Project: Research project

Project Details


DESCRIPTION (Adapted from the Applicant's Abstract): Lung cancer provides an
ideal paradigm for investigating gene-environmental interactions. Although a
majority of lung cancer victims are tobacco users, the unresolved paradox is
that only a minority of long-term heavy smokers will develop the disease.
Therefore, genetically determined susceptibility is likely an important
component in lung cancer development. We plan to examine the role of the
alpha1AD gene in lung cancer risk. This is a logical step because individuals
who are either homozygous or heterozygous (carriers) for the alpha1AD allele
are predisposed to the development of chronic obstructive pulmonary disease
(COPD). COPD is a risk factor for lung cancer and shares common risk factors
with lung cancer, such as cigarette smoking and familial aggregation. Thus, we
hypothesize that alpha1AD allele carriers have an increased risk for lung
cancer. The proposed case-control study is designed to test this hypothesis. As
secondary hypotheses, we will test whether the association between lung cancer
risk and alpha1AD carrier status varies by history of tobacco smoke exposure,
COPD, histopathologic type of the tumor, and family history of cancer. Twelve
hundred cases with primary lung cancer who are newly diagnosed (from April 1997
to September 2001) at Mayo Clinic will be recruited as the case group. Twelve
hundred population-based controls (matched by age, gender, and race) will be
assembled for testing the hypothesis that alpha1 AD carriers are at a higher
lung cancer risk. Approximately twelve hundred full siblings from 600 lung
cancer cases will be included as an ethnicity-matched control group to
eliminate the bias due to population admixture (as observed in our pilot
study). Data will be collected from medical records, patient interview, and
self-administered questionnaires. Alpha1-antitrypsin (a protease inhibitor, Pi)
allele type will be determined by isoelectric focusing assay. Statistical
analyses include multiple logistic regression models for case-population
control comparisons and a newly developed multivariate score statistic will be
used for case-sibling control comparisons.

This study will allow us to evaluate the roles of 1) a common gene that is
associated with lung tissue damage, 2) tobacco smoke (carcinogen) exposure, and
3) COPD that shares common risk factors with lung cancer and often occurs
before the onset of lung cancer. Results from this study will lead to further
understanding of the biologic basis of lung cancer development and progression,
may uncover an additional marker for identifying high-risk individuals, and
could provide additional impetus for targeted behavior modification,
chemo-prevention, and gene therapy programs.
Effective start/end date3/10/009/29/11


  • National Cancer Institute: $499,786.00
  • National Cancer Institute: $451,218.00
  • National Cancer Institute: $503,405.00
  • National Cancer Institute: $311,284.00
  • National Cancer Institute: $99,602.00
  • National Cancer Institute: $523,787.00
  • National Cancer Institute: $524,374.00
  • National Cancer Institute: $524,983.00
  • National Cancer Institute: $466,357.00


  • Medicine(all)


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