Toenail nicotine level as a novel biomarker for lung cancer risk.

The objective of this US study was to assess the association of toenail nicotine level as a novel biomarker with lung cancer risk independent of reported smoking history. A nested case-control study of 210 male lung cancer cases and 630 matched controls aged 40-75 years participating in the Health Professionals Follow-up Study was conducted. Toenail samples collected in 1987 were analyzed for nicotine levels, and incident lung cancer cases were diagnosed between 1988 and 2000. Mean toenail nicotine level among cases was 0.95 ng/mg compared with 0.25 ng/mg among controls (P < 0.0001). In univariate analyses, the relative risk of lung cancer for the highest versus lowest quintiles of toenail nicotine level was 10.50 (95% confidence interval: 5.61, 19.64; P for trend < 0.0001). When the authors adjusted for pack-years from reported smoking history in multivariate analyses, the relative risk for toenail nicotine levels in the highest quintile was still significant in predicting lung cancer risk: 3.57 (95% confidence interval: 1.73, 7.37; P for trend < 0.0001). In conclusion, the toenail nicotine biomarker was found to be a strong predictor of lung cancer independent of smoking history, suggesting that the adverse effects of cigarette smoke may be underestimated in studies based on smoking history only.