The effects of these loci on lung cancer risk might be mediated by their effect on smoking behavior. However, in the case of the 15q25 locus, adjusting for self-reported smoking (smoking status, pack years, CPD) only partially attenuates the risk effect(18,19) and the remaining ~30% increase in risk observed per risk allele appears to be in excess of that expected from the increase in CPD conferred by the missense variant. Nevertheless, as CPD is a crude measure of how 15q25 variants influence propensity to smoke, additional aspects of smoking such as differences in inhalation may explain this association. Using cotinine measurements together with self-reported information might increase the reliability of smoking exposure data and allow for a more thorough (although by no means complete) adjustment for recent smoking behavior.
