One explanation for the association of rs16969968 with lung disease independent of cigarette quantity is that the quantity of toxin inhaled when smoking is not well explained by the number of cigarettes smoked per day, suggesting that people with the risk allele of rs16969968 may inhale more deeply. To investigate this possibility, Le Marchand and colleagues48 conducted a study that evaluated the amount of nicotine and carcinogens consumed in a sample of 819 smokers. A positive association was found between the amount of nicotine metabolites seen in urine, a measure of the amount of nicotine consumed, and the minor variant of rs16969968 after adjusting for number of cigarettes smoked per day. This finding indicates that more nicotine and associated carcinogens are absorbed by individuals with the risk allele than individuals without the risk allele. Moreover, the differential absorption is not accounted for by number of cigarettes smoked per day. Because these data argue that number of cigarettes smoked per day is not a complete proxy for nicotine and toxin absorption, the association between lung cancer and rs16969968 may still be
