title: 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.
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.
authors.forename: Jelle
authors.initials: J
authors.lastname: Vlaanderen
authors.forename: Lützen
authors.initials: L
authors.lastname: Portengen
authors.forename: Joachim
authors.initials: J
authors.lastname: Schüz
authors.forename: Ann
authors.initials: A
authors.lastname: Olsson
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kendzia
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stücker
authors.forename: Florence
authors.initials: F
authors.lastname: Guida
authors.forename: Irene
authors.initials: I
authors.lastname: Brüske
authors.forename: Heinz-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Dario
authors.initials: D
authors.lastname: Consonni
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.forename: Neil
authors.initials: N
authors.lastname: Caporaso
authors.forename: Jack
authors.initials: J
authors.lastname: Siemiatycki
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.forename: Dario
authors.initials: D
authors.lastname: Mirabelli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Richiardi
authors.forename: Per
authors.initials: P
authors.lastname: Gustavsson
authors.forename: Nils
authors.initials: N
authors.lastname: Plato
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ahrens
authors.forename: Hermann
authors.initials: H
authors.lastname: Pohlabeln
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: David
authors.initials: D
authors.lastname: Zaridze
authors.forename: John K
authors.initials: JK
authors.lastname: Field
authors.forename: Andrea
authors.initials: A
authors.lastname: 't Mannetje
authors.forename: Neil
authors.initials: N
authors.lastname: Pearce
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Paul
authors.initials: P
authors.lastname: Demers
authors.forename: Neonila
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fabianova
authors.forename: Rodica
authors.initials: R
authors.lastname: Stanescu Dumitru
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bencko
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Janout
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Francesco
authors.initials: F
authors.lastname: Forastiere
authors.forename: Bas
authors.initials: B
authors.lastname: Bueno-de-Mesquita
authors.forename: Susan
authors.initials: S
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Hans
authors.initials: H
authors.lastname: Kromhout
authors.forename: Kurt
authors.initials: K
authors.lastname: Straif
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
mesh_terms: D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D015987:Effect Modifier, Epidemiologic; D005060:Europe / Q000453:epidemiology; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D015233:Models, Statistical; D009520:New Zealand / Q000453:epidemiology; D016017:Odds Ratio; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D016540:Smoking Cessation / Q000706:statistics & numerical data; D013997:Time Factors
keywords: cigarette smoke; cumulative exposure; effect modification; lung cancer; pooled analysis