Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: A flexible method applied to cigarette smoking and lung cancer in the SYNERGY study

Jelle Vlaanderen, Lützen Portengen, Joachim Schüz, Ann Olsson, Beate Pesch, Benjamin Kendzia, Isabelle Stücker, Florence Guida, Irene Brüske, Heinz Erich Wichmann, Dario Consonni, Maria Teresa Landi, Neil Caporaso, Jack Siemiatycki, Franco Merletti, Dario Mirabelli, Lorenzo Richiardi, Per Gustavsson, Nils Plato, Karl Heinz JöckelWolfgang Ahrens, Hermann Pohlabeln, Adonina Tardón, David Zaridze, John K. Field, Andrea 'T Mannetje, Neil Pearce, John McLaughlin, Paul Demers, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Rodica Stanescu Dumitru, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Paolo Boffetta, Francesco Forastiere, Bas Bueno-De-Mesquita, Susan Peters, Thomas Brüning, Hans Kromhout, Kurt Straif, Roel Vermeulen

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)290-298
Number of pages9
JournalAmerican Journal of Epidemiology
Volume179
Issue number3
DOIs
Publication statusPublished - Feb 2014

Keywords

  • cigarette smoke
  • cumulative exposure
  • effect modification
  • lung cancer
  • pooled analysis

ASJC Scopus subject areas

  • Epidemiology

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