Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium

José Manuel Ordóñez-Mena, Ben Schöttker, Ute Mons, Mazda Jenab, Heinz Freisling, Bas Bueno-de-Mesquita, Mark G. O’Doherty, Angela Scott, Frank Kee, Bruno H. Stricker, Albert Hofman, Catherine E. de Keyser, Rikje Ruiter, Stefan Söderberg, Pekka Jousilahti, Kari Kuulasmaa, Neal D. Freedman, Tom Wilsgaard, Lisette CPGM de Groot, Ellen Kampman, Niclas Håkansson, Nicola Orsini, Alicja Wolk, Lena Maria Nilsson, Anne Tjønneland, Andrzej Pająk, Sofia Malyutina, Růžena Kubínová, Abdonas Tamosiunas, Martin Bobak, Michail Katsoulis, Philippos Orfanos, Paolo Boffetta, Antonia Trichopoulou, Hermann Brenner, on behalf of the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES)

Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality. This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs. Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking. This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.