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· - - - ~· Al Medical Follow-up Agency INSTITUTE OF MEDICINE by Susan Thrum, William F. Page, Harriet Crawford, and Heather O'Maonaigh with oversight from the Committee to Study the Mortality of Military Personnel Present at Atmospheric Tests of Nuclear Weapons NATIONAL ACADEMY PRESS Washington, D.C.

NATIONAL ACADEMY PRESS · 2101 Constitution Avenue, N.W. · Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Insti- tute of Medicine. The members of the advisory committee for the report were chosen for their special competences and with regard for appropriate balance. Support for this project was provided by the Defense Threat Reduction Agency, formerly the Defense Nuclear Agency (DNA), under Contract No. DNA001-92-C-0042. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Defense Threat Reduction Agency position, policy, or decision unless so designated by other documentation. International Standard Book Number 0-309-06781-2 Additional copies of this report are available for sale from the National Academy Press, 2101 Constitution Avenue, N.W., Box 285, Washington, DC 20055. Call (800) 624-6242 or (202) 334-3313 in the Washington metropolitan area), or visit the NAP on- line bookstore at www.nap.edu. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2000 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

it: A: National Academy of Sciences National Academy of Engineering Institute of Medicine National Research Council The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the re- sponsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the Na- tional Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council. . . .

AUTHORS, INSTITUTE OF MEDICINE SUSAN THAUL (Study Director), Epidemiologist WILLIAM F. PAGE, Statistician HARRIET CRAWFORD, Operations Director HEATHER O'MAONAIGH, Research Associate ADVISORY COMMITTEE TO STUDY THE MORTALITY OF MILITARY PERSONNEL PRESENT AT ATMOSPHERIC TESTS OF NUCLEAR WEAPONS Current Advisory Committee HARVEY CHECKOWAY (Chair), Professor, Departments of Environmental Health and Epidemiology, University of Washington, Seattle RICHARD J. M. FRY, Consultant, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee SAMUEL HELLMAN, A.N. Pritzker Distinguished Service Professor, Department of Radiation and Cellular Oncology, The University of Chicago ELAINE RON, Chief, Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland WILLIAM G. SEIBERT, Senior Archivist, National Personnel Records Center, St. Louis, Missouri JOHN E. TILL, President, Risk Assessment Corporation, Neeses, South Carolina CLARICE R. WEINBERG, Chief, Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina Former Members of Advisory Committee CLARK W. HEATH, JR. (until 2/lS/99) DAVID HOEL (until 12/l/94) JOHN LITTLE (until 319194) RODNEY WITHERS (until 819194)

WORKING GROUP ON DOSIMETRY JOHN E. TILL (Chair), committee member F. OWEN HOFFMAN, SENES of Oak Ridge, Inc. KEITH J. SCHIAGER, Department of Radiological Health, University of Utah, Salt Lake City JOHN TASCHNER, Los Alamos National Laboratory, New Mexico CLARICE R. WEINBERG, committee member MEDICAL FOLLOW-UP AGENCY RICHARD N. MILLER, Director PAMELA RAMEY-McCRAY, Administrative Assistant Not a member of the advisory committee. V1

REVIEWERS This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures ap- proved by the National Research Council's Report Review Committee. The pur- pose of this independent review is to provide candid and critical comments that will assist the Institute of Medicine in making the published report as sound as possible and to ensure that the report meets institutional standards for objectiv- ity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. The committee wishes to thank the following individuals for their par- ticipation in the review of this report: JOHN D. BOICE, JR., International Epidemiology Institute, Rockville, Maryland DAVID BRENNER, Center for Radiological Research, Columbia University School of Public Health, New York ETHEL S. GILBERT, Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland MAUREEN M. HENDERSON, Department of Epidemiology, University of Washington, Seattle MATTHEW PUGLISI, The American Legion, Washington, D.C. JONATHAN M. SAMET, Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland RICHARD B. SETLOW, Brookhaven National Laboratory, Upton, New York Although the individuals listed above have provided constructive comments and suggestions, it must be emphasized that responsibility for the final content of this report rests entirely with the authors and the Institute of Medicine. ; V11

Preface For more than half a century, veterans, scientists, and the public have de- bated and searched for answers about whether military personnel involved in nuclear tests experienced adverse health effects because of their participation. The study we report here is the latest attempt to quantify and understand the aftermath of those tests. Throughout the Five Series Study, the Medical Follow-up Agency staff has relied on the guidance of the Institute of Medicine advisory committee created to oversee the study. Members included leading experts in radiation and cancer epidemiology, biostatistics, radiation biology and medicine, radiation physics and dosimetry, and national archival sources. The committee provided informa- tion, leads, insight, and technical assistance and the report is better for that inter- action, but responsibility for the final product rests with the staff. This report presents the information that we could derive from this study. How scientists, the government, veterans, and the general public interpret and use that information is now open for discussion but not within the scope of this study. Susan Thaul, Ph.D. William F. Page, Ph.D. Harriet Crawford, B.S. Heather O'Maonaigh, M.A. 1X

Acknowledgments The study of the five series participants has been underway in some form or another since 1982. The list of people who deserve recognition for their contri- butions is enormous. The initial study team that began the current Five Series Study was led by Dennis Robinette, a radiation biologist who died shortly before the contract to do this study was signed. His earlier report, coauthored with Seymour Jablon and Thomas Preston, set the stage for this study. Members of the data operations staff who worked through almost the entire life of the study were Chiquita "Squeaky" Benson, Mary Juman, and Sylvia McGinnis, joined in recent years by Jihad Daghmash. Others who worked on the data collection and management for this project include Phillip Bailey, Noah Dropkin, Nicholas Findlay, Faye Lucas, Jean Philemond, Elaine Pickens, Alex Saenger, and Denise Tyner-Parker. Erin Bell, Christopher Howson, Philip Ren- zullo, and Youn Shim each worked on the epidemiology of this study. Christo- pher Johnson, to whom this report is dedicated, was the project director and source of radiation and health physics and military radiation safety operations information for the most of the study period. The data collection efforts for the Five Series Study involved a cast of hun- dreds. We appreciate the efforts of Robert Bilgrad and staff at the National Death Index; Clifford Amsler, Barbara Bauman, and staff at the National Per- sonnel Records Center in St. Louis, Missouri; and staff at many federal archives centers and VA regional offices across the country, especially the VA regional office in the District of Columbia. We relied on a few consultants external to the staff for some technical work critical to the conduct of the study: Charles Alcorn, Gary Marsh, Jeanette Peter- son, Florence Poillon, Karl Wise, and Ada Youk. Jeremy Yu assisted during a summer internship. X1

~ . X11 A CKWO WLEDGMENTS The MFUA staff has benefited from the vigilance and enthusiasm of many interested veterans, especially Pat Broudy; Boley Caldwell, who provided the NAAV medical survey data used in participant validation; Robert Campbell; and Oscar Rosen. The current members of the advisory committee to the Five Series Study- chair Harvey Checkoway, Richard J.M. Fry, Samuel Hellman, Elaine Ron, Wil- liam Seibert, John Till, and Clarice Weinberg have helped to ensure the qual- ity of the logic followed in the conduct of this study. We thank them and assume responsibility for whatever items of advice they offered that we did not take. The committee's report to the sponsor concerning the utility for this study of the Nuclear Test Personnel Review program dose data dosimetry included contribu- tions from invited experts not members of the committee: F. Owen Hoffman, Keith Schiager, and John Taschner. Clark Heath, Jr., David Hoel, John Little, and Rodney Withers each served as members of the advisory committee, though not to study completion. D. Michael Schaeffer has been able to convey urgency and patience simul- taneously in managing the Defense Threat Reduction Agency contract with the Institute of Medicine for this project. We thank him, Joan Ma Pierre, and the DTRA staff and contractor team, including Paul Chase and Hilda Maier of JAYCOR and Jeff Klemm of SAIC. Sue Barron, Claudia Carl, Andrea Cohen, Mike Edington, Cheryl Green- house, James Jensen, Linda Kilroy, Sandra McDermin, Barbara Rice, Catherine Stryker, Kirsten Sampson Snyder, Neil Tickner, and the many other staff at the Institute of Medicine or the National Research Council all helped along the way. Special thanks to Medical Follow-up Agency director Richard Miller and ad- ministrative assistant Pamela Ramey-McCray who provided much appreciated support to the project. We Susan Thaul, William Page, Harriet Crawford, and Heather O'Mao- naigh-thank everyone on this list (and perhaps a few whose names we have un- intentionally omitted) for producing with us this Five Series Study report.

Abbreviations, Acronyms' and Glossary a priori. A hypothesis held prior to the conduct of analysis. AEC. Atomic Energy Commission. all-cancer mortality. All deaths attributed to any malignant neoplasm. all-cause mortality. All deaths. annual dose limit. Maximum radiation dose allowed on an annual basis. ascertainment. Completeness of discovery. associated causes of death. Conditions noted on the death certificate as con tributing to an individual's death but not noted as its underlying cause. association. An observed relationship between variables; not necessarily in dicative of causation. atmospheric testing. Detonating a nuclear weapon or device in the atmosphere or close to the earth's surface as part of the testing program. U.S. testing was carried out by the Atomic Energy Commission (AEC) and supported by the Department of Defense from 1945 to 1962 (JAYCOR, 19974. atomic bomb. A term sometimes applied to a nuclear weapon using fission energy only (Bruce-Henderson, 1982~. atomic veteran. Veteran of the armed forces (here, Army, Navy, Air Force, or Marine Corps) present at one or more nuclear weapons tests. badged dose. An estimate of an individual's radiation dose as derived from one or more film badges assigned to the individual at the time of exposure. BEIR. Biological Effects of Ionizing Radiation; a series of reports by commit tees of the National Research Council, National Academy of Sciences. BEIR V. Fifth report on the Biological Effects of Ionizing Radiation (National Research Council, 1990~. bias. Systematic deviation of results or inferences from the truth, or the proc esses leading to such deviation (Last, 1995~. . . . x~

XIV ABBREVIATIONS, ACRONYMS, AND GLOSSARY BIRLS. Beneficiary Identification and Records Locator Subsystem, Depart- ment of Veterans Affairs. Electronic file of all claims; begun in 1972. branch of service. Branch of the U.S. armed forces of which an individual was ' a member at the time of nuclear weapons test participation. by-products. A secondary result, here pertaining to a nuclear reaction. cancer. A malignant tumor. CASTLE. Military code name of atmospheric test of nuclear weapons, 1954, Bikini and Enewetak Atolls, Marshall Islands, Pacific Proving Ground. causal judgment. Process used to weigh pieces of evidence including strength of association, consistency across studies, statistical significance, biologic coherence in judging whether one event or condition might be the cause of an observed outcome. cause of death. Condition indicated on an individual's death certificate as the underlying cause of death. CD C. Centers for Disease Control and Prevention, DHHS. censoring. Loss or removal of subjects from a study; observations with un- known values from one end of a frequency distribution, occurring beyond a measurement threshold (Last, 1995~. CFR. See Code of Federal Regulations. chi-square (%2) tests. Tests of statistical significance used to assess the likeli- hood that an observed bivariate relationship differs significantly from that which easily could have occurred by chance (Singleton et al., 1993~. CI. See confidence interval. claims folder. Department of Veterans Affairs administrative paper record containing information to document the process 'of a veteran's claim for benefits; maintained in the VA regional office covering the geographic re- gion of the claimant; record is retired to a federal archive records center. CLL. Chronic lymphoid leukemia,' a form of leukemia that has not been found in studies to be radiogenic. Also called chronic Iymphocytic leukemia. CNS. Central nervous system. Code of Federal Regulations (9CFRJ. A codification of the general and perma- nent rules published in the Federal Register by the executive departments and agencies of the federal government, online and as paper editions via the Government Printing Office. cohort. A group of persons defined by a shared experience, such as an expo sure. cohort study. An epidemiologic investigation involving the follow-up of one or more groups of individuals who are known to have had an exposure or a disease and whose health status is followed over time. Can usually provide a basis for calculating risk or disease outcome. comparison group. A group selected to have specific characteristics in com- mon with the study group, but which has not experienced the exposure of interest.

ABBREVIATIONS, ACRONYMS, ANT) GLOSSARY XV confidence interval (CU. Used in epidemiology/statistics. States the lower and upper bounds of the statistical precision of an estimate. confounder. A variable that is associated with the outcome under study and with exposure in the study population, but is which not a consequence of this exposure. covariate adjustment. A process by which a statistical estimate is calculated so that the effects of other covarying factors (covariates) have been accounted for. Cox proportional hazard ratio analysis. A statistical model in survival analysis asserting that the effect of the study factors on the risk of occurrence of an event in the study population is multiplicative and does not change over time (Last, 1995~. CROSSROADS. Military code name of atmospheric test of nuclear weapons, 1946, Bikini Atoll, Marshall Islands. crude death rate. A measure of the proportion of the population that dies within a specified period (Last, 1995~. The number of deaths in the popula- tion divided by the total population. Called "crude" because it does not ad- just for age or other characteristics of the population. custom dose estimates. An individual-level dose reconstruction. database. An organized set of data or collection of files that can be used for a specified purpose (Last, 19954. death certificate. A vital statistics record signed by a licensed physician or by another designated health worker that includes cause of death, decedent's name, sex, birth date, places of residence and of death, and whether the de- ceased had been medically attended before death (Last, 19954. Maintained by each state. deck logs. The documents that record the daily activities of Navy and Coast Guard ships, including a listing of officers on board (JAYCOR, 1995~. Defense Nuclear Agency ('D1VA). The name was changed to Defense Special Weapons Agency (DSWA) in 1996 and to Defense Threat Reduction Agency (DTRA) in 1998. Defense Special Weapons Agency (DSWA). New name for DNA as of 1996; changed to Defense Threat Reduction Agency (DTRA) in 1998. Defense Threat Reduction Agency (DTRA>. New name for DSWA as of 1998; earlier names were Defense Special Weapons Agency and Defense Nuclear Agency. descriptive analyses. Quantitative comparisons designed to describe the exist- ing distribution of variables without immediate regard to cause or other hy potheses. deterministic effects. Acute radiation effects, often due to cell killing; for exam- ple, burns and nausea. DHHS. Department of Health and Human Services, U.S. diagnosis codes. International Classification of Disease codes that associate a unique code number to standard cause-of-death definitions.

XVI ABBREVIATIONS, ACRONYMS, AND GLOSSARY diagnostic radiology. The medical use of radiation as a means of investigating and diagnosing disease. differential. Showing a difference, usually used in a context where a difference can produce bias. Disagreement or divergence between facts or claims. discrepancy. DNA. See Defense Nuclear Agency. DoD. Department of Defense, U.S. dose. A measurement of the biological effect of radiation on the human body; referred to as dose equivalent and measured in sievert (rem) (JAYCOR, 1997). dose reconstruction. A scientific analysis of the radiological aspects of an en vironment in space and time, used to calculate radiation levels from which an estimate of dose is made of the dose to an individual in that environment (JAYCOR, 19974. dosimetry. The measurement and recording of radiation doses and dose rates (Bruce-Henderson, 1982~. As used in the NTPR program, this term applies only to doses obtained from dosimeters (JAYCOR, 1997~. Dose-response relationship. A relationship in which a change in amount, in tensity, or duration of exposure is associated with a change in the rate or amount of a specific outcome (Last, 1995~. DSWA. See Defense Special Weapons Agency. DTRA. See Defense Threat Reduction Agency. E1-E7. Enlisted personnel paygrades. elevated risk. Risk that is elevated relative to that observed in a comparison population. endpoints. Outcomes. Here, death or death due to a specific cause. Enewetak. Atoll in the northwestern Marshall Islands in the Pacific Ocean. epidemiology. The study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control health problems (Last, 1995~. estimate. A measure or statement about the value of some quantity that is said to be an estimate if it is known, believed, or suspected to incorporate some degree of error (Last, 1995~. excess mortality. The amount by which the number of deaths observed in a group exceeds the number expected absent the exposure of interest. expected mortality. A baseline standard of mortality that would be expected absent the exposure under study; can be calculated from standard popula tion rates or from an unexposed comparison population. exposure (radiations. A term describing the amount of ionizing radiation that is incident upon living or inanimate material. exposure surrogates. Proxy measures used in instances in which the actual exposure of interest cannot be reliably assessed.

ABBREVIATIONS, ACRONYMS, AND GLOSSARY . . XV11 fact of death. Ascertainment of vital status (whether an individual is alive or dead) without respect to cause. fallout. Material (mostly radioactive) lofted into a nuclear cloud and later de- posited over an area (JAYCOR, 19974. FARC. Federal archives records center; repository of retired government rec- ords such as VA claims folders. film badge. Photographic film shielded from light and worn by an individual to measure and record radiation dose. follow-on studies. Future research endeavors warranted or proposed based on study results. follow-up period. The period of time during which observations are made of an individual, group, or initially defined population whose appropriate charac- teristics have been assessed in order to observe changes in health status or health-related variables (Last, 1995~. GAO. See General Accounting Office. General Accounting Office (GA OF. The General Accounting Office is the in- vestigative arm of Congress. Charged with examining matters relating to the receipt and disbursement of public funds, GAO performs audits and evalua- tions of government programs and activities. grade. A classification of military rank into categories. GREENHOUSE. Military code name of atmospheric test of nuclear weapons, 1951, Enewetak Atoll, Marshall Islands. ground zero. The point on the surface of land or water at, or vertically below or above, the center of the burst of a nuclear weapon Bruce-Henderson 1982). . hazard ratio (HRJ. The probability of the occurrence of an event for an indi- vidual in a study population divided by the probability of the occurrence of an event in a comparison population. HCFA. Health Care Financing Administration, DHHS. healthy soldier effect. The observed tendency of soldiers, as an aggregated group, to be in better health than the general United States population be- cause of pre-induction selection and continuing military health and per- formance standards. healthy worker effect. The observed tendency of workers, as an aggregated group, to be in better health than the general United States population. hematologic cancers. Cancers of the blood-forming organs, including the leu- kemias, Hodgkin's disease, non-Hodgkin's lymphoma, and other lympho . . po1et1c cancers. HR. See hazard ratio. ICD9. International Classification of Diseases, gth revision. (See References: USDHHS, 1991) ICRP. International Commission on Radiological Protection.

XV111 ABBREVIATIONS, ACRONYMS, AND GLOSSARY incidence. The number of persons who have developed a disease in a given period of time divided by the total population at risk. IOM. Institute of Medicine. ionizing radiation. Radiation that produces ion pairs along its path through a substance. JAYCOR. A company providing contract services to the Defense Threat Re- duction Agency; involved with the Nuclear Test Personnel Review pro- gram. ~.,, kiloton (kt9. 1,000 tons. known dead. Identified as deceased as the result of records investigation. kt. See kiloton. land series. For this report, a nuclear weapons test series occurring at the Ne- vada Test Site (NTS) in the continental United States. In this report, Opera- tions UPSHOT-KNOTHOLE and PLUMBBOB. latency period. Delay between exposure to a disease-causing agent and the appearance or manifestation ot the disease (Last' lYY)). leukemia. Any of several types of cancer in which there is usually a disorgan- ized proliferation of white blood cells in the bone marrow (AMA, 19894. Life Span Study fLSS9. Ongoing follow-up of the population exposed to atomic bomb detonations in Hiroshima and Nagasaki, Japan, and progeny; con- ducted by the Radiation Effects Research Foundation. LSS. See Life Span Study. malignancy. See malignant neoplasm malignant neoplasm. A tumor (neoplasm) that spreads from its site of origin to affect other parts of the body. matched. Chosen for comparison based on selected shared characteristics. mathematical model. A representation of a system, process, or relationship in mathematical form in which equations are used to estimate the behavior of the system or the process under study (Last, 1995~. megaton (MtJ. 1 million tons. Here, the explosive energy equivalent to 1,000,000 metric tons of TNT. MFUA. Medical Follow-up Agency, Institute of Medicine. military unit. Organized body of military personnel which may contain only a few, or as many as thousands of members (JAY UOK, l MY. millirem fmremJ. One-thousandth of a rem; equivalent to 0.01 mSv. millisievert (mSv). One-thousandth of a sievert; equivalent to 100 mrem. morbidity. Any departure, subjective or objective, from a state of physiological or psychological well-being (Last, 19951. Illness. morning reports. Documents maintained by the Army and Air Force to record the daily duty status changes, such as arrivals, departures, absences, ill

ABBREVIATIONS, ACRONYMS, AND GLOSSARY X1X nesses, etc. of personnel assigned to company/battery/squadron and head- quarters level units (JAYCOR, 1995~. mortality. Death. mrem. See millirem. MSN. Military service number; identification number used for military service personnel. mSv. See millisievert. Mt. See megaton. muster rolls. Documents that record the assignment of Navy and Coast Guard enlisted personnel aboard ships (JAYCOR, 1995~. NAT V. National Association of Atomic Veterans. NARY. National Archives and Records Administration. HAS. National Academy of Sciences; component of the National Academies. National Center for Health Statistics (NCHS9. Part of the Centers for Disease Control and Prevention; maintains the National Death Index. National Death Index (NDIJ. Maintained by the National Center for Health Statistics, CDC, DHHS; compiles death certificate information since 1979 from all U.S. states, the District of Columbia, and New York City, as well as territories and protectorates; provides name of state in which death oc- curred and death certificate number to researchers (following extensive in- stitutional review board procedures). natural background radiation. Ionizing radiation encountered in everyday life, primarily from terrestrial radioactivity (e.g., radon) and cosmic rays. Ap- proximately 3 mSv per year for persons living in the United States. NCHS. National Center for Health Statistics. NCRP. National Council on Radiation Protection and Measurements. NDI. See National Death Index. NDI-Plus. Recently added NDI service; provides to researchers coded and computerized causes of death (so researcher need not contact each state in- dividually). nested case-control study. A case-control study (study of individuals with an outcome of interest relative to a suitable comparison group) conducted within a subset of an entire cohort. Nevada Test Site JETS). The region in Nevada set aside for the continental atmospheric nuclear weapons testing program. Also referred to as the Ne- vada Proving Ground (NPG) (Gladeck and Johnson, 1996~. nonparticipants. Individuals included in the study specifically identified as not having participated in any nuclear weapons testing or in the bombing or oc- cupation of Hiroshima and Nagasaki, Japan; nor having been a prisoner of war in Japan at the time of the bombing. In this report, nonparticipants are also called referents and members of the referent cohort. nosologist. An individual trained in the classification of diagnoses as recorded in medical records or death certificates according to established categories. not known dead. Not identified as deceased following records investigation.

xx ABBREVIATIONS, ACRONYMS, AND GLOSSARY NPRC. National Personnel Records Center, St. Louis, Missouri. NRC. National Research Council; a component of the National Academies. NRPB. National Radiological Protection Board, U.K. NTPR. See Nuclear Test Personnel Review Program. NTS. See Nevada Test Site. nuclear device. Any device in which the explosion results from the energy released by reaction involving atomic nuclei (Bruce-Henderson, 1982~. Nuclear Regulatory Commission. Independent regulatory agency established by the U.S. Congress to ensure adequate protection of the public health and safety, the common defense and security, and the environment in the use of nuclear materials in the United States. Nuclear Test Personnel Review (NTPRJ Program. Maintained by the Defense Threat Reduction Agency, DoD. nuclear weapon. See nuclear device (Bruce-Henderson, 19824. 01-010. Commissioned officer paygrades. observed to expected. Comparison of number of observed events (e.g., deaths) in one group with expected values based on a standard or specifically cho- sen comparison population. OCMAP; OCMAP-PLUS. Occupational Cohort Mortality Analysis Program. Computer program developed by Gary Marsh and others at the University of Pittsburgh Department of Biostatistics. Office of Technology Assessment (OTAJ. Former nonpartisan research unit within the U.S. Congress that provided congressional committees analyses of emerging, difficult, and often highly technical issues and helped to iden- tify policy options. OTA. See Office of Technology Assessment. outcome measures. Measures of the possible results that may stem from an exposure to a causal factor (Last, 1995~. Oversight committee. A National Research Council volunteer committee of experts that provides guidance, but does not author a report. p. Probability (epidemiology/statistics, e.g., p = .05~. See Appendix C. Pacific Proving Ground ('PPG). Site of most U.S. oceanic nuclear weapons tests. Consisted primarily of the Enewetak and Bikini Atolls in the north- western Marshall Islands of the Pacific Ocean (Gladeck and Johnson, 1996~. participating unit. Military unit designations by which individuals are associ- ated with an atmospheric nuclear test. These are the units that members participated with during the test (JAYCOR, 19954. paygrade. Referred to in military records as a payrate, it is uniform across the branches of service; examples are E3 (third grade enlisted personnel 3) and O 1 (lowest grade officer).

ABBREVIATIONS, ACRONYMS, AND GLOSSARY XXI permanent unit. Military units that participants were permanently assigned to during the operation. It was common for a veteran's permanent unit and participating unit to be the same (JAYCOR, 1995~. personal dosimeters. Devices (usually film badges3 for measuring radiation dose to an individual. personnel roster. Air Force, Army, and Marine Corps documents that list the name, military service number, and grade or rank or rate of each person in a unit on a given date. PHREG. Proportional hazards regression program, SAS. PLUMBBOB. Military code name of atmospheric test of nuclear weapons, 1957, Nevada Test Site. potential radiation exposure. Radiation exposures of uncertain occurrence. PPG. See Pacific Proving Ground. radiation. Energy propagated through space or matter as waves (gamma rays, ultraviolet light) or as particles (alpha or beta rays). External radiation is from a source outside the body, whereas internal radiation is from a source inside the body (e.g., radionuclides deposited in tissues). Radiation Effects Research Foundation (RERFJ. A cooperative Japan-United States research organization. radiogenic. Causally linked to radiation. RADSAFE. Military units or personnel that provide radiation safety monitoring functions. rank. Personnel grades sometimes referred to as ratings; examples include Admiral, General, Private, and Seaman (JAYCOR, 1995~; these are not consistent across branches of service. ratio. The value obtained by dividing one quantity by another (Last, 1995~. REDWING. Military code name of atmospheric test of nuclear weapons, 1956, Bikini and Enewetak Atolls, Marshall Islands. referent. Member of a comparison group or the comparison group itself. referent population. The standard against which a population being studied can be compared. regression. Statistical analysis that seeks to determine the "best" mathematical function to describe a series of data points. relative risk (RR9. The ratio of the incidence of a condition in the exposed population divided by the incidence in the nonexposed population. If there is no difference as a result of exposure, the RR is 1.0. rem. A unit of radiation dose equivalent; replaced by the sievert; 1 rem is equivalent to 0.01 Sv. RERF. See Radiation Effects Research Foundation. risk. The probability that an event will occur. RR. See relative risk. SAS. Originally "Statistical Analysis System," proprietary software package. sea series. Oceanic nuclear weapons test series. In this report, Operations GREENHOUSE, CASTLE, AND REDWING.

. . XX11 ABBREVIATIONS, ACRONYMS, AND GLOSSARY selection series. For this study, the first (or only) of the five studied series in which a member of the participant cohort was present; the selection series for a member of the referent cohort is the series corresponding to the time period and set of unit matching criteria that was used to select the participant cohort. series. An official grouping of nuclear weapons tests. shield (shielding. A body of material used to physically reduce the intensity of radiation. shot. The detonation of a nuclear device; used synonymously with test in dis cussion of the atmospheric nuclear weapons testing program. SI. International System of Units (as instituted in 1960~. sievert (Sib. A unit of effective or equivalent dose. Equivalent dose incorpo rates an adjustment for the fact that different types of radiation (alpha, beta, gamma, neutron) differ in their ability to do biologic damage. Effective dose also incorporates adjustments for the relative sensitivity of different organ systems. The sievert is the SI unit that replaced the rem. 1 Sv is equivalent to 100 rem. SMR. Standardized mortality ratio. See Chapter 9. SSN. Social Security number. statistical adjustment. The use of statistical methods to control for potentially biasing factors in an analysis. statistical significance. See Appendix C. stratification. The process of or result of separating a sample into several sub samples according to specified criteria (e.g., age, sex) (Last, 1995~. survival time. The period of study time that an individual is observed until the occurrence of the outcome of interest or the end of the study. Sv. See sievert. systematic differences. Differences that are not randomly distributed. tests. The detonation of a nuclear weapon (device); also called a shot. thermonuclear device. Fusion-based nuclear weapons. time-dependent. Not constant over time. timescale. Units selected for the measurement of time, for example, calendar time or age. tumor. An abnormal mass of tissue that forms when cells in a specific area reproduce at an increased rate. Also known as a neoplasm. May be benign or malignant (AMA, 1989~. underlying cause of death. The disease or injury that initiated the train of events leading to death or the circumstances of the accident of violence that produced the fatal injury (Last, 1995~. unit diary. The document that recorded the daily duty status changes of per- sonnel assigned to Marine Corps company-level units (JAYCOR, 19954. United Nations Scientific Committee on the Effects of Atomic Radiation (UN- SCEARJ. A committee of the U.N. General Assembly.

ABBREVIATIONS, ACRONYMS, AND GLOSSARY . . . XX111 UNSCEAR. See United Nations Scientific Committee on the Effects of Atomic Radiation. UPSHOT-KNOTHOLE. Military code name of atmospheri weapons, 1953, Nevada Test Site. US. United States. USS. United States Ship, Navy. c VA. Department of Veterans Affairs. validation. Exercise to assess acceptability of data ascertainment. test of nuclear VAMI. See Veterans Administration Master Index. VARO. Veterans Affairs regional office. verification. Efforts to verify that information obtained is accurate. Veterans Administration Master Index (VA MI). Index cards for each VA benefi- ciary; system superseded by BIRLS in 1972. vital status. Determination as to whether an individual is alive or deceased. W1-W4. Warrant officer paygrades. yield. The total effective energy released in a nuclear detonation (Gladeck and Johnson, 1996~.

Contents ABBREVIATIONS, ACRONYMS, AND GLOSSARYxiii SUMMARY1 1 STUDY RATIONALE AND OVERVIEW Rationale, 5 Background, 5 Overview, 7 2 OTHER STUDIES OF RADIATION EXPOSURE OF MILITARY PERSONNEL.......................................................................... Introduction, 8 Military Populations, 9 3 AN OVERVIEW OF THE U.S. NUCLEAR WEAPONS TESTING PROGRAM.............................................................................. GREENHOUSE, 14 UPSHOT-KNOTHOLE, 15 CASTLE, 15 REDWING, 16 PLUMBBOB, 16 Estimates of External Doses, 17 4 DATA SOURCES................................................... Cohort Identification, 20 Nuclear Test Personnel Review Program, 20 National Archives and Military Collections, 21 xxv .8 13 19

XXVI CONTENTS Characteristics of Cohort Members, Including Date of Birth and Vital Status, 21 Beneficiary Identification and Records Locator Subsystem, 21 VA Master Index, 24 Military Personnel Folder, 24 Cause of Death, 24 Veteran's Claim Folder, 24 National Death Index, 25 Population Mortality Rates for Comparison, 25 THE PARTICIPANT COHORT 26 Relationship of Participant Rosters Used in the 1985 Publication and This Report, 29 Participation in Series Other than the Selection Series, 30 ~arms D ~ ¢¢ ~ ~ 1~T'r ~ ^~1] T V l~= NINNY ~ ~l . J~ 7 EXPOSURE DEFINITION AND MEASUREMENT DNA-Provided Dose Estimates, 37 Individual Doses, 37 Alternative Uses of Dose Data, 38 Potential Surrogate Measures of Dose, 39 Decisions for the Analyses in This Report, 40 Future Options for Use of Dosimetry, 41 8 MORTALITY ASCERTAINMENT Fact-of-Death Ascertainment, 42 Fact-of-Death Validation, 43 Date of Death, 46 Cause-of-Death Acquisition, 48 Cause-of-Death Validation, 48 9 ANALYSIS STRUCTURE Overview, 50 Available Data, 50 Analysis, 52 Variables, 52 Type of Analysis, 52 Diagnosis Groups, 54 .36 .42 .50 10 DESCRIPTION OF COHORT CHARACTERISTICS 56 11 FINDINGS 61 Tests of Predetermined Principal Endpoints, 61 Descriptive Analyses of Predetermined Additional Mortality Endpoints, 62

CONTENTS Investigating Leukemia Risk by Land and Sea Series Participation, 69 Investigating Leukemia Risk by Time Since First Participation and Age at First Participation, 70 12 DTSCUSSION........................... Limitations, 73 xxv Fact-of-Death and Cause-of-Death Ascertainment, 73 Statistical Power, 75 Other Possible Confounding Factors, 75 Inadequate Dosimetry, 76 Discussion, 77 Leukemia, 77 Thyroid Cancer, 78 Lung Cancer, 79 Nasal Cancer, 79 Prostate Cancer, 80 Concluding Comments, 80 REFERENCES 83 APPENDIXES A A Review of the Dosimetry Data Available in the Nuclear Test Personnel Review Program, 89 B National Association of Atomic Veterans Medical Survey, 153 C Epidemiology Primer, 159 D Verification of Completeness and Accuracy of the Participant Roster, 168 E Additional Analyses, 183 F Biographical Summaries, 198 TABLES TABLE 2-1. Selected Findings from Studies of Military Participants at - Atomic Tests, 10 TABLE 3-1. Nuclear Test Personnel Review Program-Provided Summary of External Doses (in rem) for Atmospheric Nuclear Test Participants as of 30 September 1993, in Percentage of Series Participants, 18 TABLE 4-1. Sources of Data Items, 22 TABLE 5-1. Official Operational and Postoperational Periods for the Five Series, 28 TABLE 5-2. Estimates and Determined Extent of Participant Misclassification in the 1985 Dataset, 29

. . . XXV111 TABLES-3. Total Number of Series in which Members of Each Selection Series Participated, 31 CONTENTS TABLE 6-1. Closeness of Frequency Matching in the Selection of Referent Cohort Members, 35 TABLE 8-1. Vital Status as of December 31, 1996, 43 TABLE 8-2. Vital Status Data as of December 31, 1996: Process and Availability, 44 TABLE 8-3. Date-of-Death Data: Process and Availability Deaths Only, 47 TABLE 8-4. Cause-of-Death Availability-Deaths Only, 49 TABLE 8-5. Cause-of-Death Source Deaths Only, 49 TABLE9-1. Variables Considered for Analysis and Their Utility, 51 TABLE9-2. Broad Categories of Noncancer Causes of Death as Grouped by ICD-9 Codes, 54 TABLE 9-3. Cause-of-Death Categories Within Broad Category of Malignant Neoplasms, 55 TABLE10-1. Cohort Member Characteristics: Branch of Military Service, 57 TABLE10-2. Cohort Member Characteristics: Selection Series, 57 TABLE 10-3. Cohort Member Characteristics: Age at Start of Follow-Up, 57 TABLE 10-4. Cohort Member Characteristics: Source of Date of Birth, 58 TABLE 10-5. Cohort Member Characteristics: Paygrade, 59 TABLE 10-6. Distribution of Participant and Referent Cohort Members by Branch of Service and Selection Series, 60 TABLEll-l. Number of Observed Deaths and Standardized Mortality Ratio (SMR), by Cohort, and Hazard Ratio for Participants Relative to Referents for Planned Analysis Causes of Death, 63 TABLE11-2. Number of Observed Deaths and Standardized Mortality Ratio (SMR), by Cohort, and Hazard Ratio for Participants Relative to Referents for Broad Cause-of-Death Categories, 64 TABLE11-3. Number of Observed Deaths and Standardized Mortality Ratio (SMR), by Cohort, and Hazard Ratio for Participants Relative to Referents for Causes of Death Within the Broad Category of Malignant Neoplasms, 66 TABLE11-4. Number of Observed Deaths and Standardized Mortality Ratio (STIR), by Cohort, and Hazard Ratio for Participants Relative to Referents for the ICD-9-Defined Subtypes of Leukemia, 68 TABLE11-5. Number of Participants Who Participated in Any Land Series and in Any Sea Series, by Selection Series, 69 TABLE 11-6. Observed Deaths and Hazard Ratio of Participants Relative to Referents, for Land Series and Sea Series Participation, 71

CONTENTS TABLE 11-7. Hazard Ratios for Leukemia, Excluding Chronic Lymphoid Leukemia, by Time After First Exposure, 72 TABLE 11-8. Hazard Ratios for Leukemia, Excluding Chronic Lymphoid Leukemia, by Age at First Participation, 72 XXIX TABLED-1. Instructions to Staff-Common Errors, 170 TABLE D-2. Instructions to Staff Examples, 170 TABLE D-3. Instructions to Staff Availability and Consistency of Identification Data, 171 TABLED-4. Matching of Participant Names on the 1985 and 1999 Study Rosters by Types of Matching Methods Used, 172 TABLED-5. Comparison of Current (1999) Five Series Participant Dataset and 1985 Dataset, 174 TABLED-6. Summary of Completeness of the Nuclear Test Personnel Review Participant List as Indicated by Data Collected by the National Association of Atomic Veterans (NAAV) Health Survey, 177 TABLED-7. Completeness of the Nuclear Test Personnel Review Participant List as Indicated by Veteran Responses to Solicitations in Veterans' Publications, 179 TABLE D-8. Completeness of the Nuclear Test Personnel Review Participant List as Indicated by Veteran Responses to Public Meeting Inquiries, 180 TABLED-9. Estimated Errors of Inclusion and Omission in the 1999 Dataset, 181 TABLE D-10. Nuclear Test Personnel Review (NTPR) Compared to Other Sources, 182 TABLE E-1. Cohort Member Characteristics: Paygrade, 184 TABLE K-2. Cohort Member Characteristics: Type of Military Unit, 186 TABLE K-3. Age at Selection Series, 188 TABLE K-4. Paygrade Groups at Selection Series, 190 TABLE K-5. Standardized Mortality Ratios (SMRs) and Hazard Ratios, by Series and Participant Status, for Selected Causes of Death, 192 TABLE K-6. Standardized Mortality Ratios (SMRs) and Hazard Ratios, by Branch and Participant Status, for Selected Causes of Death, 193 TABLE K-7. Standardized Mortality Ratios (SMRs) and Hazard Ratios, by Paygrade and Participant Status, for Selected Causes of Death, 195 TABLE E-8. Number of Participants and Percentage by Assigned Series and Type of Participation, 196 TABLE K-9. elative Hazards (and 95% confidence interval ICI]) for Leukemia Mortality, by Series: All Participants Versus Single Series Participants, 197

DEDICATION We dedicate this report to J. Christopher Johnson (1 949 ~ 999)

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More than 200,000 U.S. military personnel participated in atmospheric nuclear weapons tests between 1945 and the 1963 Limited Nuclear Test Ban Treaty. Questions persist, such as whether that test participation is associated with the timing and causes of death among those individuals. This is the report of a mortality study of the approximately 70,000 soldiers, sailors, and airmen who participated in at least one of five selected U.S. nuclear weapons test series1 in the 1950s and nearly 65,000 comparable nonparticipants, the referents. The investigation described in this report, based on more than 5 million person-years of mortality follow-up, represents one of the largest cohort studies of military veterans ever conducted.

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