Preface Humans are continuously exposed to carcinogens from environmental, occupational, and endogenous sources. Health professionals, regulatory agencies, and cancer researchers are frequently challenged to identify the causes of cancer, to predict risks, and to develop methods to prevent cancer. The assessment of cancer risk in individuals or the population is a complex process that reflects both actual science and scientific intuition. There is an exploding amount of information-in many cases conflicting information- and a confusing array of sources to consider about the applicability and use of biomarkers. New data from the Human Genome Project, the latest technologies in molecular genetics (e.g., proteomics, microarrays, high-throughput assay methods), are rapidly being incorporated into risk assessment and epidemiological studies, and there are many challenges to the interpretation of the resulting data. Clearly, the use of biomarkers and genetic susceptibility analysis is improving our ability to predict risk in the population and the individual, but it is a rapidly evolving and complicated area of research. Students of molecular epidemiology and people outside of the field need guidance to use and interpret biomarker data, and a context from to evaluate whether the data improve the risk assessment process.
This book is intended for health professionals, public health specialists, persons within regulatory agencies, and cancer researchers who need more than a summary of recent data. It provides a practical approach to conducting risk assessment for the population and the individual in the context of biomarkers and genetic susceptibilities, especially within a broader perspective of background cancer risk and an individual’s exposures within a complex environment. While the risk assessment process usually focuses on a single particular exposure, people are constantly exposed to a multitude of known and potential human carcinogens-from the air, their diet and lifestyle, etc. When setting public health priorities or evaluating a person with cancer, this broader context makes the risk assessment process much more challenging. This text helps the reader place cancer risk within such a context, and understand the relative risks from different exposures and how biomarkers and genetic susceptibilities help in the risk assessment process.
Biomarkers are tests conducted on any biological tissue or fluid, including air. Assays to assess an individual’s risk through specific genes, thereby assessing genetic susceptibilities, also are a type of biomarker. However, the term biomarker usually refers to an assay of exposure, biologically effective dose, or some effect of exposure. The term genetic susceptibility refers to an individual’s heritable capacity to respond to exposures, which would therefore result in modifying cancer risk. Biomarkers can be used as intermediate markers of cancer risk, reflecting a mechanistic pathway to cancer. Genetic susceptibilities would therefore affect the level of biomarkers, reflecting a gene-environment interaction. Therefore, the term geneenvironment interaction refers to an effect of exposure that is increased or decreased by genetic susceptibilities; it is used generically and there are formal statistical methods to assess interactions. Most cancers are considered to be caused by carcinogenic exposures, although with most cancers and therefore in most people, the causes have not been identified. Although the body has the capacity to repair much of the damage from gene-environment interactions, it is the sheer number of gene-environment interactions that actually contribute to the carcinogenic process. Biomarkers now are enhancing our understanding about the causes of cancer, and in some cases are helping identify what specifically caused a cancer in a particular person.
The use of biomarkers is not new and has been around for more than 50 years. But the last 20 years have seen rapidly developing technologies, which recently have greatly accelerated. These newer methods bring analytical and bioinformatic challenges but nonetheless show great promise for enhancing our risk assessment processes further.
Frequently the public and individuals with cancer make conclusions about the causes of cancer that are not founded upon sound data or based on appropriate assessment methodologies. The public health community is obligated to understand and communicate the latest scientific data in the context of the risk assessment process for the general population, persons at high risk, and individuals within the general population. This text provides the reader with the tools to assess cancer causation with specific methodologies, rather than relying on intuition and speculation.
Cancer is a multistage process that is triggered by multiple steps through many pathways. There are many repair and protective mechanisms in the human body to prevent most DNA damage that would otherwise lead to cancer. Typically, the determination of a cancer risk factor requires the examination of a potential etiological agent against a background of many real etiological agents. Many new laboratory and epidemiological findings are impacting how we think about cancer risk, while many principles used in the assessment of causation remain conceptually important. This book presents recent data that impact cancer risk for the general population and individual, and reviews data for some known and potential human carcinogens. It reviews the methods for determining what causes cancer and what does not. Practical approaches to the determination of cancer risk in individuals and the population are offered, including counseling of individuals, groups of exposed persons, and society as a whole.
This text is organized to provide the most current information in two ways. The first approaches risk assessment from a methodological perspective. The reader is provided information about carcinogenesis in general and then specifically for chemical, radiation, viral, occupational, and familial cancers. While there is overlap in some of these mechanisms (e.g., chemical and occupational carcinogenesis), there are different mechanistic approaches to consider depending on the perspective. One particular focus includes recent data for tobacco, alcohol, and hormonal mechanisms in cancer risk, as these are among the major known human carcinogens and carcinogenic mechanisms. Additionally, how people are exposed to known and suspected carcinogens is identified, with particulars on how to measure this in the workplace using industrial hygiene methods. Information about differences in cancer risk among various ethnic and racial populations in the context of different exposures and mechanistic etiologies are also discussed.
The second methodology includes basic epidemiological approaches as they apply to molecular epidemiology, including both the use of biomarkers and genetics within an epidemiological framework. Detailed approaches in the use of genetic testing for cancer risk, using both markers in cancers and then measures of genetic damage in persons without cancer, are given. The actual approach to risk assessment is highlighted in detail in three separate chapters. The readers are provided with the distinct approaches to population and individual risk assessment, and also with information about how regulatory agencies determine what is a carcinogen. The chapter on individual risk assessment is particularly unique as the reader is provided with a framework for evaluating an individual who has cancer, or is thought to be at risk for cancer.
The second half of the text provides the reader with cancer risk information by organ system for major cancers. It uses the principals established in the first part of the text, which provided the reader with the tools to evaluate risk, and applies them to single organ sites. While this text provides a summary of the latest data for biomarkers and genetic susceptibilities within the risk assessment process, it cannot provide a critique of all available data. However, it will equip the reader to explore and assess further data.
The production of this text required the hard work of many people, and I would like to thank my co-authors and contributors specifically for their patience and multiple iterations to produce what are outstanding chapters. I also will like to thank Sandi Crawford and Regina Jackson for the expert organizational assistance, without which this book would never have been completed.
Peter G. Shields Contributors
Christine B. Ambrosone Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York, U.S.A.
Melissa L. Bondy Department of Epidemiology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
Anne-Lise Burresen-Dale Department of Genetics, Institute for Cancer Research, University Clinic of the Norwegian Radium Hospital, Oslo, Norway Diane L. Carlisle Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
James R. Cerhan Health Sciences Research, Mayo Clinic College of Medicine, Rochester, New York, U.S.A.
Susan S. Devesa Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, U.S.A.
Mustafa Dosemeci Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, U.S.A.
Randa El-Zein Department of Epidemiology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
Heather Spencer Feigelson Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia, U.S.A.
Christina Frank Department of Epidemiology, University of Maryland School of Medicine, Baltimore, Maryland, U.S.A.
Helena Furberg Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, U.S.A.
Laura Gunn Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, California, U.S.A.
Pierre Hainaut International Agency for Research on Cancer, Lyon, France Aage Haugen Department of Toxicology, National Institute of Occupational Health, Oslo, Norway Richard B. Hayes Division of Cancer Epidemiology and Genetics,
National Cancer Institute, DHHS, Bethesda, Maryland, U.S.A.
Kathy J. Helzlsouer Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, U.S.A., and Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, U.S.A.
Michie Hisada Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, U.S.A.
Carrie P. Hunter North Potomac, Martland, U.S.A.
Alan M. Jeffrey Department of Pathology, New York Medical College, Valhalla, New York, U.S.A.
Charles E. Land Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland,
Loic Le Marchand Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, U.S.A.
Martha S. Linet Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, U.S.A.
Christopher Loffredo Cancer Genetics and Epidemiology Program,
Department of Oncology, Georgetown University School of Medicine, Washington, D.C., U.S.A.
Ragnhild A. Lothe Department of Genetics, Institute for Cancer Research, University Clinic of the Norwegian Radium Hospital, Oslo, Norway Robert J. McCunney Department of Biological Engineering, Massachusetts Institute of Technology, Pulmonary Division, Massachusetts General Hospital, Boston, Massachusetts, U.S.A.
Roberta McKean-Cowdin Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California, U.S.A.
Yuri Minn Department of Epidemiology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
Ruggero Montesano International Agency for Research on Cancer, Lyon, France Gareth J. Morgan Department of Hematology, Institute of Pathology, University of Leeds, Leeds, U.K.
Kirsten B. Moysich Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York, U.S.A.
Lee Okurowski Department of Orthopedics, Occupational Health, New England Baptist Hospital, Boston, Massachusetts, U.S.A.
Steven R. Patierno Department of Pharmacology, George Washington University, Washington, D.C., U.S.A.
Charles S. Rabkin Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, U.S.A.
Jerry M. Rice Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., U.S.A.
Hongbing Shen Department of Epidemiology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
Peter G. Shields Cancer Genetics and Epidemiology Program, Department of Medicine and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, U.S.A.
Martyn T. Smith Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, California, U.S.A.
Margaret R. Spitz Department of Epidemiology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
Erich M. Sturgis Department of Head and Neck Surgery, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
Haruhiko Sugimura Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan Philippe Taniere International Agency for Research on Cancer, Lyon, France Paolo Vineis Unit of Cancer Epidemiology and Chair of Biostatistics, Dipartimento di Scienze Biomediche e Oncologia Umana, University of Turim, Turim, Italy Kala Visvanathan Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, U.S.A.
Elizabeth Ward Industrywide Studies Branch Division of Surveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, Cincinnati, Ohio, U.S.A.
Qingyi Wei Department of Epidemiology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
John Whysner Washington Occupational Health Associates, Washington, D.C., U.S.A.
Gary M. Williams Department of Pathology, New York Medical College, Valhalla, New York, U.S.A.
Margaret Wrensch Department of Epidemiology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas, U.S.A.
Luoping Zhang Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, California, U.S.A.