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Diet, Nutrition, and Carlcer Directions for Research Committee on Diet, Nutrition, and Cancer Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1983

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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose nembers are drawn from the Councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consist- ing of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The National Research Council was established 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 of advising the federal government. The Council operates in accordance with general policies determined by the Academy under the authority of its Congressional charter of 1863, which establishes the Academy as a private, nonprofit, self-governing membership corporation. The Council has become the principal operating agency for both the National Academy of Sciences and the National Academy of Engineering in the conduct of their services to the government, the public, and the scientific and engineering communities. It is administered jointly by both Academies and the Institute of Medicine. The National Academy of Engineering and the Institute of Medicine were established in 1964 and 1970, respec- tively, under the charter of the National Academy of Sciences. The work on which this publication is based was performed pursuant to Contract No. NO1-CP-05603 with the National Cancer Institute. Library of Congress Catalog Card Number 83-61699 Inte rn ati on al S tandard B ook Nurnbe r 0 - 30 9 -0 3 3 85 - 3 Available from - NATIONAL ACADEMY P ~:S S 2101 Constitution Ave., NW Washington, DC 20418 Printed in the United States of America

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Comm~ttee on Diet, Nutntion, ar~d Car~cer1 CLIFFORD GROBSTEIN, Chairman JOHN CA IRNS, Vi c e Cha i rma n SELWYN A. BROITMAN T. COLIi~J CAI4PBELL JOAN ]) . GUS S OW LAURENCE N. KOLONEL DAVID KRI TCtIENIS KY WALTER MERTZ AI]THONY B . MI LLER MI CHAE L J . PRIVAL THOLIAS SLAGA LEE WATTENBER& TAKASHI SUGIMURA, Ad vi sor Nat iona 1 Re sea rch Counci 1 S taf f: SUStIMA PALMER, Project Director KULBIR BAKSHI, S taf f Of f icer ROBERT HILTON, Researe.h Associat e FRANCES M. PETER, Editor See Appendix A for further inforination on committee members and staf f . ~.

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Preface In June 1980, the National Cancer Institute (NCI) commissioned the National Research Council (NRC) to conduct a comprehensive study of the scientific literature about diet, nutrition, and cancer. The NCI re- quested that a study committee be constituted to carry out three tasks: (1) "review ... the state of knowledge and information pertinent to diet/nutrition and the incidence of cancer"; (2) "develop a series of recommendations related to dietary components (nutrients and toxic contaminants) and nutritional factors which can be communicated to the public"; and (3) "based on the above state-of-the-art appraisals and the identification of gap areas, develop a series of research recom- mendations related to dietary components and nutritional factors and the incidence of cancer." The NRC Governing Board assigned administrative responsibility for the overall project to the Executive Office of the Assembly of Life Sciences, now the Commission on Life Sciences. Subsequently, a 13- member Committee on Diet, Nutrition, and Cancer and one advisor were appointed to conduct the study. The co~nittee's first two tasks were completed in June 1982 with the publication of a 496-page report en- titled Diet, Nutrition, and Cancer. The specific boundaries of the territory surveyed under the general heading of diet, nutrition, and cancer were defined in this report, which concentrated on the relation- ship between the nutritive and nonnutritive components of diet and the etiology and prevention of cancer. The report also included several interim dietary guidelines for dissemination to the public. The committee responsible for the third task, i.e., the development of recommendations for research, included 12 of the 13 original members and one advisor. The group provided a broad range of expertise in such disciplines as biochemistry, embryology, epidemiology, experimental oncology, microbial genetics, microbiology, molecular biology, molecu- lar genetics, nutrition, nutrition education, pathology, public health, and toxicology. Institutional affiliations and major research interests of these committee members and the NRC staff are presented in Appendix A at the end of this report. The Committee on Diet, Nutrition, and Cancer is indebted to the many scientists who contributed their ideas on directions for re- search and to those who participated in the miniconference on future research. Their names appear in Appendix B. It is also grateful to those who reviewed selected sections of this report at the request of the NRC. The committee particularly takes note of the excellent support received frown the NRC staff headed by Dr. Sushma Palmer and consisting of Dr. Kulbir Bakshi, Mrs. Frances Peter, Mr. v

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vi Preface Robert Hilton, Us. Susan Barron, and Mrs. Denise Belgrave. The support and a ssi stance of Dr s. Diane Fi nk, Andrew Chiarodo, and William DeWys, the past and present NCI pro ject officers for thi s study, are also acknowledged. /~\. Go CLIFFORD GROBSTE IN Chai roan Committee on Diet, Nutrition, and Cancer

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Contents Page CHAPTER 1 - OVERVIEW AND MAJOR RECOMMENDATIOl'JS 1 Strategic Objectives and Priorities for Research... CHAPTER 2 - APPROACH TO THE 3 CHAPTER 3 - DIET AND THE MECHANISMS OF CARCINOGENESIS 9 Research Recommendations 11 CHAPTER 4 - EPIDEMIOLOGICAL METHODSe.~.o. 12 Research Recommendations ~ 15 As se s spent of Di e tary Expo sure s ................. Type s of Epidemiological S tudy.................. Analysi s of CHAPTER 5 - LABORATORY Methods for Identifying Dietary Initiators and 15 16 17 19 Modifiers of Carcinogenesis 20 Methods for Assessing the Effects of Nutrients on Carcinogenesi s. Methods for Identifying Markers Related to Neoplasia i n Hu~nans.............................. 22 Re search Recommendations 23 Initiators and Modifiers of Carcinogenesis...... The Ef fects of Nutrients on Carcinogenesis...... Markers Related to Neoplasia in Hu~nans.......... 23 :23 23 CHAPTER 6 - MACROCONSTITUENTS . . . . . . . . . . . . . . . . . eat 25 Fats. PrOteinee e. J ~ ~ ~ ~ Di etary Fi be ~ 28 ~ V11 28

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viii Contents CHAPTER 6 (Continued) Total Caloric Research Recolumendationse e e e e e e e e e e e e e e ~ e General Recommendations for Epidemiological Research. e e e e e e e e e e e e e e e e e e e e e e e e e ~ e e e e e e e e General Recommendations for Laboratory Researche e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e Specif ic Rec.ommendationse CHAPTER 7 - VIT~IItIS, MINERALS, AND NONNUTRITINIE INHIBITORS OF CARCINOGENESIS e e e e e e e e e e e e e e e e e Vi tamins, Carotenes, and Ret inoid se Vitamin A, Carotenes, and Retinoidseeeeeeeeee Vitamin C (Ascorbic Acid) . e e e ~ e e e e e e e e e e e e e e Selenium ar~d Other Trace Minerals. Molybdenum, Zinc, Iron, Iodine, and Arsenice e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e Nonnutritive Inhibitors of Page 30 30 31 32 32 36 36 36 37 38 38 39 41 Carcinogenesi se e e e e ~ e 41 General Research Recommendations. e e e e e e e ~ e e e e e e e 42 Specific Re search Recommendationse Vitamin A and Carotenese Vitamin C (Ascorbic Acid) e e e e e e e e e e e e e e e e e ~ e e Vitamin Ee e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e 43 44 44 44 Selenium and Other Trace Element se e e e e e ~ ~ ~ e e e 45 Nonnutritive Inhibitors of Carcinogenesiseeee 46 CHAPTER 8 - FOOD ADDITIVES, CONTALIINANTS, CARCINOGENS, AND MUTAGENS e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e Re search ~^^^~ ~- ^~ 47 l~t::~Jllllll~llUct~l~Jll;:,e e e e e e e e e e e e e e e e e e e e e e e e 50

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Contents ix Page CHAPTER 9 - CONS UMER BEHAV IOR Re search Re co~nmend 56 REFERENCES. e e e e e e e e e e e e e e e e e e e e e e ~ e e e e e e e e e e e e e e e e e e e e e e e e e 58 APPENDIX A - COLIMITTEE ON DIET' NUTRITION, ANT) CANCEEL-- AFFILIATIONS AND MAJOR RESEARCH INTERESTS . e 67 APPENDIX B ACKNOWLEDGMENTS e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e 69

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Diet, Nutrition, and Cancer: Directions for Research

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