Alpha1-antitrypsin deficiency allele carriers among lung cancer patients

Ping Yang, Kimberly A. Wentzlaff, Jerry A. Katzmann, Randolph S. Marks, Mark S. Allen, Timothy G. Lesnick, Noralane M. Lindor, Jeffrey L. Myers, Elaine Wiegert, David E. Midthun, Stephen N. Thibodeau, Michael J. Krowka

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


Lung cancer (LC) and chronic obstructive pulmonary lung diseases (COPDs; including emphysema and chronic bronchitis) share a common etiology. Despite the known associations of alpha1-antitrypsin deficiency (α1AD) with COPD and COPD with LC, few studies examined the association of α1AD alleles and LC. We hypothesize that heterozygous individuals who carry a deficient allele of the α1AD gene Pi (protease inhibitor locus) are at an increased risk of developing LC. The Pi locus is highly polymorphic with >70 variants reported. There are at least 10 alleles associated with deficiency in alpha1- antitrypsin. Using an exact binomial test, we compared the α1AD carrier rate in 260 newly diagnosed Mayo Clinic LC patients to the reported carrier rate in Caucasians in the United States (7%). α1AD carrier status, determined by isoelectric focusing assay, was examined with respect to the history of cigarette smoking, COPD, and histological types. Thirty-two of the 260 patients (12.3%; 95% confidence interval, 8.6-16.9%) carried an α1AD allele, which was significantly higher than expected (P = 0.002). Twenty- four of the 32 carriers had allele S, 6 had allele Z, and 2 had allele I. Patients who never smoked cigarettes were three times more likely to carry a deficient allele (20.6%; P = 0.008), although smokers had a higher carrier rate (11.1%; P = 0.025) when compared with the 7% rate. Patients with squamous cell or bronchoalveolar carcinoma had a significantly higher carrier rate than expected (15.9% and 23.8%, P ≤ 0.01, respectively). Our preliminary findings suggest that individuals who carry an α1AD allele may have an increased risk for developing LC, specifically squamous cell or bronchoalveolar carcinoma.

Original languageEnglish (US)
Pages (from-to)461-465
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Issue number5
StatePublished - May 1999

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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