EPIDEMIOLOGY AND SUSCEPTIBILITY IN LUNG CANCER

Eighty-five percent of lung cancers are caused by tobacco
smoke, where exposure to carcinogens present in tobacco
smoke leads to the acquisition of genetic mutations that may
eventually initiate carcinogenesis. However, not all lung cancers
arise in smokers, and not all smokers will develop lung cancer.
Thus, inherited factors must be involved that may predispose
an individual to develop lung cancer—either by increasing
susceptibility to the damaging effects of carcinogen exposure
or by increasing susceptibility regardless of smoking history.
Worldwide, approximately 25% of lung cancer cases are not
attributable to smoking. 4 These cases occur more frequently in
women, especially in Asian countries, target the distal airways,
and are commonly adenocarcinomas. Coupled with molecular
data that indicates strikingly different mutation patterns
between known lung cancer genes such as KRAS , epidermal
growth factor receptor (EGFR) , and TP53 and clinical data in
relation to response to targeted therapies, it has now been suggested
that lung cancer in never-smokers be considered a distinct
disease from the more common tobacco smoke–related
lung cancer. 4
Many studies have examined the effect of single nucleotide
polymorphisms (SNPs) on the risk of developing lung
cancer. 5,6 The reported risk effect in these studies is generally
modest and often inconsistent, explaining why none are in routine
use. However, metaanalyses as well as use of whole-genome
SNP microarrays may hold the key to identifying robust and
possible synergistic interactions between the modest affect of
multiple SNPs. Lung cancer risk was recently associated with
genomic variation at 15q24/q25.1 by three separate studies
simultaneously that used whole-genome SNP microarrays. 7–9
Although the conclusions of the three studies differed in whether
the risk is conferred directly with cancer or through nicotine
addiction, the genes within this locus—which include several
genes encoding nicotinic acetylcholine receptor subunits—
represent important targets for further functional analyses.