Exposing lung cancer as a genetic disease.
While lung cancer is not considered an overtly inherited disease, recent studies suggest that genetics may determine whether an individual develops the disease, scientists said last week. Going beyond studies of carcinogen exposure, researchers are trying to redefine the causes of lung cancer on the basis of a complex assortment of genes that either promote or prevent the disease.
Much of the recent lung cancer work stems from an upsurge of interest in tumor suppressor genes. Along with evidence that genetics plays a causative role in many cancers came the idea that the body has so-called tumor suppressor genes responsible for keeping cancer-related genes under control. When suppressor genes are lost through mutation, however, the cancer genes (oncogenes) are free to do their grim deed, say scientists who have been sifting through various cancers seeking tumor suppressor genes. The search, at least at least in th case of lung cancer, also embraces the relatively new study of self-promoting growth factors made by cells themselves, as well as the concept of multiple deletions.
According to John D. Minna of the Bethesda, Md-based National Cancer Institute (NCI), new data suggest that an absence of tumor suppressor genes may lead to lung cancer. (Scientists already suspect the oncogenes myc and ras have a role in the disease.) While Minna says cigarette smoking can cause a loss of tumor suppressor genes and other genetics changes that lead to lung cancer, he feels heredity is partly resposible for a predisposition to the disease. He reported NCI's latest results last week in New Orleans at the American Association for Cancer research's meeting.
Minna and his co-workers are looking for suppressor genes in a region on chromosome 3 that is "nearly always" missing in cells taken from small-cell lung cancer patients, and is sometimes deleted from other types of lung cancers. Among the 33 cases of small-cell lung cancer studied thus far, NCI scientists have found the abnormality in 31 samples. They also have found deletions on several other chromosomes.
Because each normal cell has two copies of chromosome 3, for example, Minna says there must be a double loss of suppressor genes at some time before lung cancer growth begins. It is likely the losses take place at two different times during years of cigarette smoking or exposure to radon or other chemicals, Minna says, and perhaps one deletion may be inherited from a parent, making a person more susceptible to smoking-caused lung cancer. For example, after statistics are corrected for smoking habits, close relatives of lung cancer patients still have a three-fold risk of developing the disease, he notes.
Genetic damage accelerates, Minna suggests, because normal lung cells apparently produce their own growth factors. This prompts duplication of cells with the initial deletion, thus providing even more targets for the critical second deletion. Included among these growth factors, which are also produced by cancer cells, are insulin-like growth factors and gastrin-releasing peptide.
Looking at the evidence gathered thus far, Minna says "lung [cells] may actually be the repository of virtually all of the chromosome deletions [caused by factors like environment exposures]." He says this "accumulation" phenomenon, with its multiple genetic damage, may be responsible for recent observations made during an ongoing NCI study -- in which half of the patients cured of small-cell lung cancer later developed other types of cancer.
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|Date:||Jun 4, 1988|
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