To estimate the extent to which the association of rs1051730–rs16969968 genotype with lung cancer is mediated via smoking, we applied the effect size we observed for the association with cotinine levels to published data on the association between cotinine levels and lung cancer risk. Applying weighted least squares regression to the log odds ratios presented by Boffetta et al. (46) produced a regression coefficient of 0.001945 per nmol/L of serum cotinine for the association between cotinine levels and lung cancer risk (Supplementary Figure 1, available online). Thus, the observed per-allele increase in cotinine levels of 138.72 nmol/L (95% CI = 97.91 to 179.53) would indicate an increased risk of lung cancer with each additional copy of the rs1051730–rs16969968 risk allele (per-allele OR = 1.31, 95% CI = 1.21 to 1.42). This corresponds closely with published data for the association between rs1051730–rs16969968 genotype and lung cancer risk, where an odds ratio of 1.32 has been reported (1).
