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.
Written by Anna Sophia McKenney