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American Journal of Epidemiology Advance Access first published online on June 4, 2007
This version published online on June 21, 2007

American Journal of Epidemiology, doi:10.1093/aje/kwm089
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American Journal of Epidemiology Published by the Johns Hopkins Bloomberg School of Public Health 2007.

Practice of Epidemiology

Cigarette Smoking and Cancer Risk: Modeling Total Exposure and Intensity

Jay H. Lubin1, Michael C. R. Alavanja2, Neil Caporaso3, Linda M. Brown1, Ross C. Brownson4, R. William Field5,6, Montserrat Garcia-Closas7, Patricia Hartge8, Michael Hauptmann1, Richard B. Hayes2, Ruth Kleinerman9, Manolis Kogevinas10,11, Daniel Krewski12, Bryan Langholz13, Ernest G. Létourneau14, Charles F. Lynch5, Núria Malats10, Dale P. Sandler15, Angelika Schaffrath-Rosario16, Janet B. Schoenberg17, Debra T. Silverman2, Zuoyuan Wang18, H.-Erich Wichmann19, Homer B. Wilcox17 and Jan M. Zielinski20,21

1 Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
2 Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
3 Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
4 Department of Community Health, School of Public Health, St. Louis University, St. Louis, MO
5 Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA
6 Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA
7 Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
8 Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
9 Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
10 Centre for Research in Environmental Epidemiology, Municipal Institute of Medical Research (IMIM), Barcelona, Spain
11 Department of Social Medicine, Medical School, University of Crete, Heraklion, Greece
12 McLaughlin Centre for Population Health Risk Assessment, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
13 Department of Preventive Medicine, School of Medicine, University of Southern California, Los Angeles, CA
14 Radiation Protection Bureau, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada
15 Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
16 Robert Koch-Institut, Abteilung Epidemiologie und Gesundheitsberichterstattung, Berlin, Germany
17 Cancer Epidemiology Services, New Jersey Department of Health and Senior Services, Trenton, NJ
18 Laboratory of Industrial Hygiene, Ministry of Health, Beijing, China
19 Institute of Epidemiology, National Research Center for Environment and Health (GSF), Neuherberg, Germany
20 Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada
21 Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

Correspondence to Dr. Jay H. Lubin, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rockville, MD 20852 (e-mail: lubinj{at}mail.nih.gov).

Received for publication August 11, 2006. Accepted for publication February 13, 2007.

A recent analysis showed that the excess odds ratio (EOR) for lung cancer due to smoking can be modeled by a function which is linear in total pack-years and exponential in the logarithm of smoking intensity and its square. Below 15–20 cigarettes per day, the EOR/pack-year increased with intensity (direct exposure rate or enhanced potency effect), suggesting greater risk for a total exposure delivered at higher intensity (for a shorter duration) than for an equivalent exposure delivered at lower intensity. Above 20 cigarettes per day, the EOR/pack-year decreased with increasing intensity (inverse exposure rate or reduced potency effect), suggesting greater risk for a total exposure delivered at lower intensity (for a longer duration) than for an equivalent exposure delivered at higher intensity. The authors applied this model to data from 10 case-control studies of cancer, including cancers of the lung, bladder, oral cavity, pancreas, and esophagus. At lower intensities, there was enhanced potency for several cancer sites, but narrow ranges for pack-years increased uncertainty, precluding definitive conclusions. At higher intensities, there was a consistent reduced potency effect across studies. The intensity effects were statistically homogeneous, indicating that after accounting for risk from total pack-years, intensity patterns were comparable across the diverse cancer sites.

case-control studies; epidemiologic methods; models, statistical; neoplasms; risk; smoking

Abbreviations: EOR, excess odds ratio; ESHS, European Smoking and Health Study; OR, odds ratio


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