There is also evidence that the genetic effect for this region and lung cancer and smoking may be only through the genetic effects of smoking. The association of the chromosome 15 region and lung cancer is not seen in non-smokers [18]. Secondly, though cigarettes smoked per day is a reasonable proxy for exposure, it does not fully capture the carcinogenic and toxic exposure risk associated with smoking. For example, among smokers who report smoking the same number of cigarettes per day, the quantity of toxin and carcinogen exposure varies, and individuals who have this risk variant rs16969968 appear to ingest more toxins, which is likely due to more intensive smoking such as inhaling more deeply and frequently while smoking [25]. Because the vast majority lung cancer and COPD cases are attributable to smoking, and carcinogenic exposure varies between smokers even when smoking the same number of cigarettes per day, it is unlikely that further statistical tests will be able to dissect whether this genetic association with smoking-related diseases is acting only through smoking genetic risk or whether there remains an
