Modelling the Complex Smoking Exposure History in Assessment of Pan-Cancer Risk

Modelling complex smoking histories, with more comprehensive and flexible methods, to show what profile of smoking behavior is associated with the risk of different cancers remains poorly understood. This study aims to provide insight into the association between complex smoking exposure history and pan-cancer risk by modelling both smoking intensity and duration in a large-scale prospective cohort. Here, we used data including a total of 0.5 million with cancer incidences of 12 smoking-related cancers. To jointly interpret the effects of intensity and duration of smoking, we modelled excess relative risks (ERRs)/pack-year isolating the intensity effects for fixed total pack-years, thus enabling the smoking risk comparison for total exposure delivered at low intensity (for long duration) and at a high intensity (for short duration). The pattern observed from the ERR model indicated that for a fixed number of pack-years, low intensity/long duration or high intensity/short duration is associated with a different greater increase in cancer risk. Those findings were extended to an increase of time since smoking cessation (TSC) showing a reduction of ERR/pack-year for most cancers. Moreover, individuals with favorable lifestyle behaviors, such as regular physical activity and healthy dietary intakes, were shown to have lower ERRs/pack-year, compared to those with unfavorable lifestyle behaviors. Overall, this study systematically evaluates and demonstrates that for pan-cancer risks, smoking patterns are varied, while reducing exposure history to a single metric such as pack-years was too restrictive. Therefore, cancer screening guidelines should consider detailed smoking patterns, including intensity, duration, and cessation, for more precise prevention strategies. Highlights (Key context and significance)O_LIDistinct cancer risk patterns emerge based on smoking exposure beyond equal pack-years: smoking duration is a stronger risk factor for some cancers, while smoking intensity dominates for others. C_LIO_LITime since smoking cessation (TSC) significantly lowers cancer risk: former smokers experience substantial reductions in risk for most cancers within the first 20 years after quitting. C_LIO_LIFavorable lifestyle behaviors mitigate cancer risks: individuals with regular physical activity and healthy diets show lower excess relative risks (ERRs) for most cancers, compared to those with unhealthy habits. C_LIO_LITailored cancer screening based on smoking behavior: cancer screening guidelines should consider detailed smoking patterns, including intensity, duration, and cessation, for more precise prevention strategies. C_LI