Oral Epithelium As A Surrogate Tissue For Assessing Smoking-Induced Molecular Alterations In The Lungs

Main Category: Lung Cancer
Also Included In: Respiratory / Asthma;  Cancer / Oncology
Article Date: 17 Apr 2008 - 3:00 PDT

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Doctors may be able to determine the extent of a smoker's lung damage by looking in his or her mouth, according to new research from The University of Texas M. D. Anderson Cancer Center.

Because smoking exposes both the lungs and oral cavity to tobacco carcinogens, the scientists hypothesized that cells lining the mouth undergo molecular alterations similar to those in other parts of the airway and therefore could be used as surrogate tissue to assess molecular damage to the lungs, says senior study author Li Mao, M.D., a professor of thoracic/head and neck medical oncology and of systems biology at M. D. Anderson.

Mao and colleagues, analyzing lung and mouth tissue samples from 125 chronic smokers enrolled in a cancer prevention trial, found similar molecular changes in both types of tissue.

"Our study provides the first systematic evidence that readily accessible tissue from the mouth can be used to monitor molecular events in inaccessible tissue like the lungs, offering a convenient biomonitoring method to provide insight into the molecular events that take place in lungs of chronic smokers," Mao said. "An oral brush is easy to obtain and noninvasive; it allows us to test for lung damage without having to do a bronchoscopy."

Using a laboratory technique called methylation-specific polymerase chain reaction, which enables the production of millions of copies of a specific DNA sequence in a short period of time, the researchers analyzed promoter methylation (a DNA modification that shuts down gene expression) of the tumor suppressor genes p16 and FHIT in 1,774 samples of oral and bronchial tissue taken from the study participants. They found that methylation patterns observed in the oral tissues correlated with those observed for bronchial tissues.

At the study's start, researchers observed promoter methylation in 23 percent of bronchial tissues and 19 percent of oral tissues for p16; 17 percent of bronchial tissues and 15 percent of oral tissues for FHIT; and 35 percent of bronchial tissues and 31 percent of oral tissues for any combination of the two genes. Among the 39 participants with oral tissue methylation in both genes, the average bronchial methylation index was 0.52 (meaning 52 percent of tissues sampled had molecular changes), compared to 0.27 for the 86 cases without oral tissue methylation.

Similar correlations were observed in tissue samples obtained three months later.

Mao says it is possible that oral tissue may contain other molecular signatures that predict the presence of primary lung cancer but also other aerodigestive malignancies attributable to cigarette smoking, and could serve as a tool to monitor therapeutic outcomes in cancer patients.

This was presented at the 2008 Annual Meeting of the American Association for Cancer Research.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

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