Precancer Markers Identified in Airway Epithelium Cells of Healthy Smokers

Newswise — SAN DIEGO — Smoking may be associated with the development of molecular features of cancer in the large airway epithelium. In the small airway epithelium, molecular cancerization is associated with development of chronic obstructive pulmonary disease, according to recent data. “We are striving to find the earliest molecular changes that are induced by environmental stressors — in this case, smoking,” said Renat Shaykhiev, M.D., Ph.D., assistant professor of genetic medicine at Weill Cornell Medical College, who presented the findings at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine, held Jan. 8-11, 2012. “Our goal is to understand the early pathogenesis of lung cancer and to develop strategies to prevent lung cancer in susceptible individuals.”

Shaykhiev and colleagues analyzed the large and small airway epithelia of healthy nonsmokers, healthy smokers and smokers with chronic obstructive pulmonary disease (COPD), which is typically caused by long-term smoking, for expression of so-called “molecular cancerization” features (i.e., the genes upregulated in lung cancer compared with nonmalignant adjacent tissue).

Researchers found significantly more cancer-like gene expression changes in the large airway epithelia of smokers than in those of nonsmokers. When analyzing the small airway epithelium, though, they did not find significant differences between healthy smokers and nonsmokers, but they did find significant overall upregulation of cancerization genes in smokers with COPD. Analysis of these genes in the large and small airway epithelia obtained from the same individuals revealed that molecular cancerization occurs more frequently in the large airway epithelium than in the small airway epithelium.

Shaykhiev and colleagues drew the following conclusions: Smoking is associated with acquisition of molecular cancerization features in the large airway epithelium prior to the development of disease, and the large airway epithelium is likely more susceptible to smoking-induced changes than the small airway epithelium, implying that it may be the primary site of molecular alterations leading to lung cancer in smokers.

These findings could potentially lead to the development of a diagnostic test that would look for these genetic changes in susceptible individuals, the researchers suggested.

“Ideally, we would use these genes to do very routine analysis to determine which smokers or even nonsmokers are at risk for development of lung cancer,” said Shaykhiev.

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About the AACR: The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The 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, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 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. The AACR publishes seven major peer-reviewed journals: Cancer Discovery; Cancer Research; Clinical Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Prevention Research. AACR journals received 20 percent of the total number of citations given to oncology journals in 2010. The AACR also publishes Cancer Today, a magazine for cancer patients, survivors and their caregivers which provides practical knowledge and new hope for cancer survivors. A major goal of the AACR is to educate the general public and policymakers about the value of cancer research in improving public health, the vital importance of increases in sustained funding for cancer research and biomedical science, and the need for national policies that foster innovation and the acceleration of progress against the 200 diseases we call cancer.

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About the IASLC:The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association’s membership includes more than 3,500 lung cancer specialists in 80 countries.

IASLC members promote the study of etiology, epidemiology, prevention, diagnosis, treatment and all other aspects of lung cancer and thoracic malignancies. IASLC disseminates information about lung cancer to scientists, members of the medical community and the public and uses all available means to eliminate lung cancer as a health threat for individual patients throughout the world. Membership is open to any physician, scientist, nurse or allied health professional interested in lung cancer, including patients, survivors, caregivers and advocates.

IASLC publishes the Journal of Thoracic Oncology, a valuable resource for medical specialists and scientists who focus on the detection, prevention, diagnosis and treatment of lung cancer.

To learn more about IASLC, visit http://iaslc.org