1ATD carriers had a 70% increased risk of lung cancer, according to paper in Archives of Internal Medicine.

People with alpha1-antitrypsin deficiency (1ATD), a common genetic disorder in which the mutated genes were previously linked to lung disease, may have up to a 70% increased risk of lung cancer, according to researchers at Mayo Clinic, Rochester, MN.


Individuals with two copies of the associated genetic mutation often develop emphysema at an early age, according to previous research. Those with only one copy of the mutated gene do not normally have severe diseases related to 1ATD and may not be aware of their status, the investigators note. They may, however, be more vulnerable to cancer-causing tobacco smoke than noncarriers, the team reports.


The research team tested for 1ATD carrier status in 1,443 patients with lung cancer. In addition, 797 community members without lung cancer and 902 siblings of lung cancer patients were tested as controls. Information was gathered about all participants smoking history, demographic characteristics, and family history of cancer.


A total of 13.4% of the lung cancer patients and 7.8% of unrelated controls were 1ATD carriers. When patients with lung cancer were compared to these controls, 1ATD carriers had a 70% higher risk of developing lung cancer than noncarriers. Comparing patients with lung cancer to their cancer-free siblings, 1ATD carriers had twice the risk of developing lung cancer. The researchers estimated that 1ATD carrier status may account for 11% to 12% of patients with lung cancer enrolled in the study. Among those who had never smoked, 1ATD carrier status was associated with a 2.2-fold higher risk of lung cancer, with a 2-fold increased risk among light smokers and a 2.3-fold increased risk among moderate-to-heavy smokers.


Findings suggest that increased lung cancer risk among 1ATD carriers is independent of a family history of cancer, the investigators report. Patients with a family history of lung cancer or other cancers in their first-degree relatives had a similar 1ATD carrier rate to those without such a family history.


Results were published in the May 26 issue of Archives of Internal Medicine.

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