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Lung Cancer: Causes and Prevention AroCNd/rvs of the lrftmotlorid Lunp Cvrc*r Updals Conhronce, Mrd In /Y.w Oraiorm Loulslom March 3-,S, 1993 Edftd by M.cis Mlz.lf ond P.IaYo Conea N ~ N W C11 F+ N ~ ~

Contents ',hapter 2 Keynote Address: Tbe Control of Lamg Cancer Rschard Peto and Ricliard Dorl Lung Cancer in Sandinavia: T'ime Trends and Smoioag Hibits 1 CAapter 3 Lyly ?'eppo Trends in L=g Cancer Incdence and MoraIitp in the United States 33 Chapw 4 Susae S Dwesq jolbi W.Flannt, and Rager R C.onneay Lung C'ancez and Occupational Expoaures 47 Chapw S w''limm f. Blot Air Pollution and Luag Cancer 63 CAapw 6 Gai 1tii Shj The Causes of Lung Cancer in Lot>;sisna 73 Pelayo CoTrr,o, Isnda WsII'imro Pliclek Elizabedi Fom%arA, Nmuy DalcWr, Youping Lin, WMimn Ha-.cA and Wsaim,e D. joJ!enson , Chcptn 7 Tbe Causes of Lmg Cancer in Texas 83 ('Jiapter 8 Pabicia A Buffles, Linda WiUianv PticJFh T1mm I Irtaxo.4 and chaarro C4ntwr Recent C'sse - Control Studies of Lung Cancer in the United States 01 . Lin da WWimw Pickk, Prlayo C"rea, and EFizabetlc Fontliase ehapter 9' 'lbe Epidemiologic Meaning of k:stolo® in Lung Cancer 117 ,John W. Berg

fJ~cpicr 10 Luag Cancer in Nonsmokers and Low•Risk Populataons 131 Clicpter 11 Joseph L tyo'4 EW" D. Aahx, and JoM W. card„er Ecogenetics of Lung Cancer. Genetic Susceptibility in the Etiaology of Lung C.amccyr 41 Chapter 12 John 1 MWvt&U and aue„ E sate Trends in V'istoiogic Types of Lung Cancer, SEER, 1973-1981 133 Chaptrr 13 Constan« Percy, John W. Harm, and TAomw E Goff"nan Scaeening for Lung Cincer. The Mayo Lung Praject 61 Chapter 14 Robert S. Fonsanc and WillimR F. Taylor Lung Cancer in Japans Effects of Nutrition and Passive Smoking 173 Chapter 15 Takechi H'srcjama Nutritional Status and Cbemoprevention in Relation to Lung Cancer 197 Chaptn 16 Peter Granzuald and William D. DeWys V*itamin A and Lung Cancer in Lo~*; • 211 CJiaptrr 17 Barbma Y. Legardnv, Al,fre+do Lopa-S, and illian D. Johnscn Prevention of Smoking in Adolescents: Current Perspective on a Socal'- Behavioral Intervention 19 Chapter 18 RrcJard 1. Evwcs The Bio1'ogy of Lung Cancer vis-a-vis the Emerging New Biotechnology 229' ter 19 Cha Merls Mi:en Genes of Human Lun Transformin 11J p g g Carcinomas 235 a ~ Gw,Orey M. co'oper w U1

Chapter 20 In Vitro Studies of the Biologq of Lung Canur 247 Chaptrr 21 Drsmond 1 V.Carney, Adi F. G=dar, Frocir Cu=dc , mzd'john D. Mania Radiosctivity and Ggarette Smoke 263 f'J~apter 22 TAonuis H. iP'v~trrs and Joseph R DiFrmao Lung Cancer Incidence and Type of Capretse Smoked 273 f`laapter 23 Petes 1V. Le+e Smolang Cessation Programs and Lung Cancer 285 Chaptcr 24 E11a, R fritz Cancer Pievention and the Smoking, Tobacco, and Cancer Program of the :vationzl Cancer Institute 97 C,Isapttr23 f0seph W. Cullae Lung Cancer and Smolan& Re9ections and Unresotved Lwves 313 Ernst L Wyndes and Marc T. Goodnm Subject Iadex 325

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Pf@ftC@ . The main cause of lung cancer is cigarette smoking; about that the scientific work reported in this book leaves no doubt. Approximately 90% of the deaths from lung nncer and almost one-third of the deaths from cancer of al l kind's nn be traced directly to smoking. In 1982, about 129.000 Americans died from smoking-related cancers, according to estimates from the Office of Smoking of the U.S. Department of Heal th and Human Services. But cancer is not the only disease smokers have to fear: the habit also causes elevated rates of heart disease. According to resezrch reported in this volume. about one in four regular cigarette smokers will be killed before thar time by the habit. And the magnitude of tlse problem is greater than usually is realized. Of every 100 healthy young male smokers in England. statistics predict that one will die a victim of violent crime, two will be killed in tnffic acodenss, and 25 will die from a disease brought about by cigarettes. Similar proportions of deaths will occur in the United States. Women are quickly gaining equality with men in the lung cancer arena: in 1982. lung cancer surpassed breast cancer as the leading cause of ancer dnthsamong women in eight states. The pattern, which is believed to be nationwide, is attributeduo an increase in smoking which began among women 30 years ago. The cost for smokers is high in terms of dollars as well as health. In Louisiana, where 2,100 persons die every year from lung cancer, more than $300 million annually are spent on the purchase of ciga.reues and medical costs and loss of earnings account for approximately $586 million per year. 'Ibe state-espedally its southern area-has one of the highesi cancer ntes in the nation, and many of the studies in this volume look at some of the reasons. Several papers demonstntr that smoking no longer can be considered a personal habit concerning only smokers. Passive smoking-smoke inhaled from nearby smokers-inQeases the lung cancer rate. Research conducted in Japan has demonstrated that nonsmoking wives of heavy smokers suffer a lung cancer risk at least twice as great as nonsmoking wives of nonsmoking husbands. Research has also shown that radioactive materials are a common component of cigarette smoke. Other studies in the book explore the relation- ships of nutrition, smoking, and lung cancer: a precursor of vitamin A that comes from green and yellow vegetables can perhaps lower cancer risks. Smoking can work synergistically with occupational exposure to cancer- inducing agents to increase dnmatially the risk of lung cancer. Studies have shown that some individuals may have genetic factors that make them more susceptible to certain environmental carcinogens. )d

Cigarette smoking is a form of drug dependence because nicotine is an addiction-ousing drug. And cigarette smoking is known to o use cutcer. The addiction to this toxic drug produces many times more deaths than addictions to marijuana, morphine, and cocaine combined. Yet those drugs are illegal. Why then, one may ask, are cigarettes advertised and sold all over the world? When cigarette addiction began about 60 years ag9, its deleterious effects on health were not known because smoking-induced cancers can take as long as 30 years to develop. Now,, cigarettes are a multibillion dollar industry with extrrmely well-organized lobbies and advertising efforts. W'eiI!over $1 billion each year are spent on efforts to promote this addictive and deadly drug; that .sum is mort than the total budget of the National Cancer Inscicute. What can be done? Some of the research in this vodume explores the alternatives. Abolishing smoking, of courss, is unrealistic, but other efforts ht'fld promise. Reducing tar in cigarettes may, over the years, reduce cancer rates, but in absolute numbers, lung cancer deaths are likely to go on increas- ing well into the twenty-first century due to saturation marketing efforts and increases in absolute numbers of smokers. Public education efforts about the deadly effects of srnoking are inadequate at the present time and could be made much more effective. And legislacion-with higher taxes-can make a differ- ence. In Finland ambitious new laws were enacted in 1977: these laws prohibi- ted advertising and sales promotion of cigarettes; forbade smoking in all public places except in designated areas; outlawed the sale of tobacco products to persons under 16 years of age; reserved money from tobacco Lax revenue for developing healih-oriented government tobacco policy; and made the govern- ment responsible for establishing the limits of hasmful' components in tobacco products. Finland now leads the world in reducing lung cancer deaths, especially in younger individuals. The best way to change smoking patterns, which would automatically affect lung cancer oceurrence, is to convince young people never to begin smoking. Parents must be aware of their responsibilities as role models and schoolls should make a health education program emphasizing the haards of smoking a part of instruction from kindergarten through college. The college students from Tulane's Chapter of Alpha Epsilon Delta. recog- nizing the hazards of smoking,, helped with various phases of the conference and continue to sponsor antismoking activities. In fact, plans for this book began when Alion Ochsner became an honorary member of AED (the National Fre-Medical Honor Society). We were seated around'a banquet table in a New Orleans garden district restaurant when the International Lung Cancer Update Conference was fintdiscussed. Dr. Ochsner planned to present a short history of lung cancer at the conference„ for as he told us "..... this disease has grown up with me. It did not exist when I was a medical student." Unfortunately Alton Ochsner died before the conference convened. so this votume lacks his historical perspective. Nevertheless, this book is dedicated;to the memory of Alton C}chsner and we were pleased to have his son. John Ochsner, participate in his stead. We gratefullv acknowledge the continuing

aid of the student membm of AED and their antismoking efforu: as well' as the help of Diana Pi:nckley, Director of Tulane University Relations, and her efficient staff for their aid in cover design and various aspects of production. The orgznizers of the conference are especially indebted to Lorraine Mizell, whose untiring work helped make the meeting a success and whose conunu• ing efforts and administrative expertise helped' produce this monograph. The conclusion is clear: cigarette smoking causes lung cancer. If sdrntists and concerned citi:ens can communicate that simple message to the public, the cigarette advertising salvos and lobbying efforu may all be for naught. There will then be hope of controlling this disease. Merle Mizell, PhD Pelayo Correa, MD

Acknowledgments I sptak on behalf ofTulane Medical Center when I saythat we are pleased and proud that Tulane University has served as one of the cosponsoring universities of this International Lung Cancer Update Conference. It is fi®ng that this monograph be dedicated to the memory ofAlton Ochsner,. MD, an honorary alumnus of Tulane School of Medicine. He served on the Tulane facuit,r for many years as professor and chairman of surgery, prior to esublishing along with four other Tulane department heads what has become the Alton Ochsner Medical Foundation. Dr. dchsner, an internationally known surgeon, dedicated his life to the elimination of lung cancer. We have come far in the baale against lung cancer, but there is stil'l much more we can learn about the etiology: prevention, treatment, and ultimately the elirninataon of lung cancer as a significant cause of h uman suffering. It is through participation in cooperative efforts such as this international conference that we hope to provide an exchange of information which will lead to even more answers about lung cancer. Jolbt, f. iVaa14 MD, CAanatlor Tuktmr C'nis.rrs,ey Medical Cxreter I am gi'ad to acknowledge the success of the joint efforts of our insainations: Louisiana State University, Tulane Universit;.y, Cancer.ks.sociation of Greater New Orleans. and the Board of Regents in organizing and carrying out the Inurnational Lung Cancer Update Conference. The conference addressed' an issue of grrat imporsance to our community and provided up-to-date presentations by some of the best internarional eatperts in the field. The conference has already stimulated important discussions in our scientific community and has estabi'ished' an objestive scientific basis to approach the lung cancer problem in our state. I hope the i.mpetus provided by the conference will continue until a strategy for prevention is developed. Pasal F. Cmsor4 MD! DAe+an Louisicna Stase Universitar School of Medidnr in Neto Orie,ant The Louisiana Board ofRegents and its Advisory Committee on Research and Development are pleased' to have had' the opportunity to sponsor the Internv- dona] Lung Cancer Update Conference. The state of Louisiana. its ciuxens, and its institudons of higher learning are all beneficiaries of this meeting. xv

As a result ofbringing ;he world'i authorities on ;ung cancer research together in New C?riearu to present and exchange research findings about the sute of the an in this field the world has seen that Louisiana is seriously concerned about this drezd disease and intends to promote saentiSc research in order to address this problem. Therefore the srste's image with the scientific communiry has been enhanced worldwide. Lo»k%»na 's otiarsu have benefited from this conferrnce because ahey received the most current and reputable advice from the foremost experu in the field about what they can do to enlunce thcr chances of living lung-aaneez•free lives. They learned that this disease is largely self-inflicted. F'tnally the scholars, scienoxs, and medical practitioners in Louisiana's insti- naoons of higher learning, as well as the scientific comnmuniry outside our coUeges and universities, have benefited from the opportuniry to exchange infotmation -ivith, ask questions of, and interact with the experts who participaeed in this conference. The International Lung Cancer Update Conference was a vemendous success, and we at the Board of Regents are extrcmely pleased to have been a part of it. Wi!?iaw rlrsrnrtsuar, PhD Cowmiai~ ofxiew Eduaidon 1-0u~ 8-,wd 'o/'F.WW Sponsoring a conference is an uncommon event for the Louisiana Board of Regents' Research and,Ikveiopment Program. Generally only research prajects which address issues that are of particular concern to the state tegM hazardous waste, economicdevelopmettt wetlan.ds, the sute's high incidence ofcancerf are supporsed with these sratrappropriated funds, Since one of the goals of this program. however, is to upgrade the quality of research in Louisiana's instins- ticns of higher learning, the Board of Regertts and its Advisory Committee on Researth and Developmeru decided t!'satsponsorship ofthisconference not only was appropriate, but also would be a decided' investment in the future of quality cancer research in the state. In sponsoring hi's conference, the state provided its scientists a rare and perhaps unique opportunity to learn from and exchange ideas with the world's foremost authorities in the lung cancer field in a convenient location and forusn. The knowledge and information the sa,ate's scientists g{eaned as a result ofthu conference should stimulate interest in thie area, as we1P as promote the subm'ts sion of research applications to the R&D Program that are at the forefront ot' knowledge in this field. The response to this conference from the Louisiana scientific and mecl;ca communities was overwhelmingiy positive. The Board of Regents was fortunate that the organizers of the conference were responsible and talented indiwidual: who undertook this task in a serious and dedicated manner. Their hard work anc combined talents, in conjunction with the outstanding speakers arad excellen soentific prexntat;ons, made the conference an unequivocal success. On behal