Associations have been found between lung cancer and an SNP in LD with rs16969968, rs1051730.33,34,45,46 Various methodologies have been used to try to separate the environmental contribution of nicotine dependence from a direct genetic contribution to lung cancer of rs1051730 or a related SNP. Several researchers found increased risk for lung cancer after adjusting for smoking, supporting the hypothesis that rs1051730 contributes to lung cancer independent of nicotine dependence. 33,45,46 Amos and colleagues46 found an association between lung cancer and rs1051730 in 3 independent samples, robust to adjustment for pack-years of cigarette exposure. However, the association between rs1051730 and lung cancer was absent in nonsmokers. If rs1051730 were related to lung cancer independent of smoking exposure the effect would be present in nonsmokers. Despite this, the repeated evidence of association of this variant with lung cancer independent of degree of smoking exposure among those who have smoked argues that there is an association between rs1051730 (and related SNPs) and lung cancer beyond the impact on risk of nicotine dependence itself.
