Recently genome-wide association (GWA) studies of lung cancer have shown common variation at 15q24−25.1 as a determinant of risk(1–3). Two studies found that the same alleles at this locus increased risk of lung cancer and influenced tobacco smoking behaviour. Genes mapping to this region of association include CHRNA3, CHRNA4, CHRNA5, PSM4, LOC123688, and IREB2. The CHRNA genes encode the nicotinic receptor subunits; in addition to playing a role in development of nicotine dependence, nicotine receptors also influence cell proliferation and apoptosis. Hence these genes represent strong candidates for combined lung cancer susceptibility and predilection to smoking. PSMA4 encodes the fourth component of the proteasome which plays a role in protein degradation and IREB2 is involved in iron metabolism which may thus impact on oxidative damage. A second lung cancer locus identified through the GWA studies maps to 5p and includes the genes encoding TERT and CLMPTL1. In addition to these loci we and others have found statistically significant evidence implicating a third locus at 6p as a risk factor for lung cancer(4, 5).
