Tobacco Documents Online

SUBJECT: International Cancer Congress, Budapest, Aug. 21-27, 1986 The logistics of the'congress were like M.urphy's Law -- any- thing that could go wrong did. Not even th-e scientific part could help -- that was generally old-hat.. "A-disaster" was the brief (and private) description of the'meeting by a Canadian researcher who represents his country in international cancer matters. He was right on target. Comedy or disaster, or both, the quadrennial meeting of the International Union Against Cancer (UICC,. which is headquartered in Geneva, Switzerland) played to a full house of about 8,000 attendees from 82:-countries and, for the first time, featured a series of international satellite telecasts. A fairly large press contingent, predominantly European and mostly Hungarian, was present to report the event. Several Italian newsmen came because a pharmaceutical company in their homeland had paid their way; the company sponsored a session on an anticancer drug it had de- veloped and also subsidized the congress's daily news letter, a four-page publication that blatantly promoted the company's prod- ucts and also had several antismoking stories during the week. Other writers seemed to have similar benefactors. The subject of smoking and health arose early and often:_even before the official opening ceremony, congress secretary-general SANDOR ECKHARDT of Budapest referred to it during the first of many press conferences. He noted in part that in countries such as Norway and Scotland, where there are strong antismoking cam- paigns, the incidence of lung cancer is beginning to fall. : There were two press offices and one room for press conferen- ces. One, for English-speaking writers, was under the direction of EDWARD MIRAND of Roswell Park Memorial Institute, Buffalo, NY, secretary-general of the 1982 cancer congress and now secretary- treasurer of the Association.of American Cancer Institutes. The ,. .. ... other was directed by 'a Hungarian-'and '='Was,-_-.for-press .- people from Iron'Curtain countries; -the_Hungarian'nominallyYWas in charge of the entire-press'operation;"but virtually all =t~ie-maferial -- and available to'~the -pr _.ess°-came _ ....~fi~o _.__m.~ interviewees -- avail` ' Mirand's -sector. Major. news_ attention":to_".s~inokiing_'and"-;`'cancer ;;developed• early in the meeting because of°-a -press releasethat"_•cited some selected commen,ts from a paper._by -Sir'RICHARD'DOI.L: -on` risks _'of active and passive smoke exposure; stories`, appe.ared,°-in _~many newspapers in a number-of west European nations. As the ~meeting''-,progressed, the eona ahn PUBLIC RELATIONS COUNSEI andamdatmhwa P ; .• ... 0 *13 LINCOLN ROAD •P.O. BOX 223 •GREAT NECK. N.Y. 11022 •(516)452-5715

2. .3 • + y media people were exposed to other well-known antitobacco acti- • vists from around e the world, several of whom were invited to the r~.. press room foi~`-interviews. They included NIGEL GRAY of Melbourne, Australia, and TAKESHI HIRAYAMA from Tokyo, where he formerly was the chief epidemiologist at Japan's National Cancer Center. Doll was videotaped for an international television broadcast. A few writ r attended ll i t rt ~' oki A e s ac ua y . some sess ons on sm er repo ng. for Radio Free Europe, based in London,"-flew-in for two days of coverage; his first, and biggest, story was on smoking and can- cer. The medical, writer for a Houston: paper was there and she also.filed at least two stories.on smoking. The program contained several sessions dealing specifically with various aspects of smoking, including cessation and anti- smoking legislation. Additionally, numerous presentations on the subject were:scheduled for various other sessions. Most of the material was familiar and so were many of the speakers. One pre- , sentation, by a United States scientist,.,was different, if not new; it was ignored or overlooked by the press. (See item No. 2 below.) ~ Many top American Cancer Society (ACS) officers were in Buda- pest and participated in various sessions dealing with smoking. None was a scientist. LANE ADAMS, who recently retired after many years as the society's executive vice president, gave.a plenary lecture. The ACS also had an exhibit with an antismoking theme. The congress site was an old exposition area several miles f rom downtown Budapest. It consisted of a number of utilitarian buildings, many of them seemingly large enough to-contain several football fields each, constructed in helter-skelter fashion on several acres of land. None of the buildings was air conditioned. Meeting rooms in many of the structures had only partial walls -- a speaker in one "room" was heard next door and down the line. In buildings where there were full walls, there were no public ad- dress systems in the rooms, and only a-few rooms had individual' radio receivers. Slide projectors and other equipment were some-;' what less than modern. Many speakers and listeners had a diffi- cult and frustrating time. (This despite the fact that Hungary received more than the normal amount of financial support, espe- cially _ _ cially from the U.S.) ffici l na • a Top UICC o l program s-from the U.S.-didn t see the fi until they arrived in Budapest for the congress. This document i tak , s i . s i th g,` s es -had numerous m om er ,.ag- , ome_amus ssions; etc n o .gravating to affected participants."For."example,:paper No..1098 on the program was followed by No.,5045, then No. 4950; this was a common occurrence.y,Some,numbers were omitted entirely. Discov- ering when: and where'certain papers were being. given became an ering ~ adventure at times. The problem was compounded by-the fact that o the speakers were listed-in a separate document -which also had ~, , numerous errors., _P •_ .'''.. ~> .'l. . ... .3: . u-:. 0 Several prominent cancer -researchers commented privately_..",on. ~ ^' the overall poor scientific quality of the program and vowed that ., 0 4 N ~~ . . .

.:f . 3: the level would be considerably higher at the 1990 congress (in Hamburg, West Germany). However, there were some informative and interesting presentations during the meeting• that included 18 major lectures, 4 special and 12 plenary lectures, 82 symposia, 79 round-table conferences, 5 audiovisual sessions, 190 poster discussions, and more than 4,200 individual poster presentations. Unfortunately, some rather awful material crept in, especially in the-poster sessions. Apparently not all, the sessions had been ref- ereedi, One of the most important scientific reports of the congress came at a session on AIDS (this seemed to attract the biggest turnout of the congress): JEAN-CLAUDE CHERMANN of the Pasteur Institute in Paris disclosed he'd found the AIDS virus present in mosquitoes and certain other blood-sucking insects in Africa. ROBERT GALLO, a leading AIDS researcher at the U.S. National Cancer Institute, questioned the significance of the finding. (Later, and privately, he said he'd been "shafted" by the Frenchman.) For the first time at such congresses, significant attention was paid to the subject of cancer nursing. Indeed, 100 U.S. nur- ses were at the meeting as the result of a grant. There also were the expected sessions on oncogenes (and antioncogenes), immunol- ogy, environmental carcinogens, and cancer therapy (mostly animal work reported by U.S. scientists; human chemotherapy studies of great variety and number reported by Japanese and Italian inves-• tigators). And so on. The highlights: the the Imperial Cancer Research Fund Unit at Radcliffe Infirmary in Oxford, U.K. Doll got considerable new.s attention in several European na- tions because of a press release, headlined "Risk of Lung Cancer From Passive Smoking," citing his claim"that "up to-half the lung cancer deaths among nonsmokers may be-due to passive smoking. The quotation; if not-.a-little 'inaccurate,~7rtas at.least-incom- plete. Doll -had a summary`ofy data' from-'=,-10 ."` studies (in the U.S., Japan, Greece, Hong Kong,_ and the U.K.) on the-'risk,of_.lung can- cer in nonsmokers by-their spouse's smoking habits. Here's what L" 0 ~ he actually wrote: ~ f.- _. . .r . - *'1 `- .. . . , .. . ... ... . ,r _... . . . . .., ., . . , . . . . . ;. _ 0 1. Doll was a busy participant. He was scheduled to give the same paper at twQ.different sessions (morning and afternoon) on the same day. He literally halved the paper, which dealt with the risks of active and passive smoking, and had a different title"'. for each session). The previous day he delivered- a paper by the' (temporarily) absent RICHARD PETO, his protege and colleague at (of.the studies)--are.consistent with an "The great majority increase in risk, when,..the'-spouse smokes,, " ; of 20. to. 50x. I t need not be assumed,-however, that the-risk is the-same in;all,coun- tries, as differences in culture and in housing may well affect .., .. ~ .

_ 4. _ , - L the relative amounts of smoke to which a person is involuntarily exposed by the habits or his or her spouse. Nor can it be assumed that the estimated risks are real, as they depend on the accuracy of smoking histories,and it is possible that self-reported non- smokers -have, in fact, smoked actively to a small extent that is correlated with their spouses' habits unless they have been in- terrogated in much greater detail than they commonly are. If, however, the risks are real, they :can constitute only a-fraction of the total risk as all nonsmokers, whether married to smokers or not, must be exposed involuntarily to:'smoke from other sour- ces. A third test, namely examination of the:trend in incidence in nonsmokers is doomed to -failure as*the rarity of lung cancer in nonsmokers will ensure that measurements of its incidence are too imprecise for changes of a likely size to be detected. "I conclude, therefore, that exposure to tobacco smoke in the ambient atmosphere must be assumed __ to____ cause._. some risk of_ lung cancer, but that the -size of the risk is-uncertain. It may, how- ever, be large enough to account for up to 50% of the risk of lung cancer that i-s-actually observed in nonsmokers." f r In the same paper, but not cited in the press release or, so far as is known, in press stories, Doll discussed a recent review that claimed various animal carcinogens exist in tobacco smoke. He continued: "Unfortunately, it is impossible to estimate the risk that these ambient chemicals may induce, partly because we do not know which of the chemicals in tobacco smoke is respon- - sible for its carcinogenic effect in active smokers and partly because the_ physical state_of__the__various chem.i_cals_-___and_ their _ _ distribution within the respiratory tract is (sic) different when they are inspired actively and passively." - - Doll discussed passive smoke exposure at a morning session that purportedly was to deal with the role of cancer societies in. smoking and health. He was-cochair and lead-off speaker at an af-.. ternoon session on "Analytic Epidemiology!'__ that had a talk on -- passive smoking by DIMITRI TRICHOPOULOS of Athens. He'd leave that topic to Trichopoulos, he said, and would talk about other things, such as the effect of changing cigarette consumption pat- erns and lung cancer mortality trendsn in different countries. (Trichopoulos said nothing new.)> The mean tar delivery in many nations.,is now less than half what it was in the 1950s, he said, but.the-effect on..risk reduc- -- .-_---_---_ ------ tion is is unclear. Lung- cancer mortality rates at-young ages, 35-44 years, have risen in seven countries (Czechoslovakia +17%, France +23%, West Germany +22%, Hungary. +43%,.Italy +7%, Japan +15%, Poland +12%) and fallen-:in five_'-(Australia -15%,. England and Wales -35%, Hong Kong -45%,, The Netherlands -53%, U.S. -32%). In the 65-74-year bracket, there were slight reductions in Hungary and Czechoslovakia, but increases in the other 10 coun- tries, with the highest being in Italy (+44%), Japan (+36%), Hong Kong (+34%), Poland (+32%), and France (+-28%). r., 0 0 w .;

, In England, Doll said, the reduction in lung cancer deaths in younger aged men probably was due to lower tar yields, not to lower cigarette consumption. "Differences in the trends in tar delivery are, I suspect, major contributors to the differences between the two groups of countries," he said. "Certainly, there has been very much less reduction in Czechoslovakia, Hungary and Poland, where the average delivery has remained above 20 milli- grams (mg), and in France, where it remained above 20 mg until recently, than there has been in Australia, England and Wales, and the U.S.A." (The above figures are for men, Doll said, but broadly similar trends exist for women.) (Doll and JULIAN PETO, Institute -of Cancer Research, Sutton, UK, have written an editorial in the October issue of the "Bri- tish Journal of Cancer" in which they say that the evidence sup- porting an association between passive smoking and lung cancer is consistent with an increased risk of 20-30%.) . 2. In an aftei^noon session on the last day of the meeting, HILDEGARD SCHULLER- of the University of Tennessee in Knoxville offered a theory as to how cigarette smoking may induce small cel l 1 ung cancer ( SCLC ): 'The carbon monoxide ( CO ) in -the . smoke -+. creates an oxygen..imbalance in the lung that.leads.to an,.-influx . of endocrine cells, which.rarely are,found:,.in.the,lung. Nitr.osa= ; mines in the-smoke activate the endocrine cells,.;reactive metabo= Glites are::;formed ,, and the- • cells';.eventual.ly,.,ar,e,,.:..tra,n,sf..o.rmed into":,, t$C.[.C-- a Schuller said she developed her theory after experiments in which she used#nitrosodiethylamine -°(DEN),~ a tobacco carcinogen,4 in various human lung cancer cell lines and in hamsters. She was withholding details, she said, because the work is to appear soon in "Cancer-Research." (She's previously reported data saying~'.DEN"#' given to hamsters. induced-,pulmonary adenocarcinomas derived,;fromt;' C1'a"ra-ce11s.;She's been using this model for several years.) , In the hamster part of her work, the animals were given DEN and exposed to CO in an oxygen chamber. All the animals died in about 8 weeks. Their lungs had "lots of tumors" as well as hemor- rhages; the tumors were composed of pulmonary endocrine cells. At the outset, Schuller said that aidous'•,~4~ce11~ . . . _. w . ,.. ..,, -,,-. . _, ... r. . . ~ano'.er~.~:atidN>SCLG,,"t`were=-.ths~'wmost~.~~QAu'ep~~:tYpea~,,o~~'"liup~~:'rCancer,~ in:~ r .•c } t he U':S, ~zY S~nG:e ~ t.hP n,~'~: hp$4.bStg C'pulmooerYX ;~ad~no9 ~F;ctnomas ; ,hav"e become# the most ~T.fr.equent~,.typipkpf.~_0 lyng'3;mal~gnan,cy;~ M okers;y~;she •~ .. . Esai,,dy5 ;~thile ,sq~amous:': Garlcer:o l~as~.;d.eCr.erased~iny incid,ence;~ ~'a,hd~'SCLCeti, Ehas,recn~ined ,.at~+:i^about~t,he,~.sameslevel;..~Later, .an1it~gdthat ' . , .. ~ +s .Y +M M w, . . ~~LC~,was~ ~rare~in, kiuinans"~'arid~~irik~c~omestio4;and~experimental-animal`s. Schuller is planning further experiments in which the levels of CO and oxygen to which the DEN-treated hamsters are exposed can be adjusted so as to control the influx of pulmonary endo- crine cells. She wants to give the animals SCLC and keep them ,

~. -. .. 6. , I alive to see if metastases develop. She worries "a great deal" about the so-called "safe" ciga- rettes, Schuller said, because smokers compensate by smoking more of them. While these cigarettes have lower levels of polycyclic aromatic hydrocarbons, they still contain carcinogenic nitrosa- mines. 3. Lung cancer in females may be more dependent on endogenous factors than is lung cancer in males, according to a hypothesis advanced by scientists at the University of Saskatchewan in-Sas- katoon, Canada. Data from questionnaires answered by 927 lung cancer patients (742 males, 233 females) or their relatives and from the local tumor registry, persuaded D.J. KLAASSEN and colleagues to theorize that females may be more susceptible to the hazards of smoking than men. A poster report noted that females were diagnosed at an earli- er mean age than were men, a finding consistent for each major histologic type ofg lung cancer. Of the females, 42% were diag- nosed before age 60; the figure for males was 25.6%. Female patients were significantly more likely to be nonsmok- ers than were male patients. Among current smokers, the females began smoking at an older age, and smoked fewer years and fewer cigarettes daily than did male patients. The females had more lung adenocarcinomas and fewer squamous cell lung cancers than did the males. Very few female patients were exposed to known or suspected carcinogens or pulmonary ir- ritants at work or elsewhere. 4. ROLAND GRAFSTROM of Stockholm's Karolinska Institute repor- ted that aldehydes in tobacco smoke caused various cytotoxic and genotoxic effects in cultures of human bronchial epithelial cells (HBE) and fibroblasts. Of the aldehydes tested, ~;ae,rolein' was the most cytotoxic in regard to HBE survival and also had potent adverse effects on fibroblasts. Generally speaking, the experiments undertaken by Grafstrom and others (a coauthor was CURTIS HARRIS, National Cancer Insti- tute, Bethesda, MD) showed a variety of adverse reactions induced by the aldehydes tested. These included genotoxic endpoints such as mutations, DNA single strand breaks, DNA protein crosslinks, DNA interstrand breaks, and inhibition of DNA repair. Many of the effects were qualitatively and quantitatively similar in cells derived from human bronchus, buccal mucosa or skin. ` _ The results, Grafstrom said, show (t.~'tb~a~cc~o'~*sinoke:dza'I`dehyde r y' ._h.~ ~e~cer~`~a+.Var~.e,t ofi:eff6ct~sr;,"t`tiat'- relate:r to,;;mGlti.s_tagq,,Cari,cinogen=,j .•

esis in HBE. He noted that aldehydes also occur in vehicular exhaust and in various occupational sources. 5. Richard Peto, in the talk given for him by Doll, cast_part of his comments in the form of advice to Britain's national health authorities -on how to reduce smoking in England. A good part of the paper was a repeat of material from the lengthy re- port he and _Doll wrote several years ago, primarily"on the U.S. situation. _ Smoking is the "overwhelming" factor in human cancer, he said, and causes about one-third of all cancer deaths in the U.K. and the U.S. The figure for the European Economic Community is 25% and "rising fast." Next in importance is alcohol, which is re- sponsible for about 3% of all deaths. Smoking causes additional deaths as a result of heart disease and lung ailments. Priorities should be established for decreasing the hazards in cigarettes and reducing cigarette consumption. The authorities must make adults "confidently" aware of the risk of smoking: about one-fourth of smokers will die six years earlier than they would die if they didn't smoke. There's almost nothing else that is "remotely comparable" in importance to the smoking problem. Peto decried media coverage of "minor" pollutants, saying it detracts from public attention to true cancer-causing agents such as cigarette smoke. New chemicals are being introduced but are being properly controlled. Also, news reports about significant findings from experimental cancer research lead the public to think that smoking is just one of many causes of the disease. As for diet, there's no conclusive evidence regarding nutri- tion and cancer. The protective or preventive effect of vitamins is not supported by valid studies. Many current dietary recommen- dations are based on incomplete data. Nutrition fads should be avoided. (At this session, L. HARDELL of University Hospital in Umea, Sweden, gave a paper in which he discussed various environmental carcinogens, among them dioxin ("Agent Orange"). He accused Doll of "selling out" for having said, apparently recently, that diox- in was not harmful. Doll did not respond.) , 6. "Penetration of a tobacco carcinogen across oral mucosa in the presence of ethanol" was the title of a poster presentation by C.A. SQUIER, University of Iowa, Iowa City. It claimed there was evidence for a synergistic effect between tobacco and alcohol in the_development of oral cancer, but that the reason for the effect was unclear. A po'ssible explanation is that alcohol en- hances the penetration of carcinogens across the oral tissue. v = .V r, h . To study this possibility, measurements were made of the per- meability of porcine oral mucosa to a tobacco-derived carcinogen,

8. nitrosonornicotine (NNN), in the presence of 5% or 50% alcohol. Three regions of oral tissue were used -- gingiva, floor of mouth and buccal cavity; they represented 83 specimens from 16 pigs. Radiolabeled NNN was used in a solution that contained nicotine; the concentrations approximated those found at the mucosal surface of a tobacco user. - - The penetration of NNN across oral mucosa was found not to be significantly changed in the presence of 50% alcohol. However, there was a significant increase in the permeability of gingiva and floor of mouth mucosa, but not buccal mucosa, in the presence of 5% alcohol. This increase occurred after far shorter exposures (1-2 hours) for floor of mouth mucosa than for gingiva• (12-20 hours). The findings suggest that 5% alcohol may act as a vehicle for the transport of tobacco carcinogens across oral mucosa. The findings are in accord with epidemiologic studies showing that the floor of the mou.th is a high risk area for oral cancer.and that there is an increased relative risk of oral cancer for heavy smokers and drinkers. The latter statement applies particularly to those individuals who drink beverages with a low alcohol con- tent, such as beer and wine. 7. A poster from scientists at the American Health Foundation in Valhalla, NY, reported studies in which cancers were induced in rats by the use of smokeless tobacco. The authors were A. RIVENSON, DIETRICH HOFFMANN and STEPHEN HECHT. Ninety-one rats were treated surgically to create a canal in the lower lip. The canal was filled 5 times a week for 28 months with either snuff powder (30 rats), snuff enriched with its own water extract (30 rats) or the extracted residue of snuff (21). The remaining 10 animals served as a control group for monitoring the effects of surgery only. The results: Rats treated with-snuff had 1 squamous cell can- cer:-. of the oral cavity,,, 1 squamous cell papilloma of the hard palate and 1 meningioma. Treatment with enriched snuff caused 1 squamous cell papilloma of the floor of the mouth and 1 nasal olfactory tumor. Treatment with extracted snuff induced 1 squa- mous cell papilloma of the hard palate. The controls had no tu- mors. In a parallel study, rats were treated daily for 30 months by swabbing the oral cavity with either a water extract of snuff (30 rats), snuff enroched with two tobacco-deried nitrosamines (30), water containing the two nitrosamines (30), or water (21). In the group treated with the nitrosamines, 8/30 rats had oral tumors and C/30 had lung cancers. The incidence of tumors in the other groups was not significant compared to controls. A!- ., 8. "Effects tract tumors, of cigarette smoke and vitamin C on respiratory oral leukoplakia and costochondral hyperplasia N N ~ 00

induced by diethylnitrosamine (DEN) in hamsters" -- TAKANORI HARADA, Mitsukaido Laboratories, Tokyo. This poster described an experiment in which male Syrian golden-hamsters receiving 12 weekly subcutaneous injections of DEN-were subjected to cigarette smoke inhalation and maintained on a diet with or without 1% vitamin C_ supplement for 58 weeks. Various types of respiratory tract- tumors, oral leukoplakic lesions and costochondral (relating to -rib- cartilage) hype.rplasia were found in the DEN-treated animals.=The incidence of tumors in the nasal cavity, larynx and trachea= and of oral leukoplakic lesions was significantly higher in the smoke-exposed hamsters than in the control animals. Hamsters that got the vitamin C supplement had significantly lower incidences of nasal cavity tumors and oral leukoplakic lesions and showed much earlier appearance of the tracheal tumors than did the smoke-exposed animals without the vitamin supple- ment. Also, appiearance of the costochondral hyperplasia 'was significantly earlier and the incidence was higher in the vitamin C-supplemented hamsters. The findings indicate that the induction of upper respiratory tract tumors and oral leukoplakic tumors by DEN could be provoked by cigarette smoke and that the provoking effect on the develop-. ment of nasal cavity tumors and oral leukoplakic lesions might be inhibited by vitamin C. However, the occurrence of tracheal tu- mors and costochondral hyperplasia seemed to be accelerated by vitamin C supplement. 9. OSCAR AUERBACH, Veterans Administration Medical Center, East Orange, NJ, was lead author of a poster on histologic type of lung cancer and asbestos exposure. One of the coauthors was LAWRENCE GARFINKEL, chief statistician of the American Cancer Society. Neither man was at the meeting._ The histologic types of lung cancer in 747 men and 107 women from three hospitals and one international study of insulation workers were evaluated. About half the cases were diagnosed from surgical slides and the other half from autopsy slides. Of these, 196 had asbestos exposure. Squamous cell cancer constituted the largest percentage of tumor types and was found with the same frequency in exposed *and nonexposed groups. Small cell carcinoma was found in 25% of as- bestos-exposed patients and in 15% of the nonexposed patients. Upper lobes of the lungs were involved in about two-thirds of the c-ases with asbestos exposure and lower lobes in the other third. Little difference was found in histologic type in cases regardless of whether upper or lower loves were involved. Cigarette smokers who smoked until their cancers were diag- nosed showed no difference in histologic type by amount smoked .1 h ~ 0 Ln ~ 0 N N ~ 1o

10. , and slight but not statistically significant former smokers. differences from 10. Nigel Gray of Australia and MICHAEL KUNZE, professor of community and social medicine at the University of Vienna, co- chaired the session at which Doll spoke about passive smoking. There-were other speakers at the session,.which was on "Smoking or Health: the-Role of Cancer Societies." A. CALUM MUIR, 'of the International Agency for Research on Cancer, Lyon,--France, spoke on cancers other than of the lung that have been associated with tobacco. He discussed smokeless tobacco and the various forms in which it is used around the world. Smokeless tobacco, whether prepared commercially or by "artisans," increases the risk of oral cancer. As many as 400- million persons use smokeless tobacco (mostly in third world nations) and the result is an estimated 100,000 cancers in males and 50,000 in females annually; most of these cancers are in the oral cavity. + The tobacco companies, he said, f aced with lower cigarette sales in developed countries, are now promoting the use of "chew- ing snuff" in the form of "sachets" for oral use. "If the sale of these products, which do not carry any health warning, is allowed to continue, the toll of periodontal disease and oral cancer will be high." B. DON ELLIOT HEALD of Atlanta, chairman of the American Can- cer Society (ACS), said a major U.S. publisher will soon be issu- ing a stop-smoking program that includes a book and both audio and video cassettes. C. The ACS's new executive vice president, G. ROBERT GADBERRY (he recently succeeded Lane Adams), said the U.S. tobacco indus- try was spending $2-billion annually in advertising-promotion. At one point, he said there "may be asmany as 500,000 tobacco deaths each year (in the U.S.)." D. Kunze, who has long been involved in the UICC's smoking control program (headed by Gray), said such programs cannot succeed without the direct involvement of political activists. D. DAVID SIMPSON, head of Britain's Action on Smoking and Health, gave a brief "how-to-do-it" talk about getting and main- taining governmental support at every level in order to combat the "pervasive influence" of the tobacco industry, which is al- ways inviting politicians to sports and cultural events. E. KJELL BJARTVEIT of Oslo, architect of Norway's antismoking program, said smoking was decreasing so strongly in Norwegian youths`aged 16-20 years, he expected this group will be smoke- f ree by the year 2000 or soon thereafter. F. Gray said global antismoking efforts generally are succeed- ing. Smoking is falling at the rate of about 1% yearly in many r•

11. countries. Tar yields now average 11-16 milligrams/cigarette in 22 nations and 17-22 mg in 21 others. The smoking control program that he has long directed for the UICC has been supported since 1976 by an annual US$75,000 grant from Norway's government. (At a subsequent press conference, Gray said tobacco causes a million cancer cases yearly throughout the world, 40% of them in developing countries where tobacco companies are expanding their efforts. His comments were familiar: control of smoking is a pol-~- itical problem; the situation is worsening in third world coun- - tries; the tar content of cigarettes in most developed -nations continues to fall; raising tobacco taxes is the quickest way to reduce smoking.) 11. There's a very high incidence -of head and neck cancer in northern France, according to a poster presentation by L. ADENIS and others at the Centre Oscar Lambret in Lille. The oropharynx cancer incidence appears to be one of the highest found in the literature; laryngeal tumors were second. (There was no mention of tobacco.) _ The data, which are preliminary in nature, came from a Head and Neck Cancer Registry started in 1984 in the Nord and Pas-de- Calais regions that included 2,996 cases by the end of 1985. Males comprised 93% of the patients. There were pathologic diag- noses in 99% of the cases. The ages of 81% of the cases ranged from 40-70 years. The most f requent primary sites were oropharynx (31.5%), hypopharynx and epilarynx (25.5%), oral cavity (22.5%), and larynx (18%). The findings to date show that head and neck cancer is a major public health problem in France and particularly in northern France, according to the authors. 12. While a third of all cancers are preventable and another third curable, if found early enough, minimal resources are-being allocated world-wide for prevention or early detection programs, according to JAN STJERNSWARD, chief of the World Health Organiza- tion's (WHO) cancer unit. (He also was invited to the press room for interviews.) There must be a considerable strengthening of preventive mea- sures, especially in regard to tobacco. Cancer is expected to be a major health problem in nearly all nations by 2000 because of population growth. Lung cancer will soon surpass stomach cancer as the leading cancer globally. From the early 1950s to the mid-1970s, stomach cancer mortality fell by a third in 14 developed countries, but lung cancer mortality rose by the same amount. 13. Another WHO representative, KEN STANLEY, said an estimated 5.9 million new cancer cases are diagnosed yearly throughout the world, with some 3 million of them occurring in developing na- .._ - ,~. r. ~

-~ 12. I tions. Of the 4.3 million cancer deaths yearly, 2.3 million are in third world countries. In Shanghai, China's largest city, cancer jumped from sixth to first pl-ace among leading causes of death from 1960 to 1980. Fur- ther, the overall lung cancer incidence there doubled in the same period; the male death rate of 52.2/100,000 population is now higher than in many developed countries.__ 14. New and interesting data regar.d_ing certain female cancers were reported by two scientists at the University of Bergen, Ber- gen, Norway, in two poster presentations. G. KVALE and I. HEUCH have analyzed some of the data obtained in a 20-year follow-up of more than 61,000 Norwegian women. They found that cancers of the esophagus (25 cases) and of the buccal cavity and pharynx (67 cases) were positively associated with late age at menarche. Findings of this kind had not been previously reported, they said, and may reflect exposure to par- ticular environments'during childhood. Also unreported previously was the finding of a positive asso- ciation between parity (five or more full-term pregnancies) and lung cancer in those women aged 50 years or more at the start of follow-up. The incidence of pancreatic cancer and multiple myelo- ma was significant only in women under 50 years of age at the start of follow-up. (A number of studies have reported that high parity seems to provide a protective effect for cancers of the breast, ovary and corpus uteri.) 15. In an interview printed in the congress's news- letter and at a session on smoking in developed countries, JUDITH MACKAY, a spokesperson on tobacco for the Hong Kong Anti-Cancer. Society, said smoking is no longer a health issue but is now a political issue. Smoking by men in developed nations is decreasing at a much faster rate than is smoking by women, she said, but teen-agers are smoking more than ever. About half the men in third world countries smoke but only 1% of women do; tobacco companies have targeted women for special efforts. "The worsening situation in the developing countries in par- ticular is a result of the ruthless and aggressive.promotional campaign of the tobacco industries," according to Mackay, who also is a consultant on smoking to th.e UICC and the WHO. 16. Describing the "battlefield" in the U.S., ALLAN ERICKSON, American Cancer Society vice president for education, said the TobaccQ Institute wants to spend $100-million to combat antismok- ing regulations in New York State and New York City. Deaths from passive smoking range from 500 to 5,000 yearly, a figure greater than that for AIDS. The tobacco industry denies r• ~ .

13. passive smoke exposure is a threat to health, but a majority of Americans suffer some ill effects from such exposure. The U.S. soon will help the military in Japan and West German in efforts to reduce smoking by-service people. .• 17. Takeshi Hirayama has left Japan's National Cancer Center in Tokyo, where he'd been head of epidemiology for many years, and has organized the Institute of Preventive Oncology in Tokyo. He refused to say who was funding the institute and was- vague about what it would be doing. Hirayama was one of eight persons who received Awards of Merit from the UICC during the Budapest meeting. In a plenary lecture on "Current Aspects of Cancer Epidemiol- ogy," Hirayama made these comments: The most noteworthy finding of recent descriptive epidemiology would be a"tendency-" for a decline in lung cancer incidence and mortality in certain countries -- the UK, US and Scandinavian lands -- in sharp contrast to the steady rise in Japan. Changes in tar content of cigarettes could be responsible for the down- ward trend. However, though tar content has been falling in Japan, lung cancer continues to increase there; this probably reflects a "successive generation effect" resulting from unique trends in the country's smoking history. . "The lung cancer epidemic due to cigarette smoking is really a pandemic covering practically the whole world. Primordial preven- tion must seriously be considered." He briefly cited his findings in regard to passive smoking, green and yellow vegetables and other familiar data. Hirayama had this to say at a press conference (with Nigel' Gray): . _ The average tar content of Japanese cigarettes is 14 mg and is decreasing annually. The situation in Japan is the worst in the world -- the country will soon be No. 1 in lung cancer incidence. Nearly 65% of Japanese men and 14% of Japanese women are ciga- rette smokers. 18. W.A. JEDRYCHOWSKI, who is at the medical school in Cracow, Poland, reported a six-year study of lung cancer incidence based on mortality that indicated a combination of smoking and air pol- lution might cause the disease. Lun,g cancer death rates in Cracow were higher than the average rate in Poland; this could be the result of the greater preva- lence of smoking in the city than in the rest of the country. "Very intriguing" was the finding of -a substantial excess of lung cancer deaths only in male residents of Cracow's central area, which had the highest level. of air pollution. This excess

14. could not be explained solely by'smoking or occupational factors. No such excess was found for females living in the city center. It seems, therefore, that air pollution alone is an insuffi- cient cause of lung cancer, but can exert a carcinogenic effect when combined with other adverse factors such as smoking or occu- pational hazards. - - - 19. "Smoking as a confounder and effect modifier in occupa- tional cancer studies! -- A. AXELSON, University Hospital, Lin- koping, Sweden. Because smoking is a generally recognized factor in lung and- other cancers, the question frequently arises as to what role the custom may have in the observed excess of cancer often seen in various occupational settings. The smoking habits of a particular group of workers don't usually deviate a great deal from other working groups or the general population,-Axelson reported. Therefore, even with can- cers strongly associated with smoking, the effects of confounding in terms of a rate ratio is likely to be about 2 or less (he probably meant risk ratio). The role of smoking as a confounder in occupational cancer studies usually is much weaker than most people believe, even for lung cancer. Smoking may also mask the effects of industrial ex- posure. 20. "Environmental carcinogens can have multiplicative effects in causing cancer when acting together" -- HUGUES RYSER, Boston University Medical Center. Ryser and associates recently found that two carcinogens act- ing together can multiply each other's cancer-causing effect. They observed that cadmium, a heavy metal which by itself is only weakly carcinogenic and weakly mutagenic, enhanced up to 30-fold the mutagenicity of nitrosamines, an important class of environ- mental carcinogens. This effect was first shown in bacterial sys- tems and then in cultured mammalian cells. At the Budapest meeting, Ryser reported that the combination of cadmium and dimethylnitrosamine increased the induction of cancers in rats beyond the level that would be expected if the two carcinogens had only additive effects. I One year after getting a single dose of nitrosamines and 2-4 injections of cadmium, rats developed renal tumors that were significantly more numerous than expected for a simple additive result. There also were increased signs of early cancer in the livers'of the same animals. Further, a significant number of benign and malignant tumors were found at sites that weren't expected targets of either agent at the given dose. . . I . .• r.

These data, according to Ryser, show that weak environmental carcinogens can become strongly carcinogenic when acting together with other agents. This finding may lead to an understanding of the mechanisms by which heavy metals cause cancer. It confirms the validity of simple bacterial tests as predictors of carcino- genicity. Finally, it emphasizes the fact that acceptable levels of cancer-causing substances in the environment must not be de- termined on the basis of single effects, but on the basis of pos- sib_le multiplicative effects of carcinogens that belong to dif- ferent categories and act in concert.- 21. PIERRE BAND, Cancer Control Agency of British Columbia (B.C.), Vancouver, Canada, reported preliminary findings from a study begun in 1983 to identify cancer risk factors in the work area. The subject population consists of all male cancer patients aged 20 years and over identified by the B.C. Cancer Registry. Analysis of questionnaires received to.date disclosed several tumor sites that were significantly associated with cigarette smoking, Band said._ These were oral cavity, esophagus, larynx, lung, bladder, and kidney. At all levels of smoking, the odds ratio for small cell lung cancer was 2-3 times higher than for non-small cell lung cancer, he said. . Only two sites -- lung and kidney -- have so far been analyzed in detail using various internal controls and adjusting for smok- ing. Occupations significantly associated with lung cancer were services, mining and textile manufacturing. Machine working, welding and wood processing were associated with renal cancers. 22. CESARE MALTONI reported the results of long-term carcino- , genicity bioassays of a number of solvents•at the Institute of Oncology in Bolog_na, Italy. It was found that benzene produced a variety of tumors at dif- ferent sites in rats and mice. Toluene and xylenes hastened the onset of tumors in rats, and trichloroethylene (TCE) increased the incidence of hepatocellular carcinomas and lung -tumors in mice. TCE also induced lymphomas, leukemia and Leydig cell tumors of the testes in rats. Methylene chloride increased the incidence of total malignant tumors in rats and lung tumors in mice. 23. Identification of cancer hazards and their attribution to occupation is more difficult than might appear at first sight, according to H. VAINIO of the International Agency 'for Research on Cancer, Lyon, France. About 4% of all cancer cases in industrialized countries have been attributed to occupational exposures, he said. There has been an almost exponential growth in the production of synthetic chemicals since the 1940s while long-term, large- scale animals tests for carcinogenicity did not start until the 1970s. There are many proven experimental animal carcinogens, Vainio said, but there may never be definitive proof of their r, r ~

16. . . • ~ . carcinogenicity in humans. 24. "Potential cellular and molecular targets for chemical carcinogens" -- J.C. BARRETT, National Institute of Environmental Health Sciences, Research Triangl-e Park, NC. In a talk considered significant by his peers, Barrett said most chemical carcinogens induce DNA damage and are mutagenic-at specific genetic loci; however, certain carcinogens, including diethylstilbestrol (DES, a synthetic estrogen), arsenic and benzene usually don't induce detectable gene mutations.'It now appears from further research that nonmutagenic chemicals, such as DES and asbestos, damage the cell at the chromosomal level. He and his associates have found that such chemicals are very effec- tive inducers of morphologic transformation in Syrian hamster embryo cells. Mineral fibers interfere with the normal process of chromosom- al segregation and there's a large increase in anaphase (the third stage of nuclear division of cells) abnormalities. Evidence strongly supports the hypothesis that asbestos causes these chro- mosomal rearrangements, leading to the heritable alteration in cell transformation and growth that ultimately results in tumori- genicity. Barrett said his group has reproduced work by others showing that a single oncogene cannot convert a normal cells into a tu- morigenic one, but that a combination of two oncogenes, e.g., ras and myc, can. Also, the function of tumor suppressor genes must be lost before one gets the expression of tumorigenic cells. He also found that those cells transfected with the ras and myc on- cogenes had a nonrandom loss of chromosome 15, the chromosome whose genes somehow control the expression of tumorigenicity. Barrett feels there are three changes involved in the conver- sion of cells from normal to malignant state. First is the in- duction of immortality which -perhaps involves the activation of oncogenes; second is the loss of tumor suppressor function; and third is an activation of oncogenes. "Cells in our hybrid studies have suggested that tumorigenic- ity is a recessive trait," he concluded. 25. At a press conference, HARALD ZUR HAUSEN of the West German Cancer Research Center in Heidelberg, said the papilloma virus has been linked to certain types of human cancer, notably cervical, skin, respiratory tract, oral mucosa, and possibly the lung. How-ever, only a small number of persons infected with the virus develop cancer and'usually after a latency period of about 20-30 years following the primary infection. The normal prolifer- ating host cell is able to control and suppress the expression of the virus's genomes persisting in the cell. Cancer develops from the modification of those host cell genes that control the viral tn 0 ~ ~ 0 N N N o1 .• r; ~ .•

17. DNA. The papilloma virus interacts synergistically with physical and chemical carcinogens in a number of experimental models. This finding supports the-assumption that cancer of the respiratory tract, lung and oral cavity may result from the interaction be- tween a persistent viral infection and an environmental carcino- gen like smoking, zur-Bausen said. He said that at leas.t_15% of human cancers are linked to vir'- uses. 26. A study of excess lung cancers among tuberculosis (TB) patients was reported in a poster by KUNIO AOKI and colleagues at Nagoya University School of Medicine, Nagoya, Japan. The study material consisted of 4,892 TB cases (2,724 males, 1,277 females) registered in Nagoya in the 1978-82 period; 4,001 cases were followed until the end of 1983, by which time there were 446 deaths. - - Though TB patients died from the disease at rates significant- ly higher than those in the general population, deaths from can- cer of all sites were significantly higher than those in the gen- eral population: twice as high for males and three-to-four times as high for females. Lung cancer rates in the study population were five times higher for males and 10 times higher for females than were rates in the general population. A high colon cancer risk was seen for females, but not f or males. Liver cancer showed no excess risk for either sex, but only females had a higher risk for liver cir- rhosis. - There was an excess incidence of lung cancer among the TB pa- tients. TB precedes lung cancer in most cases.-Location of mos~t cancer lesions was not at the same site of the TB lesions. His- ` tological types of lung cancer were: 32.1% adenocarcinoma; 32.1% epidermoid, 17.9% large cell, 10.7% small cell and other types. 27. At a press conference that covered a wide range of topics, PETER FISCHINGER, deputy director of the National Cancer Insti- tute in Bethesda, MD, said about 28% of the agency's current budget was in the prevention category and that much, of that was aimed at smoking. 28. Indoor exposure to radon constitutes an important source of radiation for people living in temperate regions, said GORAN PERSHAGEN,National Institute of Environmental Medicine, Stock- holm. SLarge-scale measurement programs are needed in many coun- tries to estimate population doses and to identify dwellings with increased radon levels. Indoor. radon levels may be increased by attachment of radon daughters to aerosols, including tobacco smoke particles, he ~ r .

18. said. More studies are needed on the health risk implications of such factors that modify exposure. Some epidemiologic studies indicate that exposure to radon daughters in houses nay increase the risk of lung cancer, but the data are not fully conclusive. - - 29. U. HEINRICH and others (including U. MOHR) at the Fraun- hofer Institute for Toxicology and Aerosol Research, Hannover, West Germany, had a poster describing experiments in which lung tumors developed in rodents exposed to emissions containing poly- cyclic aromatic hydrocarbons (PAHs). Several PAHs, which develop during incomplete combustion or pyrolysis of organic material, have been found to be carcinogenic to animals in noninhalation experiments. Most carcinogenic PAHs are adsorbed onto very fine soot particles when they're emitted. No long-term animal inhalation experiments had been done to study the lung tumor-inducing effect of emissions containing PAHs. The Hannover group exposed rats, mice and Syrian golden ham- sters to three types of emission: diluted gasoline engine exhaust (GE); unfiltered Diesel engine exhaust (DE); and filtered Diesel engine exhaust (FDE). Concentrations of particle-bound PAHs were very low. To get a higher concentration of PAHs, the researchers used coal oven flue gas mixed with the PAH-rich exhaust gas of pyrolized pitch (coal plus pitch exhaust, COE). The animals were exposed 16 hours (coal plus pitch) or 19 hours (Diesel, gasoline) per day, 5 days/week for a maximum of 2.5 years followed by clear air periods of different lengths. The rats and one group of mice were exposed to coal plus pitch ex- haust containing only 0.3 micrograms of BaP per cubic meter in the first 8-9 months; higher PAHs were used afterward. Some ani- mals also were treated with known respiratory tract carcinogens. The results: Accumulations of soot particle were observed onYy in DE animals. Lung tumors were found in DE and COE animals; no tumors were seen in rats and hamsters exposed to GE and FDE and in clean air controls. Adenomas and squamous cell tumors occurred in the lungs of rats with DE and COE exposure. 30. DIANE COOKFAIR and others at the State University of New York at Buffalo had a poster describing a case-control study of bladder cancer risk among truck drivers. Drivers with more than 20 years' work experience who were less than 65 years old at time of diagnosis had 2.5 times the risk of nondrivers in the same age catego'ry. Bladder cancer risk fell with increasing vitamin A con- sumption. Cigarette smoking was positively correlated with risk. However, neither smoking nor vitamin A intake could account for the positive association between truck driving and bladder cancer in younger drivers. r, 01 %A 0 ~ ~ 0

19•. , 31. News about the International Union Against Cancer (UICC): A. The organization's new president is CARL G. SCHMIDT, head of medical oncology at the University of Essen and chairman of the West German-Tumor Center. B. Nigel Gray, chairman of the UICC's Smoking.and Cancer Pro- gram, reported it had generally been quite sucdessful in its ac-- tivities around the world. There will be no let.up and-efforts -- such as smoking control workshops -- will continue-in accord with available funds. A regional group to work with various 'nations has been established in South America and it's- hoped one will be organized in Asia in the "foreseeable future." C. A third Conference on Cancer Prevention in Developing Countries is expected to be held in Seoul, Korea, in September 1987. It will be organized by the UICC's Epidemiology and Preven- tion Program, headed by Takeshi Hirayama. Hirayama and calreagues have written a draft of guidelines for cancer prevention that is now being revised. The final document may be published jointly with the WHO. There'll be a delay in publication of what's called a "Cancer Directory of the World." Work has been done in four countries (France, Japan, Peru, Sri Lanka), but the information obtained was considered to be inadequate and publication has been post- poned. Publication is expected in mid-1987 for an updated, second edition of the UICC's "Cancer Risks by Site," first issued in 1980. Also to be published in 1987 is a new edition of "Cancer Incidence in Five Continents." 32. There were four satellite telecasts f rom Budapest during the congress, each purportedly describing scientific advances being reported in the fight against cancer. Actually, the pro- • grams were taped at the congress and the tapes were then flown to London for broadcast; the Hungarians were either unwilling or un- able to broadcast directly from Budapest. Funding for the tele- casts, a first for the UICC, was arranged primarily by R. LEE CLARK, former head of the University of Texas Cancer Center in Houston, a long-time leader in the U.S. cancer establishment and chairman of the UICC's Committee on International Collaborative Activities. A good portion of the telecasts consistedd of inter- views with prominent scientists attending the congress. • 33. In 1979 the U.S. broke off an agreement for scientific and cultural collaboration with the Soviet Union when Russian troops entere-d Afghanistan. Last year, President Reagan and General Sec- retary Gorbachev agreed-to renew the exchange in regard to cancer research. As a result, leading U.S. and Soviet scientists met in Budapest during the cancer congress to re-establish cooperation in scientific and clinical research into cancer. Y . . r, ~ .

20. At a press conference, JAMES WYNGAARDEN, director of the Na- tional Institutes of Health, hailed the renewal of active collab- oration. He also said that an area of mutual concern between the U.S. and the Soviet Union was the increase in smoking by youths and their increased use of smokeless tobacco products. He said the incidence of mouth cancer was rising in the U.S. and that a similar situation existed in Russia. Somewhat similar comments-about tobacco were made by Russia's chief representative,--=N-IKOLAI BLOKHIN, president. of the USSR Academy of Medical Sciences. I • ., -END- ~