ebooksclub.org How Tabacco Smoke Causes Diesease
How Tobacco Smoke Causes
Disease: The Biology and
Behavioral Basis for
Smoking-Attributable Disease
A Report of the Surgeon General
2010
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Office of the Surgeon General
Rockville, MD
National Library of Medicine Cataloging in Publication
How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable
disease : a report of the Surgeon General. – Rockville, MD : Dept. of Health and Human Services,
Public Health Service, Ofice of Surgeon General, 2010.
p. 704
Includes bibliographical references.
1.
Tobacco – adverse effects. 2. Smoking – adverse effects. 3. Disease – etiology. 4. Tobacco Use
Disorder – complications. 5. Tobacco Smoke Pollution – adverse effects. I. United States.
Public Health Service. Ofice of the Surgeon General. II. United States. Ofice on Smoking
and Health.
QV 137 H847 2010
U.S. Department of Health and Human Services
Centers for Disease Control and Prevention
National Center for Chronic Disease Prevention and Health Promotion
Ofice on Smoking and Health
This publication is available on the World Wide Web at
http://www.surgeongeneral.gov/library
Suggested Citation
U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology
and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta,
GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention,
National Center for Chronic Disease Prevention and Health Promotion, Ofice on Smoking and
Health, 2010.
For sale by the Superintendent of Documents, U.S. Government Printing Ofice, Washington, DC
20402. ISBN 978-0-16-084078-4
Use of trade names is for identiication only and does not constitute endorsement by the
U.S. Department of Health and Human Services. Any recommendations expressed by
nongovernmental individuals or organizations do not necessarily represent the views or opinions
of the U.S. Department of Health and Human Services.
Message from Kathleen Sebelius
Secretary of Health and Human Services
Tobacco use imposes enormous public health and inancial costs on this nation—costs that
are completely avoidable. Until we end tobacco use, more people will become addicted, more people will
become sick, more families will be devastated by the loss of loved ones, and the nation will continue
to incur damaging medical and lost productivity costs. Now is the time to fully implement proven and
effective interventions that reduce tobacco-caused death and disease and to help end this public health
epidemic once and for all.
Cigarettes are responsible for approximately 443,000 deaths—one in every ive deaths—each year
in the United States. The chronic diseases caused by tobacco use lead the causes of death and disability
in the United States and unnecessarily strain our health care system. The economic burden of cigarette
use includes more than $193 billion annually in health care costs and loss of productivity.
We can prevent the staggering toll that tobacco takes on individuals, families, and communities.
This new Surgeon General’s report focuses on cigarettes and cigarette smoke to provide further
evidence on how cigarettes cause addiction and premature death. It identiies better approaches to
helping people stop smoking and brings to light new ideas for how to lower the incidence of smokingcaused disease.
Twenty years of successful state efforts show that the more states invest in tobacco control
programs, the greater the reductions in smoking, and the longer states maintain such programs, the
greater and faster the impact. The largest impacts come when we increase tobacco prices, ban smoking
in public places, offer affordable and accessible cessation treatments and services, and combine media
campaigns with other initiatives. We have outlined a level of state investment in comprehensive
tobacco control and prevention efforts that, if implemented, would result in an estimated ive million
fewer smokers over the next ive years. Hundreds of thousands of premature deaths caused by tobacco
use could be prevented, and many fewer of the nations’ children would be deprived by premature
death of their aunts, uncles, parents, and grandparents. Importantly, in 2009 the U.S. Food and Drug
Administration received statutory authority to regulate tobacco products. This has the potential to lead
to even greater progress in reducing morbidity and mortality from tobacco use.
Tobacco prevention and control efforts need to be commensurate with the harm caused by tobacco
use. Otherwise, tobacco use will remain the largest cause of preventable illness and death in our nation
for decades to come. When we help Americans quit tobacco use and prevent our youth from ever
starting, we all beneit. Now is the time for comprehensive public health and regulatory approaches to
tobacco control. We have the knowledge and tools to largely eliminate tobacco caused disease. If we
seize this moment, we will make a difference in all of our communities and in the lives of generations
to come.
Foreword
In 1964, the irst Surgeon General’s report on the effects of smoking on health was released. In
the nearly 50 years since, extensive data from thousands of studies have consistently substantiated the
devastating effects of smoking on the lives of millions of Americans. Yet today in the United States,
tobacco use remains the single largest preventable cause of death and disease for both men and women.
Now, this 2010 report of the Surgeon General explains beyond a shadow of a doubt how tobacco smoke
causes disease, validates earlier indings, and expands and strengthens the science base. Armed with
this irrefutable data, the time has come to mount a full-scale assault on the tobacco epidemic.
More than 1,000 people are killed every day by cigarettes, and one-half of all long-term smokers
are killed by smoking-related diseases. A large proportion of these deaths are from early heart attacks,
chronic lung diseases, and cancers. For every person who dies from tobacco use, another 20 Americans
continue to suffer with at least one serious tobacco-related illness. But the harmful effects of smoking do not end with the smoker. Every year, thousands of nonsmokers die from heart disease and lung
cancer, and hundreds of thousands of children suffer from respiratory infections because of exposure
to secondhand smoke. There is no risk-free level of exposure to tobacco smoke, and there is no safe
tobacco product.
This new Surgeon General’s report describes in detail the ways tobacco smoke damages every
organ in the body and causes disease and death. We must build on our successes and more effectively
educate people about the health risks of tobacco use, prevent youth from ever using tobacco products,
expand access to proven cessation treatments and services, and reduce exposure to secondhand smoke.
Putting laws and other restrictions in place, including making tobacco products progressively less
affordable, will ultimately lead to our goal of a healthier America by reducing the devastating effects
of smoking.
The Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration
(FDA), and other federal agencies are diligently working toward this goal by implementing and supporting policies and regulations that strengthen our resolve to end the tobacco epidemic. CDC has
incorporated the World Health Organization’s MPOWER approach into its actions at the local, state,
and national levels. MPOWER consists of six key interventions proven to reduce tobacco use that can
prevent millions of deaths. CDC, along with federal, state, and local partners, is committed to monitoring the tobacco epidemic and prevention policies; protecting people from secondhand smoke where
they live, work, and play; offering quit assistance to current smokers; warning about the dangers of
tobacco; enforcing comprehensive restrictions on tobacco advertising, promotion, and sponsorship;
and raising taxes and prices on tobacco products.
In 2009, the Family Smoking Prevention and Tobacco Control Act was enacted, giving FDA
explicit regulatory authority over tobacco products to protect and promote the health of the American
public. Among other things, this historic legislation gave the agency the authority to require companies to reveal all of the ingredients in tobacco products—including the amount of nicotine—and to
prohibit the sale of tobacco products labeled as “light,” “mild,” or “low.” Further, with this new regulatory mandate, FDA will regulate tobacco advertising and require manufacturers to use more effective
warning labels, as well as restrict the access of young people to their products. FDA will also assess and
regulate modiied risk products, taking into account the impact their availability and marketing has on
initiation and cessation of tobacco use.
Reducing the tremendous toll of disease, disability, and death caused by tobacco use in the United
States is an urgent need and a shared responsibility. All public health agencies need to partner together
to develop common strategies to combat the dangers of smoking and tobacco use and defeat this
epidemic for good.
i
This 2010 Surgeon General’s report represents another important step in the developing recognition, both in this nation and around the world, that tobacco use is devastating to public health. Past
investments in research and in comprehensive tobacco control programs—combined with the indings
presented by this new report—provide the foundation, evidence, and impetus to increase the urgency
of our actions to end the epidemic of tobacco use.
Thomas R. Frieden, M.D., M.P.H.
Director
Centers for Disease Control and Prevention
and
Administrator
Agency for Toxic Substances and Disease Registry
ii
Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs
U.S. Food and Drug Administration
Preface
from the Surgeon General,
United States Public Health Service
In 1964, the Surgeon General released a landmark report on the dangers of smoking. During the
intervening 45 years, 29 Surgeon General’s reports have documented the overwhelming and conclusive
biologic, epidemiologic, behavioral, and pharmacologic evidence that tobacco use is deadly. Our newest
report, How Tobacco Smoke Causes Disease, is a comprehensive, scientiic discussion of how mainstream and secondhand smoke exposures damage the human body. Decades of research have enabled
scientists to identify the speciic mechanisms of smoking-related diseases and to characterize them in
great detail. Those biologic processes of cigarette smoke and disease are the focus of this report.
One-third of people who have ever tried smoking become daily smokers. This report investigates how and why smokers become addicted and documents how nicotine compares with heroin and
cocaine in its hold on users and its effects on the brain. The way tobacco is grown, mixed, and processed
today has made cigarettes more addictive than ever before. Because of this, the majority of smokers who
try to quit on their own typically require many attempts. It is imperative that we use this information to
prevent initiation, make tobacco products less addictive, and provide access to treatments and services
to help smokers quit successfully.
This new report also substantiates the evidence that there is no safe level of exposure to cigarette
smoke. When individuals inhale cigarette smoke, either directly or secondhand, they are inhaling more
than 7,000 chemicals: hundreds of these are hazardous, and at least 69 are known to cause cancer. The
chemicals are rapidly absorbed by cells in the body and produce disease-causing cellular changes. This
report explains those changes and identiies the mechanisms by which the major classes of the chemicals in cigarette smoke contribute to speciic disease processes. In addition, the report discusses how
chemicals in cigarette smoke impair the immune system and cause the kind of cellular damage that
leads to cancer and other diseases. Insight is provided as to why smokers are far more likely to suffer
from chronic disease than are nonsmokers.
By learning how tobacco smoke causes disease, we learn more about how chemicals harm cells,
how genes may make us susceptible, and how tobacco users become addicted to nicotine. The answers
to these questions will help us to more effectively prevent tobacco addiction and treat tobacco-caused
disease. Understanding the complexity of genetic, biochemical, and other inluences discussed in this
report offers the promise of reducing the disease burden from tobacco use through earlier detection
and better treatment; however, even with all of the science presented here, it currently remains true
that the only proven strategies to reduce the risks of tobacco-caused disease are preventing initiation,
facilitating cessation, and eliminating exposure to secondhand smoke.
My priority as Surgeon General is the health of the American people. Although we have made great
strides in tobacco control, more than 440,000 deaths each year are caused by smoking and exposure to
secondhand smoke. The cost to the nation is tremendous: a staggering amount is spent on medical care
and lost productivity. But most importantly there is immeasurable cost in human suffering and loss.
In 1964, Surgeon General Luther Terry called for “appropriate remedial actions” to address the
adverse effects of smoking. With this report, the devastating effects of smoking have been characterized in great detail and the need for appropriate remedial action is even more apparent. The harmful
effects of tobacco smoke do not end with the users of tobacco. There is no safe level of exposure to
tobacco smoke. Every inhalation of tobacco smoke exposes our children, our families, and our loved
ones to dangerous chemicals that can damage their bodies and result in life-threatening diseases such
as cancer and heart disease. And, although not a focus of this report, we know that smokeless tobacco
causes cancer and has other adverse health effects. The science is now clear that “appropriate remedial
actions” include protecting everyone in the country from having to breathe secondhand smoke; making all tobacco products progressively less affordable; expanding access to proven cessation treatments
iii
and services; taking actions at the federal, state, and local levels to counteract the inluence of tobacco
advertising, promotions, and sponsorship; and ensuring that all adults and children clearly understand
that the result of tobacco use is addiction, suffering, reduced quality of life, and all too often, early
death. Forty-ive years after Surgeon General Terry called on this nation to act, I say, if not now, when?
The health of our nation depends on it.
Regina Benjamin, M.D., M.B.A.
Surgeon General
iv
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Acknowledgments
This report was prepared by the U.S. Department of Health
and Human Services under the general direction of the
Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion,
Ofice on Smoking and Health.
Rear Admiral (Retired) David Rutstein, M.D., M.P.H., former Acting Deputy Surgeon General, U.S. Public Health
Service, Ofice of the Assistant Secretary for Health, Ofice
of the Surgeon General, Ofice of the Secretary, U.S.
Department of Health and Human Services, Washington,
D.C.
Vice Admiral Regina Benjamin, M.D., M.B.A., Surgeon
General, U.S. Public Health Service, Ofice of the Assistant
Secretary for Health, Ofice of the Surgeon General, Ofice
of the Secretary, U.S. Department of Health and Human
Services, Washington, D.C.
Rear Admiral (Retired) Robert C. Williams, P.E., D.E.E.,
former Acting Deputy Surgeon General, U.S. Public
Health Service, Ofice of the Surgeon General, Ofice of
the Assistant Secretary for Health, Ofice of the Secretary,
U.S. Department of Health and Human Services, Washington, D.C.
Rear Admiral Boris Lushniak, M.D., M.P.H., Deputy Surgeon General, U.S. Public Health Service, Ofice of the
Assistant Secretary for Health, Ofice of the Surgeon General, Ofice of the Secretary, U.S. Department of Health
and Human Services, Washington, D.C.
Thomas R. Frieden, M.D., M.P.H., Director, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Ursula Bauer, Ph.D., Director, National Center for Chronic
Disease Prevention and Health Promotion, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Rear Admiral Christopher Halliday, D.D.S., M.P.H., Chief
of Staff, U.S. Public Health Service, Ofice of the Assistant
Secretary for Health, Ofice of the Surgeon General, Ofice
of the Secretary, U.S. Department of Health and Human
Services, Washington, D.C.
Barbara Bowman, Ph.D., Associate Director for Science,
National Center for Chronic Disease Prevention and
Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Mary Beth Bigley, Dr.P.H., M.S.N., A.N.P., Acting Director of the Ofice of Science and Communication, Ofice of
the Surgeon General, Ofice of the Assistant Secretary for
Health, Ofice of the Secretary, U.S. Department of Health
and Human Services, Washington, D.C.
Samuel F. Posner, Ph.D., Associate Director for Science
(Acting), National Center for Chronic Disease Prevention
and Health Promotion, Centers for Disease Control and
Prevention, Atlanta, Georgia.
Rear Admiral (Retired) Steven K. Galson, M.D., M.P.H.,
former Acting Surgeon General, U.S. Public Health Service, Ofice of the Surgeon General, Ofice of the Assistant
Secretary for Health, Ofice of the Secretary, U.S. Department of Health and Human Services, Washington, D.C.
Tim A. McAfee, M.D., M.P.H., Director, Ofice on Smoking
and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Rear Admiral (Retired) Kenneth P. Moritsugu, M.D.,
M.P.H., former Acting Surgeon General, U.S. Public
Health Service, Ofice of the Surgeon General, Ofice of
Public Health and Science, Ofice of the Secretary, U.S.
Department of Health and Human Services, Washington,
D.C.
Terry F. Pechacek, Ph.D., Associate Director for Science, Ofice on Smoking and Health, National Center for
Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
The editors of the report were
Rear Admiral (Retired) Carol A. Romano, Ph.D., R.N.,
F.A.A.N., former Acting Deputy Surgeon General, U.S.
Public Health Service, Ofice of the Surgeon General,
Ofice of Public Health and Science, Ofice of the Secretary, U.S. Department of Health and Human Services,
Washington, D.C.
David Sidransky, M.D., Senior Scientiic Editor, Professor,
Otolaryngology-Head & Neck Surgery, Oncology, Pathology, Urology, Cellular and Molecular Medicine, and Director, Head and Neck Cancer Research, The Johns Hopkins
University School of Medicine, Johns Hopkins Medical
Institutions, Baltimore, Maryland.
v
Surgeon General’s Report
Leslie A. Norman, Managing Editor, Ofice on Smoking
and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Gayle C. Windham, Ph.D., M.S.P.H., Research Scientist
Supervisor, Chief, Environmental Surveillance Unit, Division of Environmental and Occupational Disease Control,
California Department of Public Health, Richmond, California.
Anne McCarthy, Technical Editor, Northrop Grumman
supporting National Center for Health Marketing, Division of Creative Services, Centers for Disease Control and
Prevention, Atlanta, Georgia.
Contributing authors were
David L. Ashley, Ph.D., Chief, Emergency Response and
Air Toxicants Branch, Division of Laboratory Sciences,
National Center for Environmental Health, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Peter L. Taylor, M.B.A., Technical Editor, Senior Editor,
Palladian Partners, Silver Spring, Maryland.
Timothy B. Baker, Ph.D., Professor of Medicine, University
of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Contributing editors were
David L. Ashley, Ph.D., Chief, Emergency Response and
Air Toxicants Branch, Division of Laboratory Sciences,
National Center for Environmental Health, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Steve A. Belinsky, Ph.D., Director, Lung Cancer Program,
Senior Scientist, Lovelace Respiratory Research Institute,
Albuquerque, New Mexico.
Neal L. Benowitz, M.D., Professor of Medicine and Biopharmaceutical Sciences and Chief, Division of Clinical
Pharmacology and Experimental Therapeutics, University
of California, San Francisco, California.
Neal L. Benowitz M.D., Professor of Medicine and Biopharmaceutical Sciences and Chief, Division of Clinical
Pharmacology and Experimental Therapeutics, University
of California, San Francisco, California.
Dorothy Hatsukami, Ph.D., Forster Family Professor in
Cancer Prevention, Professor of Psychiatry, University of
Minnesota Tobacco Use Research Center, University of
Minnesota, Minneapolis, Minnesota.
Tomoku Betsuyaku, M.D., Ph.D., Associate Professor, First
Department of Medicine, Hokkaido University School of
Medicine, Sapporo, Japan.
Stephen S. Hecht, Ph.D., Wallin Professor of Cancer Prevention, Masonic Cancer Center, University of Minnesota,
Minneapolis, Minnesota.
Ann M. Bode, Ph.D., Research Professor and Associate
Director, The Hormel Institute, University of Minnesota,
Austin, Minnesota.
Jack E. Henningield, Ph.D., Vice President Research and
Health Policy, Pinney Associates, Bethesda, Maryland; and
Professor, Adjunct, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of
Medicine, Baltimore, Maryland.
Anne Burke, M.D., Assistant Professor of Medicine, Gastroenterology Division, University of Pennsylvania School
of Medicine, Philadelphia, Pennsylvania.
David M. Burns, M.D., Professor Emeritus, Department of
Family and Preventive Medicine, School of Medicine, University of California, San Diego, California.
Patricia Richter, Ph.D., DABT, Toxicologist, Ofice on
Smoking and Health, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Rebecca Buus, Ph.D., Health Scientist, Maternal and Infant
Health Branch, Division of Reproductive Health, National
Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta,
Georgia.
Jonathan M. Samet, M.D., M.S., Professor and Chairman,
Department of Epidemiology, Bloomberg School of Public
Health, The Johns Hopkins University, Baltimore, Maryland (1994–2008); and Director, USC Institute for Global
Health, and Chairman, Department of Preventive Medicine, Keck School of Medicine, University of Southern
California, Los Angeles, California (2008–present).
Laurie Chassin, Ph.D., Regents Professor of Psychology,
Psychology Department, Arizona State University, Tempe,
Arizona.
vi
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
David Christiani, M.D., M.P.H., Professor, Departments of
Environmental Health and Epidemiology, Harvard School
of Public Health, Harvard University, Boston, Massachusetts.
Zigang Dong, M.D., M.S., Dr.P.H., Professor, The Hormel
Institute, University of Minnesota, Austin, Minnesota.
Björn Eliasson, M.D., Ph.D., Associate Professor, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Pamela I. Clark, M.S.P.H., Ph.D., Research Professor,
School of Public Health, University of Maryland, College
Park, Maryland.
Lucinda England, M.D., M.S.P.H., Medical Epidemiologist,
Maternal and Infant Health Branch, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
John P. Cooke, M.D., Ph.D., Professor of Medicine, Stanford University, Stanford, California.
Adolfo Correa, M.D., Ph.D., M.P.H., Medical Oficer, Division of Birth Defects and Developmental Disabilities,
National Center on Birth Defects and Developmental
Disabilities, Centers for Disease Control and Prevention,
Atlanta, Georgia.
Reginald Fant, Ph.D., Senior Scientist and Director, Pinney Associates, Bethesda, Maryland.
Garret A. FitzGerald, M.D., Chair, Department of Pharmacology, and Director, Institute for Translational Medicine
and Therapeutics, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania.
Johannes Czernin, M.D., Professor, Molecular and Medical
Pharmacology, and Chief, Ahmanson Biological Imaging
Division, David Geffen School of Medicine, University of
California, Los Angeles, California.
Mari S. Golub, Ph.D., Staff Toxicologist, Ofice of Environmental Health Hazard Assessment, California Environmental Protection Agency, Sacramento, California.
Gerald N. DeLorenze, Ph.D., Research Scientist, Division
of Research, Kaiser Permanente Northern California, Oakland, California.
Dorothy Hatsukami, Ph.D., Forster Family Professor in
Cancer Prevention, Professor of Psychiatry, University of
Minnesota Tobacco Use Research Center, University of
Minnesota, Minneapolis, Minnesota.
David M. DeMarini, Ph.D., Genetic Toxicologist, Integrated
Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
Stephen S. Hecht, Ph.D., Wallin Professor of Cancer Prevention, Masonic Cancer Center, University of Minnesota,
Minneapolis, Minnesota.
Delia Dempsey, M.D., M.S., Assistant Professor, Pediatrics,
Medicine and Clinical Pharmacology, Division of Clinical
Pharmacology, University of California, San Francisco,
San Francisco, California.
Phillip A. Dennis, M.D., Ph.D., Senior Investigator, Medical
Oncology Branch, Center for Cancer Research, National
Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
Marc K. Hellerstein, M.D., Ph.D., Professor (DH Calloway
Chair in Human Nutrition), Department of Nutritional
Sciences, University of California, Berkeley, California;
and Professor of Endocrinology, Metabolism and Nutrition, Department of Medicine, University of California,
San Francisco, California.
Yan Shirley Ding, Ph.D., Senior Service Fellow, Emergency Response and Air Toxicants Branch, Division of
Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention,
Atlanta, Georgia.
Jack E. Henningield, Ph.D., Vice President Research and
Health Policy, Pinney Associates, Bethesda, Maryland; and
Professor, Adjunct, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of
Medicine, Baltimore, Maryland.
Mirjana V. Djordjevic, Ph.D., Program Director, Tobacco
Control Research Branch, Behavioral Research Program,
Division of Cancer Control and Population Sciences,
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland.
Brian Hitsman, Ph.D., Assistant Professor, Department of
Preventive Medicine, Northwestern University, Chicago,
Illinois.
vii
Surgeon General’s Report
James C. Hogg, M.D., Ph.D., Emeritus Professor of
Pathology and Lab Medicine, iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia and St. Paul’s Hospital, Vancouver, British
Columbia, Canada.
Raymond Niaura, Ph.D., Professor, Department of Psychiatry and Human Behavior, The Warren Alpert
Medical School of Brown University; and Director, Transdisciplinary Research, Butler Hospital, Providence, Rhode
Island.
Anne M. Joseph, M.D., M.P.H., Wexler Professor of Medicine, and Director, Applied Clinical Research Program,
University of Minnesota Medical School, Minneapolis,
Minnesota.
James Pankow, Ph.D., Professor, Department of Chemistry, and Department of Civil and Environmental Engineering, Portland State University, Portland, Oregon.
Steve Pappas, Ph.D., Research Chemist, Emergency
Response and Air Toxicants Branch, Division of Laboratory
Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Caryn Lerman, Ph.D., Mary W. Calkins Professor, Department of Psychiatry and Annenberg Public Policy Center;
and Director, Tobacco Use Research Center, Scientiic
Director, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Terry F. Pechacek, Ph.D., Associate Director for Science,
Ofice on Smoking and Health, National Center for
Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
William MacNee, Professor, ELEGI Colt Research Labs,
MRC Centre for Inlammation Research, The Queen’s
Medical Research Institute, University of Edinburgh,
Edinburgh, Scotland, United Kingdom.
Kenneth A. Perkins, Ph.D., Professor of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Athina Markou, Ph.D., Professor, Department of Psychiatry, School of Medicine, University of California, San
Diego, La Jolla, California.
Lisa A. Peterson, Ph.D., Professor, Masonic Cancer Center
and the Division of Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota.
Robert Merritt, M.A., Branch Chief, Epidemiology and
Surveillance Branch, Division of Heart Disease and Stroke
Prevention, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Gerd P. Pfeifer, Ph.D., Professor and Chair, Division of Biology, Beckman Research Institute, City of Hope National
Medical Center, Duarte, California.
Dennis L. Molfese, Ph.D., Distinguished University Scholar
and Professor, Birth Defects Center, University of Louisville, Louisville, Kentucky.
Halit Pinar, M.D., Director, Division of Perinatal and Pediatric Pathology, Women and Infants Hospital of Rhode
Island; and Professor, Department of Pathology and Laboratory Medicine, Brown University Alpert School of Medicine, Providence, Rhode Island.
Masaaki Moriya, Ph.D., Research Professor, Laboratory of
Chemical Biology, Department of Pharmacological Sciences, University at Stony Brook, The State University of
New York, Stony Brook, New York.
Gregory Polzin, Ph.D., Research Chemist, Emergency
Response and Air Toxicants Branch, Division of Laboratory
Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Marcus Munafò, M.A., M.Sc., Ph.D., Reader in Biological
Psychology, Department of Experimental Psychology, University of Bristol, Bristol, United Kingdom.
Patricia Richter, Ph.D., DABT, Toxicologist, Ofice on
Smoking and Health, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Sharon E. Murphy, Ph.D., Professor, Biochemistry, Molecular Biology and BioPhysics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Nancy Rigotti, M.D., Professor of Medicine, Harvard Medical School; and Director, Tobacco Research and Treatment
Center, Massachusetts General Hospital, Boston, Massachusetts.
viii
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Wendie A. Robbins, Ph.D., Associate Professor, UCLA
Schools of Nursing and Public Health, University of California, Los Angeles, California.
Weija (William) Wu, Ph.D., Senior Service Fellow, Emergency Response and Air Toxicants Branch, Division of
Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention,
Atlanta, Georgia.
Andrew G. Salmon, M.A., D.Phil., Senior Toxicologist,
Ofice of Environmental Health Hazard Assessment, California Department of Health Services, Oakland, California.
Mitchell Zeller, J.D., Vice President for Policy and Strategic Communications, Pinney Associates, Bethesda, Maryland.
Jonathan M. Samet, M.D., M.S., Professor and Chairman,
Department of Epidemiology, Bloomberg School of Public
Health, The Johns Hopkins University, Baltimore, Maryland (1994–2008); and Director, USC Institute for Global
Health, and Chairman, Department of Preventive Medicine, Keck School of Medicine, University of Southern
California, Los Angeles, California (2008–present).
Reviewers were
Erik M. Augustson, Ph.D., M.P.H., Behavioral Scientist/
Psychologist, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and
Population Sciences, National Cancer Institute, National
Institutes of Health, Bethesda, Maryland.
Robert M. Senior, M.D., Professor of Pulmonary Medicine,
Cell Biology & Physiology, Division of Pulmonary and
Critical Care, Washington University School of Medicine,
St. Louis, Missouri.
Cathy L. Backinger, Ph.D., M.P.H., Chief, Tobacco Control
Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National
Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
Edwin K. Silverman, M.D., Ph.D., Associate Professor of
Medicine, Harvard Medical School, Harvard University;
and Associate Physician, Brigham and Women’s Hospital,
Boston, Massachusetts.
Neal L. Benowitz M.D., Professor of Medicine and Biopharmaceutical Sciences and Chief, Division of Clinical
Pharmacology and Experimental Therapeutics, University
of California, San Francisco, California.
Margaret R. Spitz, M.D., M.P.H., Professor and Chair,
Department of Epidemiology, The University of Texas,
M. D. Anderson Cancer Center, Houston, Texas.
Mary Beth Bigley, Dr.P.H., M.S.N., A.N.P., Acting Director of the Ofice of Science and Communication, Ofice
of the Surgeon General, Ofice of Public Health and Science, Ofice of the Secretary, U.S. Department of Health
and Human Services, Washington, D.C.
Stephen B. Stanill, M.S., Chemist, Emergency Response
and Air Toxicants Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Prudence Talbot, Ph.D., Professor of Cell Biology, Department of Cell Biology and Neuroscience, University of California, Riverside, California.
Michele Bloch, M.D., Ph.D., Medical Oficer, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National
Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
Anne Thorndike, M.D., M.P.H., Instructor in Medicine,
General Medicine Unit, Massachusetts General Hospital,
Boston, Massachusetts.
Naomi Breslau, Ph.D., Professor, Department of Epidemiology, Michigan State University, East Lansing, Michigan.
Clifford H. Watson, Ph.D., Lead Research Chemist, Emergency Response and Air Toxicants Branch, National Center for Environmental Health, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Klaus D. Brunnemann, M.S., Research Associate, New
York Medical College, Valhalla, New York.
David M. Burns, M.D., Professor Emeritus, Department of
Family and Preventive Medicine, School of Medicine, University of California, San Diego, California.
Gayle C. Windham, Ph.D., M.S.P.H., Research Scientist
Supervisor, Chief, Environmental Surveillance Unit, Division of Environmental and Occupational Disease Control,
California Department of Public Health, Richmond, California.
ix
Surgeon General’s Report
Pamela I. Clark, M.S.P.H., Ph.D., Research Professor,
School of Public Health, University of Maryland, College
Park, Maryland.
Stanton Glantz, Ph.D., Professor of Medicine, Division of
Cardiology, University of California, San Francisco, California.
Gregory N. Connolly, D.M.D., M.P.H., Professor, Department of Society, Human Development, and Health, Harvard School of Public Health, Harvard University, Boston,
Massachusetts.
Michael R. Guerin, Ph.D., Associate Division Director
(retired), Oak Ridge National Laboratory, Knoxville, Tennessee.
Dorothy Hatsukami, Ph.D., Forster Family Professor in
Cancer Prevention, Professor of Psychiatry, University of
Minnesota Tobacco Use Research Center, University of
Minnesota, Minneapolis, Minnesota.
William A. Corrigall, Ph.D., Professor of Psychiatry, University of Minnesota; and Senior Scientist, Minneapolis
Medical Research Foundation, Minneapolis, Minnesota.
James D. Crapo, M.D., Professor of Medicine, National
Jewish Health, Denver, Colorado.
Jack E. Henningield, Ph.D., Vice President Research and
Health Policy, Pinney Associates, Bethesda, Maryland; and
Professor, Adjunct, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of
Medicine, Baltimore, Maryland.
Michael Criqui, M.D., M.P.H., Professor and Chief, Division of Preventive Medicine, Department of Family and
Preventive Medicine; and Professor, Department of Medicine, School of Medicine, University of California, San
Diego, La Jolla, California.
Allison Chausmer Hoffman, Ph.D., Program Director,
National Institute on Drug Abuse, National Institutes of
Health, Bethesda, Maryland.
K. Michael Cummings, Ph.D., M.P.H., Senior Research
Scientist, Chair, Department of Health Behavior, Division
of Cancer Prevention and Population Sciences, Roswell
Park Cancer Institute, Buffalo, New York.
John R. Hoidal, M.D., Professor and Chairman of Medicine, School of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah.
Mirjana V. Djordjevic, Ph.D., Program Director, Tobacco
Control Research Branch, Behavioral Research Program,
Division of Cancer Control and Population Sciences,
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland.
John E. Hokanson, Ph.D., Associate Professor and Chair,
Department of Epidemiology, Colorado School of Public
Health, University of Colorado, Denver, Aurora, Colorado.
John Hughes, M.D., Professor, Department of Psychiatry,
University of Vermont, Burlington, Vermont.
Erik Dybing, M.D., Ph.D., Division Director and Professor
(retired), Division of Environmental Health, Norwegian
Institute of Public Health, Oslo, Norway.
Richard D. Hurt, M.D., Professor of Medicine, Mayo Clinic
College of Medicine, Rochester, Minnesota.
Michael Eriksen, Sc.D., Professor, and Director, Institute
of Public Health, Georgia State University, Atlanta, Georgia.
Jared B. Jobe, Ph.D., FABMR, Program Director, Clinical
Applications and Prevention Branch, Division of Prevention and Population Sciences, National Heart, Lung, and
Blood Institute, National Institutes of Health, Bethesda,
Maryland.
Jefferson Fowles, Ph.D., Toxicologist, LyondellBasell
Industries, Rotterdam, The Netherlands.
Rachel Kaufmann, Ph.D., M.P.H., Deputy Associate Director for Science, Ofice on Smoking and Health, National
Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta,
Georgia.
Adi F. Gazdar, M.D., Professor, Department of Pathology,
University of Texas Southwestern Medical Center, Dallas,
Texas.
Gary A. Giovino, Ph.D., M.S., Professor and Chair, Department of Health Behavior, School of Public Health and
Health Professions, University at Buffalo, The State University of New York, Buffalo, New York.
Karl T. Kelsey, M.D., M.O.H., Professor, Community
Health and Pathology and Laboratory Medicine, Director,
Center for Environmental Health and Technology, Brown
University, Providence, Rhode Island.
x
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Juliette Kendrick, M.D., Medical Officer, Division of
Reproductive Health, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Wallace Pickworth, Ph.D., Health Research Leader, Battelle Centers for Public Health Research and Evaluation,
Baltimore, Maryland.
John M. Pinney, President, Pinney Associates, Bethesda,
Maryland.
Martin Kharrazi, Ph.D., Chief, Program Research and
Demonstration Section, Genetic Disease Screening Program, California Department of Public Health, Richmond,
California.
Britt C. Reid, D.D.S., Ph.D., Chief, Modiiable Risk Factors
Branch, Epidemiology and Genetics Research Program,
Division of Cancer Control and Population Sciences,
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland.
Taline V. Khroyan, Ph.D., Behavioral Pharmacologist, SRI
International, Center for Health Sciences, Menlo Park,
California.
John E. Repine, M.D., Director, Webb-Waring Center, Waring Professor of Medicine and Pediatrics, School of Medicine, University of Colorado, Denver, Colorado.
Walther N.M. Klerx, Food and Consumer Product Safety
Authority, Eindhoven, The Netherlands.
Philip Lazarus, Ph.D., Professor of Pharmacology, College
of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, Pennsylvania.
William Rickert, Ph.D., Chief Executive Oficer, Labstat
International ULC, Kitchener, Ontario, Canada.
David J. Riley, M.D., Professor, Department of Medicine,
University of Medicine and Dentistry of New Jersey, Robert
Wood Johnson Medical School, Piscataway, New Jersey.
Scott Leischow, Ph.D., Associate Director for Behavioral
and Social Sciences Research, Arizona Cancer Center, The
University of Arizona, Tucson, Arizona.
Scott Rogers, M.P.H., Public Health Advisor, Epidemiology
and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland.
Christina N. Lessov-Schlaggar, Ph.D., Research Assistant
Professor, Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
Catherine Lorraine, Director, Policy Development and
Coordination Staff, Food and Drug Administration, Silver
Spring, Maryland.
Dale P. Sandler, Ph.D., Chief, Epidemiology Branch,
National Institute of Environmental Health Sciences,
National Institutes of Health, Research Triangle Park,
North Carolina.
Cathy Melvin, Ph.D., M.P.H., Director, Child Health Services Program, Cecil G. Sheps Center for Health Services
Research, University of North Carolina, Chapel Hill, North
Carolina.
David A. Scott, Ph.D., Associate Professor, Oral Health and
Systemic Disease Research Group, University of Louisville, Louisville, Kentucky.
John D. Minna, M.D., Director, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.
Harold E. Seifried, Ph.D., DABT, Chemist, Toxicologist,
Industrial Hygienist (retired), Program Director, Nutritional Sciences Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland.
Joshua E. Muscat, Ph.D., Professor, Department of Public
Health Sciences, College of Medicine, Pennsylvania State
University, Milton S. Hershey Medical Center, Hershey,
Pennsylvania.
Peter G. Shields, M.D., Professor of Medicine and Oncology, Deputy Director, Lombardi Comprehensive Cancer
Center, Georgetown University Medical Center, Washington, D.C.
Mark Parascandola, Ph.D., M.P.H., Epidemiologist,
Tobacco Control Research Branch, Behavioral Research
Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland.
Saul Shiffman, Ph.D., Research Professor, Psychology and
Psychiatry, University of Pittsburgh; and Senior Scientiic
Advisor, Pinney Associates, Pittsburgh, Pennsylvania.
xi
Surgeon General’s Report
Donald R. Shopland, Sr., U.S. Public Health Service
(retired), Ringgold, Georgia.
Other contributors were
Charlotte Gerczak, M.L.A., Communications Associate,
Department of Epidemiology, Bloomberg School of Public
Health, The Johns Hopkins University, Baltimore, Maryland.
Stephen Sidney, M.D., M.P.H., Associate Director for Clinical Research, Division of Research, Kaiser Permanente,
Oakland, California.
Roberta B. Gray, Administrative Supervisor to Dr. Jonathan M. Samet, Department of Epidemiology, Bloomberg
School of Public Health, The Johns Hopkins University,
Baltimore, Maryland.
Gary D. Stoner, Ph.D., Professor Emeritus, Department of
Internal Medicine, The Ohio State University, Columbus,
Ohio.
Gary E. Swan, Ph.D., Director, Center for Health Sciences,
SRI International Fellow, SRI International, Center for
Health Sciences, Menlo Park, California.
Marta Gwinn, M.D., M.P.H., Medical Oficer, Ofice of Public Health Genomics, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Michael J. Thun, M.D., M.S., Vice President Emeritus, Epidemiology and Surveillance Research, American Cancer
Society, Atlanta, Georgia.
Nancy Leonard, Administrative Coordinator to Dr. Jonathan M. Samet, Department of Epidemiology, Bloomberg
School of Public Health, The Johns Hopkins University,
Baltimore, Maryland.
Robert B. Wallace, M.D., M.Sc., Irene Ensminger Stecher
Professor of Epidemiology and Internal Medicine, Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa.
Deborah Williams, Desktop Publishing Specialist to Dr.
Jonathan M. Samet, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Deborah M. Winn, Ph.D., Deputy Director, Epidemiology
and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland.
xii
How Tobacco Smoke Causes Disease: The Biology and
Behavioral Basis for Smoking-Attributable Disease
Chapter 1.
Introduction, Evaluation of Evidence on Mechanisms of Disease Production, and Summary 1
Introduction 3
Evaluation of Evidence on Mechanisms of Disease Production 5
Mechanisms of Action: Necessary, Suficient, or Neither 7
Description of Evidence on Mechanisms of Disease Production 8
Scientiic Basis of the Report 8
Development of the Report 8
Major Conclusions 9
Chapter Conclusions 9
References 12
Chapter 2.
The Changing Cigarette 13
Introduction 15
Cigarette Design Changes over the Years 15
New Cigarette Products 17
Low-Nicotine Cigarettes 18
Cigarette-Like Products 18
Evaluation of New Cigarette Products 19
New Oversight of Tobacco Products 20
Summary 20
Conclusions 21
References 22
Chapter 3.
Chemistry and Toxicology of Cigarette Smoke and Biomarkers of Exposure and Harm 27
Introduction 29
Chemistry 30
Biomarkers 51
Summary 77
Conclusions 79
References 80
Chapter 4.
Nicotine Addiction: Past and Present 103
Introduction 105
Deinition of Nicotine Addiction 105
Tobacco Constituents and Pharmacokinetics 111
Components of Nicotine Addiction 116
Pathophysiology of Nicotine Addiction 124
Genetics 137
Prevalence and Trajectory Toward Nicotine Dependence 156
Epidemiology of Tobacco Use and Nicotine Dependence in Adults 162
Trajectory of Recovery or Relapse 170
xiii
Evidence Summary 180
Conclusions 183
References 184
Chapter 5.
Cancer 221
Introduction 225
Carcinogen Exposure, Metabolism, and DNA Adducts 227
DNA Repair and Conversion of Adducts to Mutations 252
Gene Mutations in Tobacco-Induced Cancer 274
Loss of Mechanisms for Growth Control 284
Other Aspects 296
Evidence Summary 302
Conclusions 304
References 305
Chapter 6.
Cardiovascular Diseases 351
Introduction 355
Tobacco Use and Cardiovascular Disease 355
Secondhand Tobacco Smoke and Cardiovascular Disease 363
Pathophysiology 363
Hemodynamic Effects 368
Smoking and the Endothelium 370
Thrombogenic Effects 374
Inlammation 382
Smoking and Diabetes 383
Lipid Abnormalities 387
Cardiovascular Biomarkers 391
Smoking Cessation and Cardiovascular Disease 394
Methods to Reduce Exposure 402
Evidence Summary 407
Conclusions 408
References 409
Chapter 7.
Pulmonary Diseases 435
Introduction 437
Smoking and Respiratory Defense Mechanisms 450
Oxidative Stress 457
Oxidative Stress in Chronic Obstructive Pulmonary Disease 471
Genetics of Pulmonary Disease and Susceptibility to Tobacco Smoke 475
Pathogenesis of Emphysema 487
Summary 494
Evidence Summary 494
Conclusions 496
Implications 496
References 497
Chapter 8.
Reproductive and Developmental Effects 521
Introduction 523
xiv
Review of Epidemiologic Literature on Smoking 524
Pathophysiological and Cellular and Molecular Mechanisms of Smoking 555
Implications 606
Evidence Summary 608
Conclusions 612
References 613
Chapter 9.
A Vision for the Future 645
The Global Tobacco Epidemic 647
Reducing the Risks from Smoking 651
Ending the Tobacco Epidemic 652
Concluding Remarks 654
Appendix 9.1: Recommendations for Future Research 655
Appendix 9.2: Ending the Tobacco Problem: A Blueprint for the Nation 660
Appendix 9.3: Promoting Healthy Lifestyles: Policy, Program, and Personal Recommendations for
Reducing Cancer Risk 664
References 667
List of Abbreviations
671
List of Tables and Figures
675
Deinitions and Alternative Nomenclature of Genetic Symbols Used in This Report 679
Index
689
xv
Chapter 1
Introduction, Evaluation of Evidence on
Mechanisms of Disease Production, and Summary
Introduction 3
Evaluation of Evidence on Mechanisms of Disease Production 5
Mechanisms of Action: Necessary, Suficient, or Neither 7
Description of Evidence on Mechanisms of Disease Production 8
Scientiic Basis of the Report 8
Development of the Report 8
Major Conclusions
9
Chapter Conclusions 9
Chapter 2. The Changing Cigarette 9
Chapter 3. Chemistry and Toxicology of Cigarette Smoke and Biomarkers of Exposure and Harm 9
Chapter 4. Nicotine Addiction: Past and Present 10
Chapter 5. Cancer 10
Chapter 6. Cardiovascular Diseases 10
Chapter 7. Pulmonary Diseases 11
Chapter 8. Reproductive and Developmental Effects 11
References
12
1
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Introduction
Since the irst of the series in 19
Disease: The Biology and
Behavioral Basis for
Smoking-Attributable Disease
A Report of the Surgeon General
2010
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Office of the Surgeon General
Rockville, MD
National Library of Medicine Cataloging in Publication
How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable
disease : a report of the Surgeon General. – Rockville, MD : Dept. of Health and Human Services,
Public Health Service, Ofice of Surgeon General, 2010.
p. 704
Includes bibliographical references.
1.
Tobacco – adverse effects. 2. Smoking – adverse effects. 3. Disease – etiology. 4. Tobacco Use
Disorder – complications. 5. Tobacco Smoke Pollution – adverse effects. I. United States.
Public Health Service. Ofice of the Surgeon General. II. United States. Ofice on Smoking
and Health.
QV 137 H847 2010
U.S. Department of Health and Human Services
Centers for Disease Control and Prevention
National Center for Chronic Disease Prevention and Health Promotion
Ofice on Smoking and Health
This publication is available on the World Wide Web at
http://www.surgeongeneral.gov/library
Suggested Citation
U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology
and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta,
GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention,
National Center for Chronic Disease Prevention and Health Promotion, Ofice on Smoking and
Health, 2010.
For sale by the Superintendent of Documents, U.S. Government Printing Ofice, Washington, DC
20402. ISBN 978-0-16-084078-4
Use of trade names is for identiication only and does not constitute endorsement by the
U.S. Department of Health and Human Services. Any recommendations expressed by
nongovernmental individuals or organizations do not necessarily represent the views or opinions
of the U.S. Department of Health and Human Services.
Message from Kathleen Sebelius
Secretary of Health and Human Services
Tobacco use imposes enormous public health and inancial costs on this nation—costs that
are completely avoidable. Until we end tobacco use, more people will become addicted, more people will
become sick, more families will be devastated by the loss of loved ones, and the nation will continue
to incur damaging medical and lost productivity costs. Now is the time to fully implement proven and
effective interventions that reduce tobacco-caused death and disease and to help end this public health
epidemic once and for all.
Cigarettes are responsible for approximately 443,000 deaths—one in every ive deaths—each year
in the United States. The chronic diseases caused by tobacco use lead the causes of death and disability
in the United States and unnecessarily strain our health care system. The economic burden of cigarette
use includes more than $193 billion annually in health care costs and loss of productivity.
We can prevent the staggering toll that tobacco takes on individuals, families, and communities.
This new Surgeon General’s report focuses on cigarettes and cigarette smoke to provide further
evidence on how cigarettes cause addiction and premature death. It identiies better approaches to
helping people stop smoking and brings to light new ideas for how to lower the incidence of smokingcaused disease.
Twenty years of successful state efforts show that the more states invest in tobacco control
programs, the greater the reductions in smoking, and the longer states maintain such programs, the
greater and faster the impact. The largest impacts come when we increase tobacco prices, ban smoking
in public places, offer affordable and accessible cessation treatments and services, and combine media
campaigns with other initiatives. We have outlined a level of state investment in comprehensive
tobacco control and prevention efforts that, if implemented, would result in an estimated ive million
fewer smokers over the next ive years. Hundreds of thousands of premature deaths caused by tobacco
use could be prevented, and many fewer of the nations’ children would be deprived by premature
death of their aunts, uncles, parents, and grandparents. Importantly, in 2009 the U.S. Food and Drug
Administration received statutory authority to regulate tobacco products. This has the potential to lead
to even greater progress in reducing morbidity and mortality from tobacco use.
Tobacco prevention and control efforts need to be commensurate with the harm caused by tobacco
use. Otherwise, tobacco use will remain the largest cause of preventable illness and death in our nation
for decades to come. When we help Americans quit tobacco use and prevent our youth from ever
starting, we all beneit. Now is the time for comprehensive public health and regulatory approaches to
tobacco control. We have the knowledge and tools to largely eliminate tobacco caused disease. If we
seize this moment, we will make a difference in all of our communities and in the lives of generations
to come.
Foreword
In 1964, the irst Surgeon General’s report on the effects of smoking on health was released. In
the nearly 50 years since, extensive data from thousands of studies have consistently substantiated the
devastating effects of smoking on the lives of millions of Americans. Yet today in the United States,
tobacco use remains the single largest preventable cause of death and disease for both men and women.
Now, this 2010 report of the Surgeon General explains beyond a shadow of a doubt how tobacco smoke
causes disease, validates earlier indings, and expands and strengthens the science base. Armed with
this irrefutable data, the time has come to mount a full-scale assault on the tobacco epidemic.
More than 1,000 people are killed every day by cigarettes, and one-half of all long-term smokers
are killed by smoking-related diseases. A large proportion of these deaths are from early heart attacks,
chronic lung diseases, and cancers. For every person who dies from tobacco use, another 20 Americans
continue to suffer with at least one serious tobacco-related illness. But the harmful effects of smoking do not end with the smoker. Every year, thousands of nonsmokers die from heart disease and lung
cancer, and hundreds of thousands of children suffer from respiratory infections because of exposure
to secondhand smoke. There is no risk-free level of exposure to tobacco smoke, and there is no safe
tobacco product.
This new Surgeon General’s report describes in detail the ways tobacco smoke damages every
organ in the body and causes disease and death. We must build on our successes and more effectively
educate people about the health risks of tobacco use, prevent youth from ever using tobacco products,
expand access to proven cessation treatments and services, and reduce exposure to secondhand smoke.
Putting laws and other restrictions in place, including making tobacco products progressively less
affordable, will ultimately lead to our goal of a healthier America by reducing the devastating effects
of smoking.
The Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration
(FDA), and other federal agencies are diligently working toward this goal by implementing and supporting policies and regulations that strengthen our resolve to end the tobacco epidemic. CDC has
incorporated the World Health Organization’s MPOWER approach into its actions at the local, state,
and national levels. MPOWER consists of six key interventions proven to reduce tobacco use that can
prevent millions of deaths. CDC, along with federal, state, and local partners, is committed to monitoring the tobacco epidemic and prevention policies; protecting people from secondhand smoke where
they live, work, and play; offering quit assistance to current smokers; warning about the dangers of
tobacco; enforcing comprehensive restrictions on tobacco advertising, promotion, and sponsorship;
and raising taxes and prices on tobacco products.
In 2009, the Family Smoking Prevention and Tobacco Control Act was enacted, giving FDA
explicit regulatory authority over tobacco products to protect and promote the health of the American
public. Among other things, this historic legislation gave the agency the authority to require companies to reveal all of the ingredients in tobacco products—including the amount of nicotine—and to
prohibit the sale of tobacco products labeled as “light,” “mild,” or “low.” Further, with this new regulatory mandate, FDA will regulate tobacco advertising and require manufacturers to use more effective
warning labels, as well as restrict the access of young people to their products. FDA will also assess and
regulate modiied risk products, taking into account the impact their availability and marketing has on
initiation and cessation of tobacco use.
Reducing the tremendous toll of disease, disability, and death caused by tobacco use in the United
States is an urgent need and a shared responsibility. All public health agencies need to partner together
to develop common strategies to combat the dangers of smoking and tobacco use and defeat this
epidemic for good.
i
This 2010 Surgeon General’s report represents another important step in the developing recognition, both in this nation and around the world, that tobacco use is devastating to public health. Past
investments in research and in comprehensive tobacco control programs—combined with the indings
presented by this new report—provide the foundation, evidence, and impetus to increase the urgency
of our actions to end the epidemic of tobacco use.
Thomas R. Frieden, M.D., M.P.H.
Director
Centers for Disease Control and Prevention
and
Administrator
Agency for Toxic Substances and Disease Registry
ii
Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs
U.S. Food and Drug Administration
Preface
from the Surgeon General,
United States Public Health Service
In 1964, the Surgeon General released a landmark report on the dangers of smoking. During the
intervening 45 years, 29 Surgeon General’s reports have documented the overwhelming and conclusive
biologic, epidemiologic, behavioral, and pharmacologic evidence that tobacco use is deadly. Our newest
report, How Tobacco Smoke Causes Disease, is a comprehensive, scientiic discussion of how mainstream and secondhand smoke exposures damage the human body. Decades of research have enabled
scientists to identify the speciic mechanisms of smoking-related diseases and to characterize them in
great detail. Those biologic processes of cigarette smoke and disease are the focus of this report.
One-third of people who have ever tried smoking become daily smokers. This report investigates how and why smokers become addicted and documents how nicotine compares with heroin and
cocaine in its hold on users and its effects on the brain. The way tobacco is grown, mixed, and processed
today has made cigarettes more addictive than ever before. Because of this, the majority of smokers who
try to quit on their own typically require many attempts. It is imperative that we use this information to
prevent initiation, make tobacco products less addictive, and provide access to treatments and services
to help smokers quit successfully.
This new report also substantiates the evidence that there is no safe level of exposure to cigarette
smoke. When individuals inhale cigarette smoke, either directly or secondhand, they are inhaling more
than 7,000 chemicals: hundreds of these are hazardous, and at least 69 are known to cause cancer. The
chemicals are rapidly absorbed by cells in the body and produce disease-causing cellular changes. This
report explains those changes and identiies the mechanisms by which the major classes of the chemicals in cigarette smoke contribute to speciic disease processes. In addition, the report discusses how
chemicals in cigarette smoke impair the immune system and cause the kind of cellular damage that
leads to cancer and other diseases. Insight is provided as to why smokers are far more likely to suffer
from chronic disease than are nonsmokers.
By learning how tobacco smoke causes disease, we learn more about how chemicals harm cells,
how genes may make us susceptible, and how tobacco users become addicted to nicotine. The answers
to these questions will help us to more effectively prevent tobacco addiction and treat tobacco-caused
disease. Understanding the complexity of genetic, biochemical, and other inluences discussed in this
report offers the promise of reducing the disease burden from tobacco use through earlier detection
and better treatment; however, even with all of the science presented here, it currently remains true
that the only proven strategies to reduce the risks of tobacco-caused disease are preventing initiation,
facilitating cessation, and eliminating exposure to secondhand smoke.
My priority as Surgeon General is the health of the American people. Although we have made great
strides in tobacco control, more than 440,000 deaths each year are caused by smoking and exposure to
secondhand smoke. The cost to the nation is tremendous: a staggering amount is spent on medical care
and lost productivity. But most importantly there is immeasurable cost in human suffering and loss.
In 1964, Surgeon General Luther Terry called for “appropriate remedial actions” to address the
adverse effects of smoking. With this report, the devastating effects of smoking have been characterized in great detail and the need for appropriate remedial action is even more apparent. The harmful
effects of tobacco smoke do not end with the users of tobacco. There is no safe level of exposure to
tobacco smoke. Every inhalation of tobacco smoke exposes our children, our families, and our loved
ones to dangerous chemicals that can damage their bodies and result in life-threatening diseases such
as cancer and heart disease. And, although not a focus of this report, we know that smokeless tobacco
causes cancer and has other adverse health effects. The science is now clear that “appropriate remedial
actions” include protecting everyone in the country from having to breathe secondhand smoke; making all tobacco products progressively less affordable; expanding access to proven cessation treatments
iii
and services; taking actions at the federal, state, and local levels to counteract the inluence of tobacco
advertising, promotions, and sponsorship; and ensuring that all adults and children clearly understand
that the result of tobacco use is addiction, suffering, reduced quality of life, and all too often, early
death. Forty-ive years after Surgeon General Terry called on this nation to act, I say, if not now, when?
The health of our nation depends on it.
Regina Benjamin, M.D., M.B.A.
Surgeon General
iv
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Acknowledgments
This report was prepared by the U.S. Department of Health
and Human Services under the general direction of the
Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion,
Ofice on Smoking and Health.
Rear Admiral (Retired) David Rutstein, M.D., M.P.H., former Acting Deputy Surgeon General, U.S. Public Health
Service, Ofice of the Assistant Secretary for Health, Ofice
of the Surgeon General, Ofice of the Secretary, U.S.
Department of Health and Human Services, Washington,
D.C.
Vice Admiral Regina Benjamin, M.D., M.B.A., Surgeon
General, U.S. Public Health Service, Ofice of the Assistant
Secretary for Health, Ofice of the Surgeon General, Ofice
of the Secretary, U.S. Department of Health and Human
Services, Washington, D.C.
Rear Admiral (Retired) Robert C. Williams, P.E., D.E.E.,
former Acting Deputy Surgeon General, U.S. Public
Health Service, Ofice of the Surgeon General, Ofice of
the Assistant Secretary for Health, Ofice of the Secretary,
U.S. Department of Health and Human Services, Washington, D.C.
Rear Admiral Boris Lushniak, M.D., M.P.H., Deputy Surgeon General, U.S. Public Health Service, Ofice of the
Assistant Secretary for Health, Ofice of the Surgeon General, Ofice of the Secretary, U.S. Department of Health
and Human Services, Washington, D.C.
Thomas R. Frieden, M.D., M.P.H., Director, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Ursula Bauer, Ph.D., Director, National Center for Chronic
Disease Prevention and Health Promotion, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Rear Admiral Christopher Halliday, D.D.S., M.P.H., Chief
of Staff, U.S. Public Health Service, Ofice of the Assistant
Secretary for Health, Ofice of the Surgeon General, Ofice
of the Secretary, U.S. Department of Health and Human
Services, Washington, D.C.
Barbara Bowman, Ph.D., Associate Director for Science,
National Center for Chronic Disease Prevention and
Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
Mary Beth Bigley, Dr.P.H., M.S.N., A.N.P., Acting Director of the Ofice of Science and Communication, Ofice of
the Surgeon General, Ofice of the Assistant Secretary for
Health, Ofice of the Secretary, U.S. Department of Health
and Human Services, Washington, D.C.
Samuel F. Posner, Ph.D., Associate Director for Science
(Acting), National Center for Chronic Disease Prevention
and Health Promotion, Centers for Disease Control and
Prevention, Atlanta, Georgia.
Rear Admiral (Retired) Steven K. Galson, M.D., M.P.H.,
former Acting Surgeon General, U.S. Public Health Service, Ofice of the Surgeon General, Ofice of the Assistant
Secretary for Health, Ofice of the Secretary, U.S. Department of Health and Human Services, Washington, D.C.
Tim A. McAfee, M.D., M.P.H., Director, Ofice on Smoking
and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Rear Admiral (Retired) Kenneth P. Moritsugu, M.D.,
M.P.H., former Acting Surgeon General, U.S. Public
Health Service, Ofice of the Surgeon General, Ofice of
Public Health and Science, Ofice of the Secretary, U.S.
Department of Health and Human Services, Washington,
D.C.
Terry F. Pechacek, Ph.D., Associate Director for Science, Ofice on Smoking and Health, National Center for
Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
The editors of the report were
Rear Admiral (Retired) Carol A. Romano, Ph.D., R.N.,
F.A.A.N., former Acting Deputy Surgeon General, U.S.
Public Health Service, Ofice of the Surgeon General,
Ofice of Public Health and Science, Ofice of the Secretary, U.S. Department of Health and Human Services,
Washington, D.C.
David Sidransky, M.D., Senior Scientiic Editor, Professor,
Otolaryngology-Head & Neck Surgery, Oncology, Pathology, Urology, Cellular and Molecular Medicine, and Director, Head and Neck Cancer Research, The Johns Hopkins
University School of Medicine, Johns Hopkins Medical
Institutions, Baltimore, Maryland.
v
Surgeon General’s Report
Leslie A. Norman, Managing Editor, Ofice on Smoking
and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Gayle C. Windham, Ph.D., M.S.P.H., Research Scientist
Supervisor, Chief, Environmental Surveillance Unit, Division of Environmental and Occupational Disease Control,
California Department of Public Health, Richmond, California.
Anne McCarthy, Technical Editor, Northrop Grumman
supporting National Center for Health Marketing, Division of Creative Services, Centers for Disease Control and
Prevention, Atlanta, Georgia.
Contributing authors were
David L. Ashley, Ph.D., Chief, Emergency Response and
Air Toxicants Branch, Division of Laboratory Sciences,
National Center for Environmental Health, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Peter L. Taylor, M.B.A., Technical Editor, Senior Editor,
Palladian Partners, Silver Spring, Maryland.
Timothy B. Baker, Ph.D., Professor of Medicine, University
of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Contributing editors were
David L. Ashley, Ph.D., Chief, Emergency Response and
Air Toxicants Branch, Division of Laboratory Sciences,
National Center for Environmental Health, Centers for
Disease Control and Prevention, Atlanta, Georgia.
Steve A. Belinsky, Ph.D., Director, Lung Cancer Program,
Senior Scientist, Lovelace Respiratory Research Institute,
Albuquerque, New Mexico.
Neal L. Benowitz, M.D., Professor of Medicine and Biopharmaceutical Sciences and Chief, Division of Clinical
Pharmacology and Experimental Therapeutics, University
of California, San Francisco, California.
Neal L. Benowitz M.D., Professor of Medicine and Biopharmaceutical Sciences and Chief, Division of Clinical
Pharmacology and Experimental Therapeutics, University
of California, San Francisco, California.
Dorothy Hatsukami, Ph.D., Forster Family Professor in
Cancer Prevention, Professor of Psychiatry, University of
Minnesota Tobacco Use Research Center, University of
Minnesota, Minneapolis, Minnesota.
Tomoku Betsuyaku, M.D., Ph.D., Associate Professor, First
Department of Medicine, Hokkaido University School of
Medicine, Sapporo, Japan.
Stephen S. Hecht, Ph.D., Wallin Professor of Cancer Prevention, Masonic Cancer Center, University of Minnesota,
Minneapolis, Minnesota.
Ann M. Bode, Ph.D., Research Professor and Associate
Director, The Hormel Institute, University of Minnesota,
Austin, Minnesota.
Jack E. Henningield, Ph.D., Vice President Research and
Health Policy, Pinney Associates, Bethesda, Maryland; and
Professor, Adjunct, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of
Medicine, Baltimore, Maryland.
Anne Burke, M.D., Assistant Professor of Medicine, Gastroenterology Division, University of Pennsylvania School
of Medicine, Philadelphia, Pennsylvania.
David M. Burns, M.D., Professor Emeritus, Department of
Family and Preventive Medicine, School of Medicine, University of California, San Diego, California.
Patricia Richter, Ph.D., DABT, Toxicologist, Ofice on
Smoking and Health, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Rebecca Buus, Ph.D., Health Scientist, Maternal and Infant
Health Branch, Division of Reproductive Health, National
Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta,
Georgia.
Jonathan M. Samet, M.D., M.S., Professor and Chairman,
Department of Epidemiology, Bloomberg School of Public
Health, The Johns Hopkins University, Baltimore, Maryland (1994–2008); and Director, USC Institute for Global
Health, and Chairman, Department of Preventive Medicine, Keck School of Medicine, University of Southern
California, Los Angeles, California (2008–present).
Laurie Chassin, Ph.D., Regents Professor of Psychology,
Psychology Department, Arizona State University, Tempe,
Arizona.
vi
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
David Christiani, M.D., M.P.H., Professor, Departments of
Environmental Health and Epidemiology, Harvard School
of Public Health, Harvard University, Boston, Massachusetts.
Zigang Dong, M.D., M.S., Dr.P.H., Professor, The Hormel
Institute, University of Minnesota, Austin, Minnesota.
Björn Eliasson, M.D., Ph.D., Associate Professor, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Pamela I. Clark, M.S.P.H., Ph.D., Research Professor,
School of Public Health, University of Maryland, College
Park, Maryland.
Lucinda England, M.D., M.S.P.H., Medical Epidemiologist,
Maternal and Infant Health Branch, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
John P. Cooke, M.D., Ph.D., Professor of Medicine, Stanford University, Stanford, California.
Adolfo Correa, M.D., Ph.D., M.P.H., Medical Oficer, Division of Birth Defects and Developmental Disabilities,
National Center on Birth Defects and Developmental
Disabilities, Centers for Disease Control and Prevention,
Atlanta, Georgia.
Reginald Fant, Ph.D., Senior Scientist and Director, Pinney Associates, Bethesda, Maryland.
Garret A. FitzGerald, M.D., Chair, Department of Pharmacology, and Director, Institute for Translational Medicine
and Therapeutics, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania.
Johannes Czernin, M.D., Professor, Molecular and Medical
Pharmacology, and Chief, Ahmanson Biological Imaging
Division, David Geffen School of Medicine, University of
California, Los Angeles, California.
Mari S. Golub, Ph.D., Staff Toxicologist, Ofice of Environmental Health Hazard Assessment, California Environmental Protection Agency, Sacramento, California.
Gerald N. DeLorenze, Ph.D., Research Scientist, Division
of Research, Kaiser Permanente Northern California, Oakland, California.
Dorothy Hatsukami, Ph.D., Forster Family Professor in
Cancer Prevention, Professor of Psychiatry, University of
Minnesota Tobacco Use Research Center, University of
Minnesota, Minneapolis, Minnesota.
David M. DeMarini, Ph.D., Genetic Toxicologist, Integrated
Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
Stephen S. Hecht, Ph.D., Wallin Professor of Cancer Prevention, Masonic Cancer Center, University of Minnesota,
Minneapolis, Minnesota.
Delia Dempsey, M.D., M.S., Assistant Professor, Pediatrics,
Medicine and Clinical Pharmacology, Division of Clinical
Pharmacology, University of California, San Francisco,
San Francisco, California.
Phillip A. Dennis, M.D., Ph.D., Senior Investigator, Medical
Oncology Branch, Center for Cancer Research, National
Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
Marc K. Hellerstein, M.D., Ph.D., Professor (DH Calloway
Chair in Human Nutrition), Department of Nutritional
Sciences, University of California, Berkeley, California;
and Professor of Endocrinology, Metabolism and Nutrition, Department of Medicine, University of California,
San Francisco, California.
Yan Shirley Ding, Ph.D., Senior Service Fellow, Emergency Response and Air Toxicants Branch, Division of
Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention,
Atlanta, Georgia.
Jack E. Henningield, Ph.D., Vice President Research and
Health Policy, Pinney Associates, Bethesda, Maryland; and
Professor, Adjunct, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of
Medicine, Baltimore, Maryland.
Mirjana V. Djordjevic, Ph.D., Program Director, Tobacco
Control Research Branch, Behavioral Research Program,
Division of Cancer Control and Population Sciences,
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland.
Brian Hitsman, Ph.D., Assistant Professor, Department of
Preventive Medicine, Northwestern University, Chicago,
Illinois.
vii
Surgeon General’s Report
James C. Hogg, M.D., Ph.D., Emeritus Professor of
Pathology and Lab Medicine, iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia and St. Paul’s Hospital, Vancouver, British
Columbia, Canada.
Raymond Niaura, Ph.D., Professor, Department of Psychiatry and Human Behavior, The Warren Alpert
Medical School of Brown University; and Director, Transdisciplinary Research, Butler Hospital, Providence, Rhode
Island.
Anne M. Joseph, M.D., M.P.H., Wexler Professor of Medicine, and Director, Applied Clinical Research Program,
University of Minnesota Medical School, Minneapolis,
Minnesota.
James Pankow, Ph.D., Professor, Department of Chemistry, and Department of Civil and Environmental Engineering, Portland State University, Portland, Oregon.
Steve Pappas, Ph.D., Research Chemist, Emergency
Response and Air Toxicants Branch, Division of Laboratory
Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Caryn Lerman, Ph.D., Mary W. Calkins Professor, Department of Psychiatry and Annenberg Public Policy Center;
and Director, Tobacco Use Research Center, Scientiic
Director, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Terry F. Pechacek, Ph.D., Associate Director for Science,
Ofice on Smoking and Health, National Center for
Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.
William MacNee, Professor, ELEGI Colt Research Labs,
MRC Centre for Inlammation Research, The Queen’s
Medical Research Institute, University of Edinburgh,
Edinburgh, Scotland, United Kingdom.
Kenneth A. Perkins, Ph.D., Professor of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Athina Markou, Ph.D., Professor, Department of Psychiatry, School of Medicine, University of California, San
Diego, La Jolla, California.
Lisa A. Peterson, Ph.D., Professor, Masonic Cancer Center
and the Division of Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota.
Robert Merritt, M.A., Branch Chief, Epidemiology and
Surveillance Branch, Division of Heart Disease and Stroke
Prevention, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Gerd P. Pfeifer, Ph.D., Professor and Chair, Division of Biology, Beckman Research Institute, City of Hope National
Medical Center, Duarte, California.
Dennis L. Molfese, Ph.D., Distinguished University Scholar
and Professor, Birth Defects Center, University of Louisville, Louisville, Kentucky.
Halit Pinar, M.D., Director, Division of Perinatal and Pediatric Pathology, Women and Infants Hospital of Rhode
Island; and Professor, Department of Pathology and Laboratory Medicine, Brown University Alpert School of Medicine, Providence, Rhode Island.
Masaaki Moriya, Ph.D., Research Professor, Laboratory of
Chemical Biology, Department of Pharmacological Sciences, University at Stony Brook, The State University of
New York, Stony Brook, New York.
Gregory Polzin, Ph.D., Research Chemist, Emergency
Response and Air Toxicants Branch, Division of Laboratory
Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Marcus Munafò, M.A., M.Sc., Ph.D., Reader in Biological
Psychology, Department of Experimental Psychology, University of Bristol, Bristol, United Kingdom.
Patricia Richter, Ph.D., DABT, Toxicologist, Ofice on
Smoking and Health, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Sharon E. Murphy, Ph.D., Professor, Biochemistry, Molecular Biology and BioPhysics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Nancy Rigotti, M.D., Professor of Medicine, Harvard Medical School; and Director, Tobacco Research and Treatment
Center, Massachusetts General Hospital, Boston, Massachusetts.
viii
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Wendie A. Robbins, Ph.D., Associate Professor, UCLA
Schools of Nursing and Public Health, University of California, Los Angeles, California.
Weija (William) Wu, Ph.D., Senior Service Fellow, Emergency Response and Air Toxicants Branch, Division of
Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention,
Atlanta, Georgia.
Andrew G. Salmon, M.A., D.Phil., Senior Toxicologist,
Ofice of Environmental Health Hazard Assessment, California Department of Health Services, Oakland, California.
Mitchell Zeller, J.D., Vice President for Policy and Strategic Communications, Pinney Associates, Bethesda, Maryland.
Jonathan M. Samet, M.D., M.S., Professor and Chairman,
Department of Epidemiology, Bloomberg School of Public
Health, The Johns Hopkins University, Baltimore, Maryland (1994–2008); and Director, USC Institute for Global
Health, and Chairman, Department of Preventive Medicine, Keck School of Medicine, University of Southern
California, Los Angeles, California (2008–present).
Reviewers were
Erik M. Augustson, Ph.D., M.P.H., Behavioral Scientist/
Psychologist, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and
Population Sciences, National Cancer Institute, National
Institutes of Health, Bethesda, Maryland.
Robert M. Senior, M.D., Professor of Pulmonary Medicine,
Cell Biology & Physiology, Division of Pulmonary and
Critical Care, Washington University School of Medicine,
St. Louis, Missouri.
Cathy L. Backinger, Ph.D., M.P.H., Chief, Tobacco Control
Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National
Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
Edwin K. Silverman, M.D., Ph.D., Associate Professor of
Medicine, Harvard Medical School, Harvard University;
and Associate Physician, Brigham and Women’s Hospital,
Boston, Massachusetts.
Neal L. Benowitz M.D., Professor of Medicine and Biopharmaceutical Sciences and Chief, Division of Clinical
Pharmacology and Experimental Therapeutics, University
of California, San Francisco, California.
Margaret R. Spitz, M.D., M.P.H., Professor and Chair,
Department of Epidemiology, The University of Texas,
M. D. Anderson Cancer Center, Houston, Texas.
Mary Beth Bigley, Dr.P.H., M.S.N., A.N.P., Acting Director of the Ofice of Science and Communication, Ofice
of the Surgeon General, Ofice of Public Health and Science, Ofice of the Secretary, U.S. Department of Health
and Human Services, Washington, D.C.
Stephen B. Stanill, M.S., Chemist, Emergency Response
and Air Toxicants Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Prudence Talbot, Ph.D., Professor of Cell Biology, Department of Cell Biology and Neuroscience, University of California, Riverside, California.
Michele Bloch, M.D., Ph.D., Medical Oficer, Tobacco Control Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National
Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
Anne Thorndike, M.D., M.P.H., Instructor in Medicine,
General Medicine Unit, Massachusetts General Hospital,
Boston, Massachusetts.
Naomi Breslau, Ph.D., Professor, Department of Epidemiology, Michigan State University, East Lansing, Michigan.
Clifford H. Watson, Ph.D., Lead Research Chemist, Emergency Response and Air Toxicants Branch, National Center for Environmental Health, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Klaus D. Brunnemann, M.S., Research Associate, New
York Medical College, Valhalla, New York.
David M. Burns, M.D., Professor Emeritus, Department of
Family and Preventive Medicine, School of Medicine, University of California, San Diego, California.
Gayle C. Windham, Ph.D., M.S.P.H., Research Scientist
Supervisor, Chief, Environmental Surveillance Unit, Division of Environmental and Occupational Disease Control,
California Department of Public Health, Richmond, California.
ix
Surgeon General’s Report
Pamela I. Clark, M.S.P.H., Ph.D., Research Professor,
School of Public Health, University of Maryland, College
Park, Maryland.
Stanton Glantz, Ph.D., Professor of Medicine, Division of
Cardiology, University of California, San Francisco, California.
Gregory N. Connolly, D.M.D., M.P.H., Professor, Department of Society, Human Development, and Health, Harvard School of Public Health, Harvard University, Boston,
Massachusetts.
Michael R. Guerin, Ph.D., Associate Division Director
(retired), Oak Ridge National Laboratory, Knoxville, Tennessee.
Dorothy Hatsukami, Ph.D., Forster Family Professor in
Cancer Prevention, Professor of Psychiatry, University of
Minnesota Tobacco Use Research Center, University of
Minnesota, Minneapolis, Minnesota.
William A. Corrigall, Ph.D., Professor of Psychiatry, University of Minnesota; and Senior Scientist, Minneapolis
Medical Research Foundation, Minneapolis, Minnesota.
James D. Crapo, M.D., Professor of Medicine, National
Jewish Health, Denver, Colorado.
Jack E. Henningield, Ph.D., Vice President Research and
Health Policy, Pinney Associates, Bethesda, Maryland; and
Professor, Adjunct, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of
Medicine, Baltimore, Maryland.
Michael Criqui, M.D., M.P.H., Professor and Chief, Division of Preventive Medicine, Department of Family and
Preventive Medicine; and Professor, Department of Medicine, School of Medicine, University of California, San
Diego, La Jolla, California.
Allison Chausmer Hoffman, Ph.D., Program Director,
National Institute on Drug Abuse, National Institutes of
Health, Bethesda, Maryland.
K. Michael Cummings, Ph.D., M.P.H., Senior Research
Scientist, Chair, Department of Health Behavior, Division
of Cancer Prevention and Population Sciences, Roswell
Park Cancer Institute, Buffalo, New York.
John R. Hoidal, M.D., Professor and Chairman of Medicine, School of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah.
Mirjana V. Djordjevic, Ph.D., Program Director, Tobacco
Control Research Branch, Behavioral Research Program,
Division of Cancer Control and Population Sciences,
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland.
John E. Hokanson, Ph.D., Associate Professor and Chair,
Department of Epidemiology, Colorado School of Public
Health, University of Colorado, Denver, Aurora, Colorado.
John Hughes, M.D., Professor, Department of Psychiatry,
University of Vermont, Burlington, Vermont.
Erik Dybing, M.D., Ph.D., Division Director and Professor
(retired), Division of Environmental Health, Norwegian
Institute of Public Health, Oslo, Norway.
Richard D. Hurt, M.D., Professor of Medicine, Mayo Clinic
College of Medicine, Rochester, Minnesota.
Michael Eriksen, Sc.D., Professor, and Director, Institute
of Public Health, Georgia State University, Atlanta, Georgia.
Jared B. Jobe, Ph.D., FABMR, Program Director, Clinical
Applications and Prevention Branch, Division of Prevention and Population Sciences, National Heart, Lung, and
Blood Institute, National Institutes of Health, Bethesda,
Maryland.
Jefferson Fowles, Ph.D., Toxicologist, LyondellBasell
Industries, Rotterdam, The Netherlands.
Rachel Kaufmann, Ph.D., M.P.H., Deputy Associate Director for Science, Ofice on Smoking and Health, National
Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta,
Georgia.
Adi F. Gazdar, M.D., Professor, Department of Pathology,
University of Texas Southwestern Medical Center, Dallas,
Texas.
Gary A. Giovino, Ph.D., M.S., Professor and Chair, Department of Health Behavior, School of Public Health and
Health Professions, University at Buffalo, The State University of New York, Buffalo, New York.
Karl T. Kelsey, M.D., M.O.H., Professor, Community
Health and Pathology and Laboratory Medicine, Director,
Center for Environmental Health and Technology, Brown
University, Providence, Rhode Island.
x
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Juliette Kendrick, M.D., Medical Officer, Division of
Reproductive Health, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Wallace Pickworth, Ph.D., Health Research Leader, Battelle Centers for Public Health Research and Evaluation,
Baltimore, Maryland.
John M. Pinney, President, Pinney Associates, Bethesda,
Maryland.
Martin Kharrazi, Ph.D., Chief, Program Research and
Demonstration Section, Genetic Disease Screening Program, California Department of Public Health, Richmond,
California.
Britt C. Reid, D.D.S., Ph.D., Chief, Modiiable Risk Factors
Branch, Epidemiology and Genetics Research Program,
Division of Cancer Control and Population Sciences,
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland.
Taline V. Khroyan, Ph.D., Behavioral Pharmacologist, SRI
International, Center for Health Sciences, Menlo Park,
California.
John E. Repine, M.D., Director, Webb-Waring Center, Waring Professor of Medicine and Pediatrics, School of Medicine, University of Colorado, Denver, Colorado.
Walther N.M. Klerx, Food and Consumer Product Safety
Authority, Eindhoven, The Netherlands.
Philip Lazarus, Ph.D., Professor of Pharmacology, College
of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, Pennsylvania.
William Rickert, Ph.D., Chief Executive Oficer, Labstat
International ULC, Kitchener, Ontario, Canada.
David J. Riley, M.D., Professor, Department of Medicine,
University of Medicine and Dentistry of New Jersey, Robert
Wood Johnson Medical School, Piscataway, New Jersey.
Scott Leischow, Ph.D., Associate Director for Behavioral
and Social Sciences Research, Arizona Cancer Center, The
University of Arizona, Tucson, Arizona.
Scott Rogers, M.P.H., Public Health Advisor, Epidemiology
and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland.
Christina N. Lessov-Schlaggar, Ph.D., Research Assistant
Professor, Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
Catherine Lorraine, Director, Policy Development and
Coordination Staff, Food and Drug Administration, Silver
Spring, Maryland.
Dale P. Sandler, Ph.D., Chief, Epidemiology Branch,
National Institute of Environmental Health Sciences,
National Institutes of Health, Research Triangle Park,
North Carolina.
Cathy Melvin, Ph.D., M.P.H., Director, Child Health Services Program, Cecil G. Sheps Center for Health Services
Research, University of North Carolina, Chapel Hill, North
Carolina.
David A. Scott, Ph.D., Associate Professor, Oral Health and
Systemic Disease Research Group, University of Louisville, Louisville, Kentucky.
John D. Minna, M.D., Director, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.
Harold E. Seifried, Ph.D., DABT, Chemist, Toxicologist,
Industrial Hygienist (retired), Program Director, Nutritional Sciences Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland.
Joshua E. Muscat, Ph.D., Professor, Department of Public
Health Sciences, College of Medicine, Pennsylvania State
University, Milton S. Hershey Medical Center, Hershey,
Pennsylvania.
Peter G. Shields, M.D., Professor of Medicine and Oncology, Deputy Director, Lombardi Comprehensive Cancer
Center, Georgetown University Medical Center, Washington, D.C.
Mark Parascandola, Ph.D., M.P.H., Epidemiologist,
Tobacco Control Research Branch, Behavioral Research
Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland.
Saul Shiffman, Ph.D., Research Professor, Psychology and
Psychiatry, University of Pittsburgh; and Senior Scientiic
Advisor, Pinney Associates, Pittsburgh, Pennsylvania.
xi
Surgeon General’s Report
Donald R. Shopland, Sr., U.S. Public Health Service
(retired), Ringgold, Georgia.
Other contributors were
Charlotte Gerczak, M.L.A., Communications Associate,
Department of Epidemiology, Bloomberg School of Public
Health, The Johns Hopkins University, Baltimore, Maryland.
Stephen Sidney, M.D., M.P.H., Associate Director for Clinical Research, Division of Research, Kaiser Permanente,
Oakland, California.
Roberta B. Gray, Administrative Supervisor to Dr. Jonathan M. Samet, Department of Epidemiology, Bloomberg
School of Public Health, The Johns Hopkins University,
Baltimore, Maryland.
Gary D. Stoner, Ph.D., Professor Emeritus, Department of
Internal Medicine, The Ohio State University, Columbus,
Ohio.
Gary E. Swan, Ph.D., Director, Center for Health Sciences,
SRI International Fellow, SRI International, Center for
Health Sciences, Menlo Park, California.
Marta Gwinn, M.D., M.P.H., Medical Oficer, Ofice of Public Health Genomics, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease
Control and Prevention, Atlanta, Georgia.
Michael J. Thun, M.D., M.S., Vice President Emeritus, Epidemiology and Surveillance Research, American Cancer
Society, Atlanta, Georgia.
Nancy Leonard, Administrative Coordinator to Dr. Jonathan M. Samet, Department of Epidemiology, Bloomberg
School of Public Health, The Johns Hopkins University,
Baltimore, Maryland.
Robert B. Wallace, M.D., M.Sc., Irene Ensminger Stecher
Professor of Epidemiology and Internal Medicine, Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa.
Deborah Williams, Desktop Publishing Specialist to Dr.
Jonathan M. Samet, Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Deborah M. Winn, Ph.D., Deputy Director, Epidemiology
and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland.
xii
How Tobacco Smoke Causes Disease: The Biology and
Behavioral Basis for Smoking-Attributable Disease
Chapter 1.
Introduction, Evaluation of Evidence on Mechanisms of Disease Production, and Summary 1
Introduction 3
Evaluation of Evidence on Mechanisms of Disease Production 5
Mechanisms of Action: Necessary, Suficient, or Neither 7
Description of Evidence on Mechanisms of Disease Production 8
Scientiic Basis of the Report 8
Development of the Report 8
Major Conclusions 9
Chapter Conclusions 9
References 12
Chapter 2.
The Changing Cigarette 13
Introduction 15
Cigarette Design Changes over the Years 15
New Cigarette Products 17
Low-Nicotine Cigarettes 18
Cigarette-Like Products 18
Evaluation of New Cigarette Products 19
New Oversight of Tobacco Products 20
Summary 20
Conclusions 21
References 22
Chapter 3.
Chemistry and Toxicology of Cigarette Smoke and Biomarkers of Exposure and Harm 27
Introduction 29
Chemistry 30
Biomarkers 51
Summary 77
Conclusions 79
References 80
Chapter 4.
Nicotine Addiction: Past and Present 103
Introduction 105
Deinition of Nicotine Addiction 105
Tobacco Constituents and Pharmacokinetics 111
Components of Nicotine Addiction 116
Pathophysiology of Nicotine Addiction 124
Genetics 137
Prevalence and Trajectory Toward Nicotine Dependence 156
Epidemiology of Tobacco Use and Nicotine Dependence in Adults 162
Trajectory of Recovery or Relapse 170
xiii
Evidence Summary 180
Conclusions 183
References 184
Chapter 5.
Cancer 221
Introduction 225
Carcinogen Exposure, Metabolism, and DNA Adducts 227
DNA Repair and Conversion of Adducts to Mutations 252
Gene Mutations in Tobacco-Induced Cancer 274
Loss of Mechanisms for Growth Control 284
Other Aspects 296
Evidence Summary 302
Conclusions 304
References 305
Chapter 6.
Cardiovascular Diseases 351
Introduction 355
Tobacco Use and Cardiovascular Disease 355
Secondhand Tobacco Smoke and Cardiovascular Disease 363
Pathophysiology 363
Hemodynamic Effects 368
Smoking and the Endothelium 370
Thrombogenic Effects 374
Inlammation 382
Smoking and Diabetes 383
Lipid Abnormalities 387
Cardiovascular Biomarkers 391
Smoking Cessation and Cardiovascular Disease 394
Methods to Reduce Exposure 402
Evidence Summary 407
Conclusions 408
References 409
Chapter 7.
Pulmonary Diseases 435
Introduction 437
Smoking and Respiratory Defense Mechanisms 450
Oxidative Stress 457
Oxidative Stress in Chronic Obstructive Pulmonary Disease 471
Genetics of Pulmonary Disease and Susceptibility to Tobacco Smoke 475
Pathogenesis of Emphysema 487
Summary 494
Evidence Summary 494
Conclusions 496
Implications 496
References 497
Chapter 8.
Reproductive and Developmental Effects 521
Introduction 523
xiv
Review of Epidemiologic Literature on Smoking 524
Pathophysiological and Cellular and Molecular Mechanisms of Smoking 555
Implications 606
Evidence Summary 608
Conclusions 612
References 613
Chapter 9.
A Vision for the Future 645
The Global Tobacco Epidemic 647
Reducing the Risks from Smoking 651
Ending the Tobacco Epidemic 652
Concluding Remarks 654
Appendix 9.1: Recommendations for Future Research 655
Appendix 9.2: Ending the Tobacco Problem: A Blueprint for the Nation 660
Appendix 9.3: Promoting Healthy Lifestyles: Policy, Program, and Personal Recommendations for
Reducing Cancer Risk 664
References 667
List of Abbreviations
671
List of Tables and Figures
675
Deinitions and Alternative Nomenclature of Genetic Symbols Used in This Report 679
Index
689
xv
Chapter 1
Introduction, Evaluation of Evidence on
Mechanisms of Disease Production, and Summary
Introduction 3
Evaluation of Evidence on Mechanisms of Disease Production 5
Mechanisms of Action: Necessary, Suficient, or Neither 7
Description of Evidence on Mechanisms of Disease Production 8
Scientiic Basis of the Report 8
Development of the Report 8
Major Conclusions
9
Chapter Conclusions 9
Chapter 2. The Changing Cigarette 9
Chapter 3. Chemistry and Toxicology of Cigarette Smoke and Biomarkers of Exposure and Harm 9
Chapter 4. Nicotine Addiction: Past and Present 10
Chapter 5. Cancer 10
Chapter 6. Cardiovascular Diseases 10
Chapter 7. Pulmonary Diseases 11
Chapter 8. Reproductive and Developmental Effects 11
References
12
1
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease
Introduction
Since the irst of the series in 19