- Adapted by Dawn Dorsey from an M. D. Anderson news release