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? r Research Reports on WMT AT xuw.:.:.4i.~tw~ Tobaa :co and Health Vol. 5 No. 2 IN THIS ISSUE Statistics and disease, p. 1 Moscow Cancer Congress, p. 2 Lung cancer in Canada, p. 4 -tners K awerimlr or, opineon- reqaraung ronaceo -use and nemtu. ,cdarga: apatmt_ robaceo an Widely attention is gireo fo matsriots`whidh ind'uyots that_, differing opinions exiiL This pubiication reports wetm of theaacnwi.do Lung Cancer Ris:~ Reflects Aging, Better Di.tgnosis The rising incidenre of the com- bined diseases of lung -ancer and pul- monary tuberculosis i: a reflection of the longevity of the tuberculous, in- creased diagnostic ac imen, and the occurrence of tuberculosis in older persons, re orts Dr. Milton B. Rosen- blatt, New ~ork chest :1pecialist.* "The increased inci 3ence of bron- chogenic carcinoma may also be a re- flection of aging of the total popula- tion and better diagnoses," he wrote. The assumption that tlie increase was due to tobacco is not consistent with early studies which sho v a progressive rise since World War 1, he noted. Dr. Rosenblatt said that at one time it was widely believed :hat cancer did not occur in lungs infec#ed with tuber- culosis. Now, he said, ,r_ athologic stud- ies have shown a "high degree of cor- relation between signi ficant calcified tuberculosis foci and the site of origin of bronchogenic carcinoma." These foci, he suggested, may act as cancer- causing irritants. He said that in pre-iious years tu- berculous patients did not live long (Continued on -vage 5) * "Co-existence of lung :ancer and pul- monary tuberculosis." Cin.ical Medicine, June 1962. September-October 1962 New study says . Marital Data Show cFallacy' of Using Correlations to Find Disease Causes Special Report This issue contains a special re- port on the recent International Cancer Congress held in Moscow and attended by about 5,000 cancer researchers from over 70 countries. The report was written by a staff correspondent who at- tended the meeting. 'Emotional Stress Seen Heart Disease Factor After surveying 10,000 physicians, dentists and lawyers, a cardiovascular specialist reports that emotional stress may be an important accelerating fac- tor in coronary heart disease when the diet is relatively high in animal fat.* "All were North American males, (Continued on page 4) *"Emotional stress and coronary heart dis- ease in American physicians, dentists and lawyers." American Journal of the Medical Sciences, June 1962. Geographic Di Terences in Lung Cancer Rates Show Need to Study Various Suspect Factors "The definite discrepancies in the lung cancer rates for aifferent coun- tries, states, provinces, and cities" in- dicate the need for continuing study of various possible causative factors, a team of six scientists reports.* "It appears that ev: ry community has an atmospheric caroinogenic spec- trum which depends up nn local condi- tions which include not only industrial activities and traffic cDnditions, but also climate, solarizatio a and geologic conditions," they said. * "Carcinogenic bioassays on air pollutants." Archives of Pathology, Au;;ust 1962. Further investigation of the relative role and importance of various fac- tors "should include an investigation not only of the aromatic and aliphatic hydrocarbons present in the particu- late phase of air pollutants but also of metallic, mineralic, and radioactive constituents as well as the relative chemical stability and the physical status of some of these elements in the atmosphere," the six researchers recommended. In a discussion of the smoking-lung cancer question, the authors said :"The (Continued on page 6) The statistical correlation between marital status and death rates from most diseases, including lung cancer and heart disease, shows the "fal- lacy" of relying on such correlations to determine the significance of envi- ronmental factors in the causation of disease, writes Dr. Joseph Berkson, chief medical statistician of the Mayo Clinic.* Dr. Berkson noted that annual death rates from all causes are highest among divorced persons and lowest among married persons, regardless of sex. The same holds true for lung can- cer and heart disease, he said. Death rates for these diseases increase in this order: married, single and divorced. "Examination shows that all, or al- most all, diseases are similarly corre- lated, many of which it is virtually incredible to relate to environmental factors," he said. "If we take the hint from these find- ings that the observed differences of death rates may be determined consti- tutionally, rather than environmen- tally, the possible implication for the (Continued on page 4) * "Mortality and marital status." American Journal of Public Health, August 1962. Three Principles Suggested In Studying Cancer Causes A Mayo Clinic pathologist offers three basic principles to remember in studying the causes of cancer: "1. Cancer is multicentric. 2. A time lag (probably 5 to 15 percent of a life- time) must elapse between exposure to a carcinogen and development of a cancer. 3. Different individuals re- spond differently to carcinogens." In an article on causative factors in (Continued on page 5) *"Etiologic factors in cancer." Journal o/ the Arkansas Medical Society, July 1962. TI KU 000006580 TIMN 0130756

Special Report I Eighth International Cancer ( Virus-Cancer Theory Highlights Meetit.g Moscow - Discus-ions of an ac- knowledged though =;ti11 undefined role for viruses in the ~-,rigin of cancer in animals and possibly man domi- nated the six-day Eighth International Cancer Congress held :his summer at the University of M :)scow and at- tended by about 5,000 scientists from over 70 countries. In a report on the Congress, The Lancet of August 25 s?id that "By far the most striking d;-velopment re- vealed by the Congr~:;s was the tre- mendous change in stai us of the hypo- thesis of the viral etio ogy of cancer. Altogether more than 50 papers on this topic were preserited." (At the 1958 Congress in London the program included only four papers specifically on viruses and cancer.~ Scientists in Moscow were talking about viruses in main lectures, panel discussions, and in section meetings on immunology, etiology, carcino- genesis, and biology of the cancer cell. But, as Prof. L. A. Zifber of Moscow said in a major lectur:>, the status of knowledge about viru=es and human cancer is largely that "we know the questions we have to .nswer." Discussants of the ~,iral theory of cancer were cautious in their claims, and opinions varied widely as to the relative importance of viruses and their exact place in human cancer. Zilber said that aninial and labora- torv work with viruses indicated: (a) Cancer viruses may be latent and activated by a nu, iber of factors including aging, the eff:-ct of radiation or environmental influ- nces. (b) Viruses may play primarily an initiating role in can ;er, and their presence may not be necessary for the growth and spread of the malig- nancy. This would exp ain why it has been difficult to deteci viruses from human cancer that has progressed to clinical manifestation. He suggested looking for a viral :.gent in early stages of tumor development. (c) The fact that vii uses can some- times be found in ani_m__al cells without tumor formation suggn~sts antibodies are at work. This hokl:5 out hope for possible creation of immunity for at least certain types of cancer. (d) Other compounds and agents that are considered cancer-causing may not be the basic cause of cancer but they may somehow permit the tumor virus to go ahead and do its work, either by upsetting the internal regulation of the cell or by acting as a repressor of the antibodies. Dr. Frank Horsfall of SIoan- K:ettering Institute in New York said in a panel discussion that more than 30 viruses have now been shown to be cancer-causing for animals and that one virus has induced more than 20 different types of cancer in mice. Dr. Horsfall advanced a "unifying concept" of cancer which recognizes that while there may be a number of factors that may produce a change of a cell from normal to cancerous, the essential alteration in the genetic ap- paratus of the cell is similar in each cancer. In a lecture on advances in knowl- edge of the carcinogenic process since 1958, Prof. Alexander Haddow of Great Britain, new President of the International Union Against Cancer, listed viruses among new cancer sus- pects in the past four years. His list also included metals, plastics, aro- matic amines, endocrine causes, anti- biotics, and radiation. Dr. John J. Trentin of Houston; Tex., reported that a human-type adenovirus had induced lung cancers in experimental animals. (Reported fully in Science, Sept. 14, 1962.) This was confirmed by Dr. Robert J. Heub- ner of the U. S. National Institutes of Health, who said there have been "momentous developments" in cancer- virus research but that perhaps the most serious difficulty is "primarily a philosophic one - an intellectual im- pediment which often blocks full ap- preciation of the simplicity of the virus hypothesis even in relation to well-known cancer viruses." Environmental Influences Continuing studies of environ- mental and occupational influences on cancer incidence were reported at various sessions of the Congress. There also was recognition that "host factors" of predisposition play an important role. One panel discussion was devoted to reports on occupational cancer research. Prof. L. M. Shabad, secretary gen- eral of the Congress and Russia's lead- ing environmental cancer research sci- entist, reported Russian scientists regularly induce lung cancer in ani- mals by experimental implantation of cancer-causing chemicals. In answer to a direct question dur- ing discussion, Shabad said that many agents may contribute to the origin of lung cancer, such as pollution of air, combustion gases and radioactive substances, but it was not possible to say that these or the smoking of to- bacco were the primary cause. "I am not satisfied with this an- swer," Shabad told a news conference, "and that is why I have devoted my life to research on this question." Lung cancer appears only under specific conditions, he said, and any of the suspect environmental factors must fall on fertile soil to result in lung cancer. He described the ap- parent susceptibility of experimental animals to cancer-causing challenges and said human beings could have some predisposition that would ac- count for lung cancer not occurring in all exposed to the same challenges. Prof. J. H. Maisin of Belgium, past president of the International Union Against Cancer, followed Shabad by saying "we do not know the exact cause of any cancer," and that this ap- plies to lung cancer as well. Dr. W. C. Hueper of the U. S. Pub- lic Health Service said occupational environmental hazards pose increas- ing problems. He called for an inter- national clearing house of informa- tion relating to occupational hazards. Dr. Geoffrey Dean of Port Eliza- beth, South Africa, said British immi- grants to South Africa, New Zealand and Australia have a higher lung can- cer incidence than do immigrants from other European countries or native- born South Africans, New Zealanders and Australians of similar origin. "In the pure atmosphere of rural South Africa, moderate cigarette smoking causes no significant increase in the lung cancer risk," he said, "although in the cities the lung cancer incidence is higher among cigarette smokers than nonsmokers." Dr. V. I. Fershtudt of Moscow re- ported a five-year study of lung cancer incidence in a large industrial city and found "there were a number of dwelling houses or localities with a 2 TIMN 0130757 TI KU 000006581

1 V ongress • Viruses, Environmental Influences, Lung Cancer, Geographic Patterns 3 TI1VIN 0130758 high incidence of lun;; cancer, in con- trast to other houses with a much lower incidence or complet:: absence of the disease. The houses ^-hich were seats of infection as a rule were situated in the immediate proxi~aity of some in- dustry enterprise . . ." Investigations rela:ing to tobacco smoke were among eports in other sessions of the Congress. Dr. Francis Roe of Great Britain reported testing the carcinogenic activity of benzpy- rene at 125 times the -•eported concen- tration of this substance in cigarette smoke condensates and getting results that suggest this chemical plays "only a minor role" in the tumor yields on animal skins with such condensates. He said smoke con,ensates showed promoter activity in mouse skin tests if applied following s strong carcin- ogen. Also referring to work with benzpyrene, Dr. Kath:~rine Herrold of the U. S. National C ancer Institute said "whether or not this carcinogen plays a role in the development of lung cancer in man is still uncertain." Various methods o' inducing lung cancer in animals wit',. chemicals were reported at the meeting, including the induction of pulmonA y adenomatosis in mice which were given orally an oilve oil emulsion of dibenz(a,h)an- thracene by Drs. Kat, ierine Snell and Harold Stewart of the National Cancer Institute. Leslie Elson and Dr. R. D. Passey of Great Britain reported studying the effects of nicotine on the metabolism of animals, and the influence of in- creased dietary protc-n on these ani- mals. They said studi: s with a human volunteer indicated :somewhat com- parable results. Passey said he had unsuccessfully tried for 71/2 years to induce lung cancers in animals by exposing them to tobacco smoke inh;dation. Robert W. Buechley of California reviewed epidemiolo!;ical studies of lung cancer and said 1 ang cancer mor- tality is proportional to the amount of arsenic in the enviro.iment. Species differences in response to cancer-causing subsr:-nces continued to be a subject of ma, y reports. Prof. L. A. Gritsiute of Rus_;ia reported dif- fering reactions in the lungs of differ- ent species to "real an 3 supposed can- cerogenic substances.'- The reaction of the lungs "depends greatly upon the species of animals," he concluded. The role of the liver in metabolizing chemical carcinogens also varied with species, according to Drs. John and Elizabeth Weisburger of Bethesda, U. S. A. This emphasizes the impor- tance of "endogenous factors which promote, hinder or in other ways mod- ify the action of chemical carcino- gens," they said. Dr. Paul Kotin of California described production of epidermoid lung cancers in C57 black mice exposed to aerosols of carcino- genic hydrocarbons after previous infection with influenza viruses. He also reported that mild injury to the liver of the animals results in an alter- ation in the metabolism of the car- cinogen that increases the tumor yield as compared with controls exposed to the carcinogen alone. Various methods of improved bioas- say were advanced. Dr. P. R. Peacock of England told of results in 16 weeks from carcinogens on embryonic tis- sue grafts that compared with longer- term results from skin-painting with similar chemicals. Cancer of the Lung The two Congress sessions on "Car- cinoma of the Lung" were devoted almost entirely to discussion of better methods for early detection and diag- nosis and for improving treatment following surgery. Dr. Abraham Lilienfeld of Balti- more, and Prof. A. M. Charny of Rus- sia both reported sputum cytology as effective in diagnosis. R. C. Burr of Canada, A. Novikov of Moscow and A. Ficari of Italy, were among those reporting that radiation therapy sig- nificantly helped the survival rate of lung cancer patients following surgery. E. V. Ermolayeva of Moscow re- ported retroactive study of x-rays of lung cancer patients revealed "most of the primary lung cancers originate in the sublobar bronchi and in the minor ones." The researcher suggested anal- ysis of x-rays as a method of early diagnosis of lung cancer. Opening the lung cancer sessions, Dr. Joseph Balo of Hungary reported his study of 300 cases of lung cancer and said that to. explain the etiology of the disease, other factors besides smoking must be counted upon. A ma- jority of central lung cancers were found in the right bronchus. This, he said, "cannot be ascribed only to the effect of smoking. The development of peripheral scar cancer cannot be explained by the effect of smoking either. The scar cancers originate mostly from tubercular foci or scars of infarcts." Summarizing the lung cancer ses- sions, Section Chairman Novikov of Moscow said that the primary cause of lung cancer is unknown. Not only smokers but nonsmokers have lung cancer, he said, and lung cancer ap- pears in villages as well as in cities; environmental factors are not the pri- mary causes of lung cancer. Geographic Patterns International exchange of informa- tion about cancer of various sites was seen as leading to better understanding of the origin and control of cancer. Coordinated reports of cancer in the 15 republics of the U.S.S.R. were said to be helping to assess factors respon- sible for cancer. One U.S.S.R. team of experts said: "Skin cancer is commoner in the southern regions, as compared to the northern, and is undoubtedly related to the climatic and geographical con- ditions of those areas and to the meth- ods of protection from sunburn in the local population. Mouth cancer is more frequent and lung cancer is more rare in regions of Middle Asia where tea drinking is more frequent than smoking. In those regions where drinking hot tea is common, and espe- cially with eating fish with fine bones, cancer of the esophagus is more com- mon. Where cancer of the uterine cer- vix is more rare, cancer of the breast is more common and vice versa." In the Tatar Republic, stomach cancer is highest in incidence, and throughout Russia the stomach is one of the more common sites of cancer. On the other hand, Dr. John R. Hel- ler of Memorial Sloan-Kettering Can- cer Center in New York said stomach cancer is in such a rapid decline in the United States that "it's hard to find clinical deaths to study." This decline is in sharp contrast, he said, to the increase in lung cancer, which may be due to a number of causes. The lung cancer increase could be related to the decline in stomach cancer, he added, but there is as yet no evidence to support this. TI KU 000006582

b X Statistics and Causes of Disease (Continued f rom ,)age 1) fallaciousness of enviroiimentally ori- ented theories is of revelutionary im- port, while the suggesti~ n that consti- tution can have such exq iisitely differ- entiating effects is itself challenging," said Dr. Berkson. "Then if we wonder whether the whole mav not be due to systematic errors in the statistics, we can find support for this too." "It is easy to fall into the practice of selecting particular diseases asso- ciated with particular factors that ap- pear plausible, while ignoring similar associations of the same diseases with other factors, and of th=~ same factors with other diseases," th:: Mayo statis- tician added. Dr. Berkson called this an example of the "fallacy of misplaced concrete- ness." He said "The ten, ency has been flagrantly exhibited in the recently much-p iblicized correlation between smoking and death rate from lung canc. r." He said it has "been o verlooked that the correlations found a-e general and concern all classes of di:;ease, not only lung cancer." It has been argued, h.; said, that the lung cancer death rate is greater among males than among females be- cause men smoke more. "Then again it is argued that the death rate from lung cancer is greater ir} urban than in rural communities because of the greater smoking rates characteristic of urban communities or because of air pollution. "But the death rates from virtually all homologous cancers are greater among males than among females, and so are the rates froi'n virtually all non- cancerous diseases. So also the death rate is greater in urban communities for other cancers - cancers that can- not be attributed to either smoking or air pollution - and for non-cancerous diseases as well." He noted that the sex differential and the urban-rural differential of death rates from diseases have been known for 300 years "and have not been adequately explained for the same length of time." Dr. Berkson said "Unless we under- stand the physical basis of the relation of a factor to disease in general, it is hazardous to speculate about its causal relation to a particular disease." Emotional : Aress and Heart Disease (Continued f rom page 1) aged 40 to 69, who prol>ably show no marked differences in d.et or heredity in the aggregate, but w-io are subject to specifiably varying degrees of oc- cupational stress," wrcte Dr. Henry I. Russek, consultant at the U. S. Pub- lic Health Service Hosp .tal, Staten Is- land, N. Y. ' Dr. Russek's findinw-: Physicians. General practitioners and anesthesiologists were judged to be in a "high stress" a.ea of medical practice, and pathologi=ts and derma- tolo;ists in a "low stress" area. General practitioners; iind anesthesi- ologists had distinctly hj';her coronary heart disease prevalence rates than the other two groups. The prevalence of coronary heart diseas= was highest among general practiticners and low- est among dermatologi!:ts, the survey showed. Dentists. General dental practition- ers and oral surgeons showed dis- tinctly higher rates than periodontists, whereas orthodontists h:-id an interme- diate position. The prevalence of cor- onary heart disease was lowest among periodontists and highest among gen- eral practitioners. Lawyers. Four classes were chosen and ranked in descending order of "stressfulness": general practitioners, trial lawyers, specialists (excluding patent and trial lawyers), and patent attorneys (nontrial). As with physi- cians and dentists, a "striking ten- dency" was seen for coronary heart disease prevalence rates to increase with advance in stress rank in this occupation group. Dr. Russek also referred to a pre- vious study of his which indicated that "emotional stress of occupational ori- gin may be far more significant in the etiologic picture of coronary disease than heredity, dietary fat, tobacco, obesity or physical activity." In summing up his findings relating to the professional groups, he con- cluded: "The findings of these sur- veys lend support to clinical and ex- perimental studies which suggest that emotional stress is an important ac- celerating factor in atherogenesis when the diet is relatively high in animal fat." 4 Canadian Data Indicate Lung Cancer Mortality Near Peak Canadian statistics are consistent with "the hypothesis that the male lung cancer mortality rates are near a peak," says Dr. E. W. R. Best, chief of the epidemiology division of Can- ada's Department of National Health and Welfare.* "However, only time will tell if this is so," he said. His report noted that in each five-year age group, aged 45- 49 and over, there has been a distinct increase in male lung cancer death rates in Canada since the three-year period 1931-1933. The greatest in- creases were seen in the age groups of 65-69, 70-74 and 75-79, he said. But in the separate years of the most recent three-year period, 1958-1960, the progressive increase in mortality rates noticed in the three-year groups is not seen, Dr. Best said. "Rather the rates show some ten- dency to stabilize," he said. "This is consistent with the hypothesis that the male lung cancer mortality rates are near a peak." There was little change observed in the female lung cancer mortality rates during the periods studied, his report said, and the changes observed did not form any regular pattern, even for those groups age 65-69 and older. * "Lung cancer mortality trends in Canada." Presented at annual meeting, Canadian Thoracic Society, June 13, 1962. Development of Emphysema Reported Still an 'Enigma' The development of pulmonary em- physema "remains an enigma," report three Chicago researchers following a study of lungs obtained at autopsy from 34 women and 18 men with no history of chronic pulmonary disease.* It seems likely, they said, that "mul- tiple factors - some preslisposing, some precipitating - act 'in concert to produce the disorder, and that these factors are not the same in all cases. "Chronic bronchitis and, especially, emphysema are seen predominantly in men," wrote Drs. Gordon L. Snider, Jerome S. Brody and LeRoy Doctor of Michael Reese Hospital and Chi- cago Medical School. "Although the reasons for this are not known, the sex incidence does not appear to be determined by occupation or smoking habits." * "Subclinical pulmonary emphysema." American Review of Respiratory Diseases, May 1962. TI KU 000006583 7'14N 013-9759

I . I Factors in Lung Cancer Rise (Continued f ront gage 1) enough to reach the calcer age. But with the advent of chemotherapy, more patients are living longer, he said. Also, the previous pretl ilection of tu- berculosis for young a, ults has been replaced by an increasi ng rate of in- fection in older persons. Many Questions U ianswered The rise in lung cancer incidence "still requires clarification," Dr. Ro- senblatt said. "The attem pts to simplify the problem by attrib iting the in- crease to the alleged ca rcinogenic ef- fects of cigarette smoki.ig leave many questions unanswered. "The rate of increas:~ of broncho- genic carcinoma has ~ hanged little since the days of World War I, when cigarette smoking becarne greatly pop- ularized and the allegrd carcinogen could scarcely have had time to exert an effect." "Although the numb:~r of cases is increasing, the rate o,' increase is declining, despite the i lcreased con- sumption of cigarettes," he said. "Fur- thermore, there has been no substan- tial biologic confirmation of the sta- tistical studies on smoking and cancer; bronchogenic carcinom:- has not been produced experimentally by tobacco or its products. "The disease continu; s to be essen- tially one of men despitc the increased smoking habits of women. Factors such as increased diag-.ostic acumen and longevity appear tc offer a more rational explanation than statistical studies with questionable conclu- sions." The sex and age distribution of patients with the combined diseases, Dr. Rosenblatt notes, parallels that of carcinoma itself. After 300 Years Dx. William T. Mil;on wrote in a letter to the editor o:' Guy's Hos- pital Gazette, London, April 21, 1962, that he and a colleague "do not think it reasonabl:: to imagine that tobacco, after i,aving been smoked for more thai 300 years, with little harm to t ie smokers, should suddenly cease to be some- thing of a comfort, and become in- stead a deadly killer, for that is what the Royal Colle;;e of Physi- cians suggest." Serum Lipid Level May Stem From Heredity, Study Shows Clinically normal young males with a parental history of coronary heart disease had higher levels of certain serum lipids than a similar group with a negative family history for this dis- ease, according to a study by Dr. David R. Bassett of the University of Pennsylvania Medical School.* He reported that no significant dif- ferences were found between the sub- ject and control groups in stress, smok- ing, alcohol ingestion, circulatory la- bility, average daily intake of calories, or proportion of calories derived from fat. He compared 20 white male medi- cal students having positive parental history of coronary heart disease with a group of eight students having a negative history. The study "revealed significant dif- ferences in serum cholesterol. phos- pholipid, total esterified fatty acids, and total lipids; and in relative weight, height, and bi-iliac diameter," said Dr. Bassett. * "Serum lipids in young males with par- ental atherosclerosis:' American Journal o/ the Medical Sciences. June 1962. Primary Lung Cancers Often Found in Wild House Mice Two National Cancer Institute sci- entists report that primary lung can- cers may be the most frequent neo- plasms in wild house mice and the reason is believed to be hereditary fac- tors.* Drs. Howard B. Andervont and Thelma B. Dunn found tumors in 98 mice of 225 necropsied. They said 21% of the tumors were pulmonary, 10% reticulum-cell, 5% each granu- losa-cell of the ovary and hepatomas. and 4% hemangio-endotheliomas. The pulmonary tumors were simi- lar both microscopically and grossly to those occurring in laboratory mice, they said. However, almost all the wild mice developed single tumors as contrasted to multiple tumors often found in highly inbred mice such as strain A. "The consensus is that hereditary factors are important, if not predom- inant, in their occurrence," the scien- tists said. "The most common tumor encountered in genetically heterozy- gous wild mice may also be controlled largely by hereditary influences." * "Occurrence of tumors in wild house mice." Journal o/ the National Cancer In- stitute, May 1962. 5 TIlVIri 0130760 Tobacco and Health Published by THE TOBACCO INSTITUTE, IIYC. Address correspondence to: Editorial Office Tobacco and Health 150 East 42nd Street New York 17, N. Y. Cancer Research Principles (Continued f rorn page 1) cancer, Dr. Arnold L. Brown said the etiology of cancer includes "poorly understood, complex, presently uncon- trollable primary causes, such as cellu- lar and molecular mechanisms. It also includes immediate causes of more current interest, such as viruses and trauma." He urged caution in accepting "with- out question" the statistical associa- tion between smoking and lung cancer. Dr. Brown said "The evidence for this association is statistical and is the re- sult of the coupling of a diagnosis of carcinoma of the lung with historical information supplied by the patient or his relatives on the patient's smoking habits. "Despite the increasing evidence which is purported to link smoking and lung cancer, I believe that some caution should be exercised in accept- ing this association without question," he said. "Considerable evidence is at hand which reveals in detail the asso- ciation of lung cancer with various air pollutants," he wrote. "That carcinoma of the lung is much more prevalent in urban than in rural areas has been cited as evi- dence that air pollution is an impor- tant factor in the causation of lung cancer," Dr. Brown said. "Furthermore, it should be kept in mind that only a relatively small por- tion of people who are heavy smokers eventually develop carcinoma of the lung. "For this reason alone," he said, "it is obvious that there is a large in- dividual variation in the response to the carcinogenic activity of tobacco smoke, if such actually exists. "It would seem prudent with our present knowledge to accept tobacco smoking as one possible cause of lung cancer, but further, to accept the evi- dence that many other causes and agents also exist which appear able to produce these tumors." TI KU 000006584

t N Various Susj)ects in Lung Cancer (Continued f rom page 1) far reaching contentions -f•_ ade in favor of the cigarette theory of lung cancer causation read rather convincingly as long as one either does tiot know or conveniently neglects to consider crit- ically the indeed large and reliable amount of evidence that is in disagree- ment with such concepts ffered often as facts and proof." Six Reasons Out{ined They outlined six reasons why the cigarette theory of lung c incer causa- tion is not "of such overwhelming im- portance as alleged by many investi- gators": "1. The increase in the i'requency of lung cancers started on the European continent before cigarette smoking as- sumed in these countrie:; significant proportions. "2. The marked irregu arity of the lung cancer mortality ra :es, of their progression rates, and of their sex dis- tribution rates in differct t countries, different regions, and diffarent metro- politan areas of the same, ountry, mil- itates strongly against a predominant causal action of a single factor, such as cigarette smoking. °`3. The consistent discrepancy be- tween high urban lung cancer rates against low rural rates observed in several countries carries tlie same con- notation. "4. The definite differ:mces in the lung cancer rates betweexi native and immigrant whites obsened in New Zealand, South Africa, a.td Ohio de- spite presumably similar s noking hab- its does not favor the concept of a major role of cigarette smoking in the causation of lung cancer. "5. The absence of a pcsitive statis- tical relation of cigarette smoking to ' cancers of the hands anr lips which become intensely expose.l to incom- plete combustion products of cigarette tobacco represents evidence which dis- agrees with observations vlade among individuals exposed to co=i1 tar fumes and dusts and developin; cancers of the skin and lung. "6. The allegation that the almost threefold higher lung ca~lcer rate in England compared with titat found in the United States is attribiitable to the English habit of smokin; cigarettes down to a very small butt ... is based on unsuitable and, thereFore, incor- rectly interpreted statistic al data ..." The scientists also said "The volu- minous reports on this subject pub- lished during recent years give, in general, scant consideration to the in- fluence which nontobacco factors may have exerted on the causation and the rise in frequency of lung cancer, which started before cigarette smoking be- came generally popular. While it is quite likely that cigarette smoking has played a direct or indirect role in this respect, it is, on the other hand, not probable that it was of such over- whelming importance as alleged by many investigators." A Wide Range They noted that "The great number of claims concerning the predominant importance of cigarette smoking in the causation and rise in frequency of lung cancer, ranging from 60% to 96Q/o of all lung cancers in males, are evidently products of a rather selective type of research and of spurious rea- soning from a limited and special kind of evidence." Recent studies "have not confirmed the much publicized contention of a close and consistent relation of cig- arette smoking to those so-called pre- cancerous lesions," they said. "It is evident ... that many other irritants of the bronchial mucosa, and not only cigarette smoke, exert a simi- Iar effect. In fact, one investigator noted that such lesions are not infre- quently presentin children." While expressing reservations about various cigarette theories, the scien- tists added: "The type and amount of evidence on this matter on hand justi- fies the conclusion that cigarette smok- ing has contributed to or aggravated the action of other carcinogenic respi- ratory pollutants by producing espe- cially functional disturbances in the bronchial mucosa." The scientists also reported that can- cerous reactions were produced in mice subcutaneously injected with ma- terial derived from air pollutants of eight cities. They said their work was a "first and preliminary step in a prolonged and comprehensive program dealing with relationship between air pollu- tants and health hazards, including cancers." Authors of the paper were: Drs. W. C. Hueper and W. W. Payne, National Cancer Institute; Drs. P. Kotin and H. Falk, University of Southern Califor- nia, and Drs. E. Sawicki and E. C. Tabor, U. S. Public Health Service. 6 Ink Powder and Chemical Induce Animal Lung Cancers A Russian scientist, writing in a U. S. journal, reports inducing lung cancers in experimental animals with the use of a chemical carcinogen and black-ink powder.* (See Special Re- port on page 2.) Prof. L. M. Shabad said the cancers were induced in about 30 percent of rats by intratracheal intubation of 6 to 10 mg. of 7. 12-dimethylbenz(a)an- thracene with black-ink powder. The cancers, he said, were usually epidermoid carcinomas originating from metaplastic bronchial epithel- ium, but there also were some adeno- carcinomas. They were similar in many respects to primary human lung cancer, he said. Shabad said that in earlier Soviet experiments, the carcinogenic hydro- carbon alone, without black-ink pow- der, did not induce lung cancer. In the present work, he said, the powder "probably absorbed and retained the carcinogen, at least for a time. "The study of the significance of such factors of 'deposition' in the ori- gin and the pathogenesis of cancer of the lung in humans is of consider,able theoretical interest and could be of practical importance, but at the pres- ent time work on this subject is only beginning." '"Experimental cancer of the lung." Jour- nal of the National Cancer Institute, June 1962. Suicide, Cancer Death Rates Seen Linked by U. S. Data A tabulation of data from U. S. vital statistics "indicates the existence of a definite, but complex relationship between the suicide mortality rate and the cancer mortality rate in the U. S. for the years 1914 to 1953," says Dr. Lawrence LeShan, Institute of Applied Biology, New York City.* If a significant relationship does exist, he wrote, "it would, at the very least, markedly strengthen the case for the importance of psychological fac- tors in cancer mortality." He said that "it would seem as if fuller understanding of some of the variations in the cancer mortality rates must await more comprehension of the emotional life history of the can- cer patient and of the socioeconomic events which influence his psycholog- ical status." * "Cancer mortality rate." Archives of General Psychiatry, May 1962. TI KU 000006585 TIMN 0130761