Gene Methylation Determination May Help Stratify Smokers’ Cancer Risk

NEW YORK (Reuters Health) - Aberrant methylation of genes in the upper aerodigestive tract of heavy smokers may be a marker of high lung cancer risk, researchers report in the November issue of the International Journal of Cancer.

As lead investigator Dr. Sabine Zochbauer-Muller told Reuters Health, “aberrant methylation of the promoter region of certain tumor suppressor genes leads to gene silencing and is frequently detected in lung tumors. However, aberrant methylation of certain genes can already be detected in the bronchial epithelium from heavy smokers.”

In their investigation, Dr. Zochbauer-Muller of University Hospital, Vienna, Austria and colleagues studied sputum, bronchoalveolar lavage and other specimens from the upper aerodigestive tract epithelium of heavy smokers. None of these subjects had evidence of cancer, but they did show morphometric evidence of sputum atypia. Also examined were sputum samples from 30 subjects who had never smoked.

At least one gene from one or more samples from 48% of the smokers showed aberrant methylation. In 17% of smokers, 2 or more genes were methylated.

Methylation was significantly less common in never smokers and, overall, was seen more frequently in samples from the central airways than the peripheral airways or the oropharynx. RAR beta-2 was the gene most often involved.

The data, Dr. Zochbauer-Muller continued, “suggest that detection of aberrant methylation could be used in a population with increased risk for getting lung cancer to assess the ‘individual’ risk. Determining the methylation status of several genes and performing a ‘methylation profile’ could allow the identification of individuals with a very high lung cancer risk.”

This high-risk subgroup of people, she concluded “could then undergo other, but more costly, procedures for early detection of lung cancer such as spiral CT scan. They would also be ideal candidates for chemoprevention trials.”

Source: Int J Cancer 2003;107:612-616. [ Google search on this article ]

MeSH Headings:Alkylation: Biological Sciences: Biology: Chemistry: Chemistry, Organic: Gene Expression Regulation: Genetics: Genetics, Biochemical: Lung Neoplasms: Methylation: Molecular Biology: Neoplasms: Neoplasms by Site: Physical Sciences: Respiratory Tract Neoplasms: Smoking: Thoracic Neoplasms: DNA Methylation: Gene Silencing: Biological Sciences: Diseases: Physical SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.

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