However, some studies have suggested a direct link between CHRNA5-CHRNA3-CHRNB4 variants and lung cancer: The risk of lung cancer that can be attributed to the CHRNA5-CHRNA3-CHRNB4 variants is higher than can be explained by the variant’s effect on smoking quantity (123), and the genetic risk for lung cancer and COPD remains after the risk associated with smoking has been statistically accounted for using CPD and the duration of smoking (86). Other studies, however, have shown that the amount of nicotine absorbed by smokers is not fully accounted for by CPD owing to differences in how individuals smoke (56, 60).
