GWAS approaches have revealed that several SNPs within the nAChR gene cluster are significantly associated with the risk of lung cancer and COPD (5, 68, 118, 123). The most strongly associated SNPs are the same as those that show association with nicotine dependence and CPD in other studies (13, 112, 123, 124a). It is unclear whether the association of this locus with lung cancer is a direct biological effect on lung cancer susceptibility or is mediated through effects on increased risk of smoking. Although SNPs at this locus are only weakly associated with lung cancer risk in those who have never smoked, they are associated with risk for other smoking-associated cancers and diseases (86, 126). This implies that this locus predisposes individuals to increased tobacco consumption, leading to increased risk for cancer.
