The data remain mixed as to whether the genetic risk on chromosome 15 and lung cancer and COPD is related to heavier smoking (an indirect effect) or whether a direct biological mechanism increases lung cancer and COPD risk independent of smoking (a direct effect). Evidence in favor of a direct biological effect are that this genetic risk for lung cancer and COPD association with these variants remains after statistically accounting for duration of smoking history and number of cigarettes smoked per day (Lips et al., 2010). The α5 nicotinic receptor subunit is expressed in lung tissue, and a 30-fold up-regulation of expression of CHRNA5 is seen in lung cancer tissue compared to normal lung tissue (Falvella et al., 2009).
