| Peripheral
lung adenocarcinoma, and bronchioalveolar carcinoma
(BAC) in particular, continues to account for
the majority of lung cancers in young (<55),
non-smoking, women. BAC patients constitute about
5% of the total lung cancer patients in the U.S.
Lung cancer overall is now responsible for more
cancer-related deaths than any other cancer, killing
more women in the United States each year than
breast and ovarian cancers combined.
Much of the success of modern cancer molecular
genetics centres around the discovery of cancer
susceptibility genes with mendelian inheritance
patterns. Many of these individual susceptibility
alleles are rare, however, and account for a small
minority of the inherited component of cancer.
No such genes have been identified with an association
to any form of lung cancer. Current thinking suggests
that the large majority of human cancers, particularly
solid tumors such as lung cancer, are the result
of tens or hundreds of susceptibility alleles
that in combination underlie the genetic component
of disease.
The rapid acquisition of data on common single-nucleotide
polymorphisms (SNPs) as an offshoot of human genome
sequencing projects has made it possible to test
for the association of candidate genes or regions
with disease. A refinement of this data from the
recent publication of the HapMap project results
(www.hapmap.org) in combination with cheaper genotyping
technologies has made whole-genome studies a feasible
prospect. We propose to use high-throughput technology
to perform whole-genome genotyping of 550,000
tagSNP markers derived from the HapMap project
on patient samples from a cohort of 80 patients
with bronchioalveolar carcinoma and 40 matched
controls. Patient samples will be identified from
the Mayo Clinic Lung Tumor Bank following informed
consent, and genomic DNA purified from frozen
blood samples. This whole genome survey will analyse
the majority of validated SNPs within the human
genome in an attempt to find genetic abnormalities
associated with the development of BAC. SNP associations
with disease susceptibility from this project
will provide lead data toward the project goal
of defining the underlying genetic basis for the
development of BAC.
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