Vlaanderen, Jelle Portengen, Lutzen Schuz, Joachim Olsson, Ann Pesch, Beate Kendzia, Benjamin Stucker, Isabelle Guida, Florence Bruske, Irene Wichmann, Heinz-Erich Consonni, Dario Landi, Maria Teresa Caporaso, Neil Siemiatycki, Jack Merletti, Franco Mirabelli, Dario Richiardi, Lorenzo Gustavsson, Per Plato, Nils Jockel, Karl-Heinz Ahrens, Wolfgang Pohlabeln, Hermann Tardon, Adonina Zaridze, David Field, John K 't Mannetje, Andrea Pearce, Neil McLaughlin, John Demers, Paul Szeszenia-Dabrowska, Neonila Lissowska, Jolanta Rudnai, Peter Fabianova, Eleonora Stanescu Dumitru, Rodica Bencko, Vladimir Foretova, Lenka Janout, Vladimir Boffetta, Paolo Forastiere, Francesco Bueno-de-Mesquita, Bas Peters, Susan Bruning, Thomas Kromhout, Hans Straif, Kurt Vermeulen, Roel eng Canadian Institutes of Health Research/Canada Meta-Analysis Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't 2013/12/21 06:00 Am J Epidemiol. 2014 Feb 1;179(3):290-8. doi: 10.1093/aje/kwt273. Epub 2013 Dec 18. ; International audience ; The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.