Analysis of a missense SNP in the aryl hydrocarbon receptor repressor gene that may disproportionately increase lung cancer risk in Black Americans

The parent grant studies a single nucleotide polymorphism (SNP) in the aryl hydrocarbon receptor repressor (AHRR) gene that may influence the lung cancer risk of Black/African American (B/AA) subjects. AHRR is a negative regulator of detoxification responses involved in the metabolism and elimination of tobacco smoke

carcinogens. B/AA men have the highest rate of lung cancer death compared to all other groups, with a 12% higher lung cancer incidence rate and a 15% higher lung cancer death rate than White/European (W/E) men. Elevated AHRR expression has been implicated in lung cancer risk; thus, a SNP that improves AHRR function

would likely increase lung cancer risk. We have identified a missense SNP, rs35008248, in AHRR exon 4 that, while rare in W/E subjects, is present one third of B/AA subjects. The SNP was not included in most previously used arrays. Preliminary data from GWAS explorer suggests an association with smoking in B/AA males

(p=3.87E-3) and with smoking-related cancers in B/AA subjects (p=0.04927). B/AA individuals comprise only a small fraction of the subjects (