Researchers have found a possible inherited component for lung cancer, a disease normally associated with external causes, such as cigarette smoking. An interdisciplinary consortium consisting of 12 research institutions and universities, including the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), identified a major lung cancer susceptibility region on a segment of chromosome 6. The findings appear in the online edition of American Journal of Human Genetics and will appear in print in the September 2004 issue.

The Genetic Epidemiology of Lung Cancer Consortium examined 52 families who had at least 3 first-degree family members affected by lung, throat, or laryngeal cancer. Of these 52 families, 23 had 5 or more affected members in at least 2 generations. Using 392 known genetic markers, which are DNA sequences that are known to be common sites of genetic variation, the researchers generated and then compared the alleles of all affected and nonaffected family members who were willing to participate in the study.

The research consortium is led by Dr. Marshall Anderson of the University of Cincinnati and includes Dr. Jonathan Wiest of NCI and Dr. Joan Bailey-Wilson of NHGRI, as well as many other researchers from eight other institutions around the country. They found strong evidence that a lung cancer susceptibility gene or genes are co-inherited with a genetic marker on chromosome 6. Markers on chromosomes 12, 14, and 20 also indicated possible linkage to lung cancer susceptibility, although the results were not as strong. Identifying the location was a critical first step, but more work needs to be done.

"The genetic markers are like the mileage markers you see on the side of the highway," explained Dr. Wiest. "They can be very useful for broad navigational purposes, but they don't give you precise information about all the interesting things that may lie along the highway."

Another discovery the team made involved the effects of smoking on cancer risk for carriers and noncarriers of the gene. They found that in noncarriers, the more they smoked, the greater their risk of cancer. In carriers, however, any amount of smoking increased lung cancer risk. These findings suggest that smoking even a small amount can lead to cancer for individuals with inherited susceptibility.

"Smoking remains the most critical risk factor for lung cancer," said Dr. Wiest. "Identification of the gene may one day enable us to screen for individuals at high risk for lung cancer, but this does not mean that smoking is safe or that individuals without this gene are protected in any way, particularly if they smoke."

"The discovery of genes for other types of cancer has led to better understanding of those diseases, which in turn can lead to better treatment and prevention. We hope that uncovering a gene or genes responsible for lung cancer will do the same for this devastating disease," said Dr. Bailey-Wilson.

The next goal for these researchers is to pinpoint the exact gene or genes within the region responsible for the susceptibility. They also plan to continue screening additional families that could have familial lung cancer, both to confirm their findings and find additional susceptibility regions.