TY - JOUR T1 - Translating genomics into risk prediction JF - Thorax JO - Thorax DO - 10.1136/thoraxjnl-2016-209934 SP - thoraxjnl-2016-209934 AU - Emily S Wan AU - Dawn L DeMeo Y1 - 2017/03/20 UR - http://thorax.bmj.com/content/early/2017/03/20/thoraxjnl-2016-209934.abstract N2 - Cigarette smoking is a leading risk factor in the development of cardiovascular, pulmonary and malignant diseases worldwide.1 Yet, it remains one of the most challenging environmental exposures to quantify. Rudimentary categorisations of ‘never’, ‘former’ and ‘current’ smoker capture only a fraction of the complexity associated with the exposure. Attempts to quantify cumulative cigarette smoke exposure, for example by calculating ‘pack-years’, are notoriously imprecise, partially because of a failure to account for variations in behaviour such as (1) depth of inhalations, retention time before exhalation and timing between puffs, (2) intermittent periods of abstinence or relapse, and (3) a reliance on self-reported recall of smoking habits over extended periods of time (often years to decades). Additionally, biological differences related to age, gender, body size, and variations in absorption and metabolism among smokers further complicate our attempts to quantify the ‘effective exposure’ to cigarette smoke for any given individual.Given these complexities, the use of biomarkers, both qualitative and quantitative, as an objective measurement of ‘effective exposure’ is conceptually appealing. To date, the most widely used smoking biomarkers are cotinine and carbon monoxide (CO). Measurement of CO, either in exhaled breath or in blood as carboxyhaemoglobin, has been shown to correlate with smoking intensity, however the relatively short half-life of CO (t1/2 1–6 hours) limits its utility to assessments of recent smoking behaviours.2 Cotinine, a direct metabolite of nicotine which is measurable in the blood, urine and tissues is another well validated biomarker of cigarette smoke exposure. The slightly longer half-life (t1/2 16–20 hours), as well as the assessment of cotinine in slower growing tissues such as hair and nail clippings, extends the potential period of monitoring for this assay to the order of weeks to months. … ER -