A common genetic disorder that has previously been linked to lung
disease may also put its carriers at a 70%-100% increased risk of lung
cancer, according to an article released on May 26, 2008 in the Archives
of Internal Medicine, one of the JAMA/Archives journals.
Alpha1-antitrypsin deficiency (α1ATD) is a among
the most common genetic conditions affecting the population of the
United States, especially the portion of European descent. The genetic
mutation, when inherited in both copies of the allele, often are
associated with the development of emphysema at a young age. Until now
carriers, who have only one copy of that mutated gene, have not been
linked to the same severe diseases of α1ATD
and are often unaware of their genetic situation. However, this study
indicates that they may be more sensitive to the carcinogens in tobacco
smoke than non-carriers are.
To investigate this, Ping Yang, M.D., Ph.D., and colleagues at the Mayo
Clinic, Rochester, Minn., examined 1,443 patients with lung cancer
for α1ATD. Additionally, 797 community
members who did not have lung cancer and 902 siblings of patients with
lung cancer were tested in a control population. All candidates were
questioned for smoking histories, demographic characteristsics, and
family history of cancer.
α1ATD carriers made up 13.4% of the lung cancer
patients and 7.8% of the unrelated controls. When compared to the
unrelated controls, patients with lung cancer had a 70% higher risk of
developing lung cancer when they had α1ATD. When
comparing lung cancer patients to the siblings without cancer, α1ATD
carriers had twice the chance of developing lung cancer. According to
the authors, α1ATD carriers could account to 11%
to 12% of the total patients with lung cancer who were enrolled in the
study.
Notably, in those who had never smoked, α1ATD
was linked to 2.2 times the risk of lung cancer. This increase was
2-fold in light smokers and 2.3fold in moderate to heavy smokers. The
authors indicate that this is independent of family history of cancer,
and only linked to carrier status: "Patients with a family history of
lung cancer or other cancers in their
first-degree relatives had a similar α1ATD
carrier rate to those
without such a family history, all significantly higher than the
controls," they write. "This finding suggests that increased
lung cancer risk among α1ATD carriers
is independent of a family
history of cancer."
The authors summarize that this gene is a promising jumping off point
for further understanding of the development of lung cancer: "In
summary, our findings demonstrate a paradigm in lung cancer etiology
research and risk assessment that incorporates clinical and genetic
markers for lung damage into a gene-environment interaction," they
conclude. "This knowledge may prove to be useful in further
understanding the pathologic mechanisms of lung cancer development and
in refining lung cancer risk assessment."
Alpha1-Antitrypsin Deficiency Carriers, Tobacco Smoke, Chronic
Obstructive Pulmonary Disease, and Lung Cancer Risk
Ping Yang, MD, PhD; Zhifu Sun, MD; Michael J. Krowka, MD;
Marie-Christine Aubry, MD; William R. Bamlet, MS; Jason A. Wampfler,
BS; Stephen N. Thibodeau, PhD; Jerry A. Katzmann, PhD; Mark S. Allen,
MD; David E. Midthun, MD; Randolph S. Marks, MD; Mariza de Andrade, PhD
Arch Intern Med. 2008;168(10):1097-1103.
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Anna Sophia McKenney