Scientists have found evidence in all major types of lung cancer of a genetic defect that suggests the disease may appear after a protective gene is lost.
In a study of 38 lung cancer patients, the absence of the gene appeared so consistently that it must be important in development of the disease, but scientists will have to isolate the gene before they can determine its role, said researcher Ben Carritt.
The finding, published today in Nature magazine, indicates that the defect is "widespread if not universal in lung cancer," said Carritt, of the Medical Research Council's Human Biochemical Genetics Unit at University College in London.
While the work has no immediate application in prevention or therapy, any insights into how cancers arise may pay off for devising treatments in the future for the nation's leading cancer killer, he said.
136,000 Deaths Yearly
Lung cancer kills about 136,000 Americans each year. Scientists had previously found evidence of the gene loss in small-cell lung cancer, which accounts for about 25% of the nation's annual 150,000 lung cancer cases.
Carritt said the new findings support the idea that lung cancer can appear after an "anti-oncogene" stops working in a lung cell. Such genes are in a sense the opposite of oncogenes, which cause cancer.
The normal role of the anti-oncogene may be to shut off other genes that make the lung cell grow and divide at the proper times, Carritt said. If the anti-oncogene is disabled through mutation or lost, the cell could proceed to unregulated, cancerous growth, he said.
The mutation or loss could be caused by smoking, said Carritt, who said his study does not imply any inherited susceptibility to lung cancer.
Evidence for anti-oncogenes has been found in several other cancers, including colon-rectum cancer.
Each cell gets two copies of most genes by inheriting pairs of chemical threads called chromosomes, on which genes reside.
Researchers looked for evidence that a particular portion of one of the two copies of chromosome 3 had been deleted in lung tumor cells. If one copy of the anti-oncogene was already damaged by mutation, the deletion could remove the remaining normal copy, opening the door to cancer.
All seven small-cell lung cancer patients showed a deletion, researchers reported. For squamous cell lung cancer, which accounts for one-fourth of lung cancer cases, evidence suggesting deletion appeared for 16 patients and was corroborated in the cells of two patients tested with a different research procedure.
And for adenocarcinoma, which accounts for about 30% of lung cancer cases, evidence of deletion was found in 14 patients and corroborated in five. A single available case of large-cell carcinoma, which accounts for perhaps 15% of all lung cancer cases, also showed evidence of deletion.