In conclusion, the present study confirms previous associations of SNPs on 15q25 with cotinine levels. The study also indicates that circulating cotinine levels may provide more refined information on recent smoking exposure than does CPD as assessed by questionnaires. The intriguing associations of SNPs on 19q13 with cotinine levels, opposite to that of CPD and lung cancer risk, should be studied further by measuring additional nicotine metabolites. Finally, the present study indicates that the degree to which the established effects of 15q25 SNPs on lung cancer risk are mediated by smoking may be under-estimated by use of crude measures of smoking such as CPD. Further studies with a range of objective smoking measures covering a greater period of lifetime smoking are required to further elucidate this issue.