Sensitive to Smoke, Lung Cancer Gene

Medical Authors and Editors: Barbara K. Hecht, Ph.D. and Frederick Hecht, M.D.

July 27, 2004 -- A gene that determines the susceptibility to lung cancer has been localized to chromosome 6. This is the first major success in mapping the genetic vulnerability to lung cancer.

Lung cancer is a leading cause of death in the United States and many other countries. The risk is greatly increased by cigarette smoking and certain environmental exposures but genetic factors also clearly play a major role.

The Discovery

A report just posted online in the American Journal of Human Genetics outlines the discovery. A study was done of families with 3 or more first-degree relatives who had lung, throat, or laryngeal cancer with a special focus on those families that had affected relatives in at least 2 generations.

A battery of almost 400 genetic markers were examined in all available family members. The markers were DNA sequences known to be polymorphic, often variable.

The lung cancer susceptibility gene was found linked to a genetic marker on chromosome 6 with a high degree of certainty. The genetic marker is on the long (q) arm of chromosome 6.

And Now

The lung cancer region on 6q is quite large. It runs from chromosome band 6q23 through band 6q25. (Chromosome bands are so big that they can be seen under an ordinary microscope.) The region contains about 20 million base pairs, 20 million letters (A, T, G, or C) in the DNA.

To identify the gene itself responsible for lung cancer susceptibility is like looking for the proverbial needle in the haystack. However, this search may be sped up by first scrutinizing the most likely suspects, or candidate genes, Among them are several possible tumor suppressor genes known to be lurking in this region.

Ultrasensitive to Smoke

People carrying the familial lung cancer gene appear unusually sensitive to tobacco smoke Even a small amount of smoking may be enough to cause lung cancer. (By contrast, the risk of lung cancer rises with the amount of smoking in people who do not carry this gene.)

Comment

This is a major discovery. We expect that the gene will soon be identified and sequenced. That will end the first chapter in the book on the genetics of lung cancer susceptibility.

Source

JE Bailey-Wilson and others. A Major Lung Cancer Susceptibility Locus Maps to Chromosome 6q2325. Am. J. Hum. Genet., 75:000, 2004 (posted online)

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Related Links:

• Lung Cancer (article)
• Smoking and Quitting Smoking (article)
• Smoker's Lung: Pathology Photo Essay (article with interactive graphics)

Last Editorial Review: 7/27/2004