Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 179, Issue 3, Pages 290-298Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwt273
Keywords
cigarette smoke; cumulative exposure; effect modification; lung cancer; pooled analysis
Categories
Funding
- French Agency of Health Security
- Fondation de France
- French National Research Agency, the National Institute of Cancer
- Fondation for Medical Research
- The French Institute for Public Health Surveillance
- Health Ministry, the Organization for the Research on Cancer
- French Ministry of Work, Solidarity and Public Function
- Organization for the Research on Cancer
- Federal Ministry of Education, Science, Research, and Technology [01HK 173/0]
- Federal Ministry of Science [01 HK 546/8]
- Ministry of Labour and Social Affairs [IIIb7-27/13]
- The International Agency for Research on Cancer Multicenter Case-Control Study of Occupational, Environment and Lung Cancer in Central and Eastern Europe (INCO-COPERNICUS)
- European Commission's INCO-COPERNICUS program [IC15-CT96-0313]
- Polish State Committee for Scientific Research [SPUB-M-COPERNICUS/P-05/DZ-30/99/2000]
- Roy Castle Foundation
- Italian Association for Cancer Research, Region Piedmont
- Compagnia di San Paolo
- Fondo de Investigacion Sanitaria
- Ciber de Epidemiologia y Salud Publica, Spain
- Health Research Council of New Zealand
- New Zealand Department of Labour, Lottery Health Research
- Cancer Society of New Zealand
- International Agency for Research on Cancer
- European commission
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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 (19852009). 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 2030 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.
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