Location of Potential Familial Lung Cancer Gene Discovered
Researchers have discovered 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), both part of the National Institutes of Health (NIH), identified
a major lung cancer susceptibility region on a segment of chromosome
6. The findings appear in a just-posted-online edition of American
Journal of Human Genetics* and will appear in print in the September
The Genetic Epidemiology of Lung Cancer Consortium (GELCC)** examined
52 families who had at least three first-degree family members affected
by lung, throat, or laryngeal cancer. Of these 52 families, 36 had
affected members in at least two 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 (the different variations each gene can take) of all
affected and non-affected family members who were willing to participate
in the study.
The researchers found strong evidence that a lung cancer susceptibility
gene or genes is 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 locus was a critical first step,
but more work needs to be done.
"The genetic markers are like those mileage markers you see
on the side of the highway," explained NCI's Jonathon Wiest,
Ph.D. "They can be very useful for broad navigational purposes,
but at the same time they don't give you precise information about
all the interesting things that may lie along the highway."
The next goal for these researchers is to more closely examine this
region of chromosome 6 with the aim of locating the exact gene or
genes that cause lung cancer susceptibility. The identified region
corresponds to roughly a 20 million base pair segment on the long
arm of chromosome 6. The region contains numerous genes that are
likely candidates for the susceptibility gene, including four suspected
tumor suppressor genes. However, Wiest pointed out that "often
you can discover a new function for a gene that normally works in
a different cellular pathway, so you never know what you're going
Another interesting discovery the team made involved the effects
of smoking on cancer risk for carriers and non-carriers of the predicted
familial lung cancer gene. They found that in non-carriers, the
more they smoked, the greater their risk of cancer. In carriers,
on the other hand, 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.
The researchers also plan to continue screening additional families
who could have familial lung cancer, to confirm this particular
susceptibility region, and perhaps find additional regions. "The
discovery of genes for other types of cancer has led to better understanding
of those diseases, which in turn can lead to better strategies for
treatment and prevention. We hope that uncovering a gene or genes
responsible for lung cancer will do the same for this devastating
disease," said co-lead author Joan Bailey-Wilson, Ph.D., NHGRI.
Lung cancer is by far the leading cause of cancer death in the United
States (over 160,000 deaths expected in 2004), and the five-year
survival rate is only 15 percent. Such a high mortality, combined
with the large amount of spontaneous lung cancers that arise from
smoking, makes finding potential histories of familial lung cancer
or collecting genetic samples extremely difficult and time consuming.
"This study is just further proof of the importance of cooperative
efforts and large-scale science in genetic epidemiology research,"
said Daniela Seminara, Ph.D., NCI.
NHGRI and NCI are two of the 27 institutes and centers at NIH,
an agency of the Department of Health and Human Services.
For more information about cancer, visit the NCI Web site at
http://www.cancer.gov or call
NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Additional information about NHGRI can be found at its Web site,
* Bailey-Wilson JE, Amos CI, Pinney SM, Petersen
GM, de Andrade M, Wiest JS, Fain P, Schwartz AG, You M, Franklin W,
Klein C, Gazdar A, Rothschild H, Mandal D, Coons T, Slusser J, Lee
J, Gaba C, Kupert E, Perez A, Zhou X, Zeng D, Liu Q, Zhang Q, Seminara
D, Minna J, Anderson M. A major lung cancer susceptibility locus maps
to chromosome 6q23-25. American Journal of Human Genetics,
** The Genetic Epidemiology of Lung Cancer Consortium (GELCC) includes
Jonathon Wiest, Ph.D., and Daniela Seminara, Ph.D., both of NCI;
Joan Bailey-Wilson, Ph.D., of NHGRI; Christopher Amos, Ph.D., of
M.D. Anderson Cancer Center; Gloria Petersen, Ph.D., and Mariza
de Andrade, Ph.D., of the Mayo Clinic; Susan M. Pinney, Ph.D., of
the University of Cincinnati; Pamela Fain, Ph.D., of the University
of Colorado Health Sciences Center at Denver; Ann Schwartz, Ph.D.,
of Karmanos Cancer Institute; Ming You, M.D., Ph.D., of Washington
University (St. Louis); Adi Gazdar, M.D., and John Minna, M.D.,
of University of Texas Southwestern Medical Center; Henry Rothschild,
M.D., of Louisiana State University Health Sciences Center at Dallas;
and Teresa Coons, Ph.D., of the Saccomanno Research Institute. The
GELCC is headed by Marshall Anderson, Ph.D., of the University of