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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- ~