There are some limitations to consider when interpreting these results. First, our data are drawn from disparate studies recruited from various populations. Nevertheless, the consistency in effect size estimates across samples, and the lack of substantial between-study heterogeneity, suggests that the impact of this is minimal. Second, our estimate of the strength of the association between genotype and cotinine exposure on lung cancer risk relies on an indirect comparison with published data. Moreover, it relies on measures of current smoking rather than lifetime exposure, which is more strongly associated with lung cancer risk. Nevertheless, the triangulation of our data with published estimates of the association of genotype with lung cancer risk raises confidence in these results. Third, we lacked repeated measurement of cotinine, which would allow the assessment of within- and between-person variation (eg, due time between last cigarette smoked and collection of biological sample for cotinine analysis), and the time of day that cotinine samples were collected was not standardized, either within or between samples. However, the relatively long half-life of cotinine means it provides a reasonably stable measure
