Document 0qLjLVKpbZ95X4mXyV5XEODBd

FILE NAME Kent KNT DATE 1951 Mar DOC KNT124 DOCUMENT DESCRIPTION Journal Article - Cancer of the Lung in Relation to Tobacco - British Journal of Cancer Doll & Kermaway Dogs 1957 BRITISH JOURNAL OF VOL V MARCH, 1951 CANCER NO 1 CANCER OF THE LUNG IN RELATION TO TOBACCO M. E. DAFF R. DOLL AND E. L. KENNAWAY From the Pathological Department St. Bartholomew's Hospital and the Statistical Research Unit of the Medical Research Council London School of Hygiene and Tropical Medicine Received for publication February 20 1951 Further Data on the Arsenio Content of Cigarettes IN an carlier paper Daff and Kennaway 1950 data were given for the arsenic content of 5 brands of cigarettes of British and American types of 8 brands of Turkish type and of two others French Rhodesian and also for the amount of arsenic volatilized in smoking A further series of estimations of arsenic in cigarettes from 8 countries U.S.A. Canada Norway Switzerland Austria Italy Bulgaria Poland is reported in Table I. In all 27 brands have been examined All quantities of arsenic given in this paper are stated as As is numerically the same as parts per million g which The results given in this and the earlier paper show- 1 A high arsenic content 24 to 106 in 10 Turkish brands smoked in England U.S.A. Canada and Norway 2 A low arsenic content 0.0 to 3 in 8 Turkish brands as sold in England in a Rhodesian brand in a popular Austrian brand and in cigarettes from France Poland and Bulgaria 3 Intermediate amounts 3.1 to 12.0 in a less popular Austrian brand and . in cigarettes from Switzerland and Italy One Canadian brand showed a range of 8.6 to 18.7 Of course no claim is made that the analyses of these cigarettes which we have happened to obtain through the kindness of various friends can give any complete picture of the comparative habits of smokers in the different countries But most of the brands are popular ones and the results show on the whole a gradation from the arsenic American type in Western Europe to the arsenicpoor Turkish type in the East with an intermediate European zone which accords with Hutson's 1937 account of tobacco culture in Europe quoted below p 3 Cancer of the Lung in Relation to the Types of Tobacco Smoked in Various Countries Some recent investigations and especially those of Wynder and Graham 1950 and of Doll and Bradford Hill 1950 show an association between the smoking of tobacco and especially of cigarettes and cancer of the lung Since arsenic is under 1-20 , M. E. DAFF R. DOLL AND E. L. KENNAWAY TABLE Arsenic Content of Cigarettes Brand Number of cigarettes Brands other than English As-- ng per g U.S.A. U.S.A. Brand C . 2 46.4 46.7 " P.M. . 1 . 51.0 Canada Brand K . 4 36-8 58.2 47.1 55-1 " 0 . 5 8-7 18.4 8-6 18-7 9-1 W " : 6 41.1 46.5 57-9 79-5 67.5 41.7 " B.C. 3 43.5 57.6 42.5 Norway Brand B " Switzerland Brand P . Italy Brand N . Austria Brand D . M " . Poland Brand Z . Bulgaria Brand A . " . 3 71-7 65-8 74.6 4 54.4 52.4 55-6 49-7 4 ' 6-4 3-1 3.9 3.4 6 ~ 10.5 9.8 10-2 13.7 9-1 8-3 13 . 12.0 13 . Trace 2-1 0-9 5 ' 2.5 21 12 2.7 1.5 4 0-7 1-2 nil 0.3 4 . 0-6 0-6 nil 0.2 some circumstances carcinogenic in Neubauer 1947 Currie 1947 ; 1 ford Hill and Faning 1948 the question arises whether the arsenic in tol is concerned in this process Instances of cancer of the lung in workers ext to arsenic are given by the Chief Inspector of Factories 1939 In a ca 86 arsenical poisoning . . . due sodium arsenite which was fatal the mortem examination revealed that in addition to pigmentation of the trunk limbs warty growths all over the body and perforation of the nasal septum : was a primary cancer of the right lung with metastatic growths in neighbo glands and in the liver In a later Report Chief Inspector of Factories ; a 66 another case is recorded . . . in filling machine operator aged 5 43 years in a factory manufacturing sheep dip containing sodium arsenite cause of death being due to carcinoma of the right lung Three similar cas tiba tibatiba CANCER OF THE LUNG IN RELATION TO TOBACCO 3 pulmonary carcinoma occurring in arsenical sheep workers have been notified since 1939. Henry 1950 describes a case of cutaneous cancer . . in a furnaceman making sodium arsenite who eventually died of cancer of the lung " Two industrial cases of bronchial cancer are recorded in persons _ , taking arsenic medicinally over long periods Montgomery and Waisman 1941 Semon 1945 This question might be decided one could have equally reliable statistics for the incidence of cancer of the lung in countries where the pre- dominant tobacco smoked is of the arsenic or of the arsenic type We have been collecting data on this question by correspondence but this is a slow and difficult process In view of the great practical importance of the matter it seems better to publish the available data now in the hope of promoting first- hand inquiry in appropriate countries So far as we know the only statistical studies of cancer of the lung in relation to cigarette smoking which have come from any countries other than Great Britain the U.S.A. and Germany are those of Saglam 1944 from Turkey and of Dungal 1950 from Iceland The data which one would like to obtain from any given country are A. From national sources Total consumption of tobacco 2 Proportion of tobacco which is of American or Turkish type 3 Proportion of tobacco smoked as cigarettes cigars and tobacco 4 Population by ages 5 ~ Number of deaths attributed to cancer of the lung The two last items for men and women separately B. From university clinics for men and women separately by ages Number of autopsies 2 Number of autopsies showing cancer 3 Number of autopsies showing cancer of lung In the countries where A is not available one must rely on B. The ratio of 3 to B has been suggested as the most reliable index for the present purpose Heady and Kennaway 1949 Figures for a number of separate years are of course very desirable but those for the war period 1940 to 1945 generally show considerable disturbances Fig 2 5 and must be avoided We are indebted to the staffs of various Embassies in London for data on A 2 3 and 4 in addition to what can be found in such works of reference as the " Statesman's Year Book A great deal of information is given in a report The Consumption and Production of Tobacco in Europe by J. B. Hutson 1937 In such comparisons between different countries at least four possible carcino- genic factors must be considered namely : 1 Smoking of tobacco 2 Smoking of tobacco containing arsenic 3 Inhalation of the dust of towns and of coal | smoke 4 Inhalation of products of the internal combustion engine von Thus populations in eastern Europe which are subject to the first of these factors and only slightly if at all to the second will also be comparatively free from the third and fourth while the industrial peoples of Britain and the U.S.A. will be most exposed to the second third and fourth together and the inhabitants of Iceland will be subject to the second only Tobacco Culture in Europe Hutson 1937 classifies the types of tobacco grown in Europe thus : 1 Oriental Turkey Greece Bulgaria S. Yugoslavia U.S.S.R. 2 Oriental S.E. Italy S.W. Yugoslavia Rumania Hungary S. Czechoslovakia S. Poland 4 M. E. DAFF R. DOLL AND E. L. KENNAWAY 3 Dark cured Hungary Rumania Czechoslovakia Germany N. Italy France Spain Belgium Sweden Switzerland He divides the countries of Europe into 4 groups : Germany 1 Those in which a portion of the factory consumption is grown Germany Spain Belgium Poland Czechoslovakia Switzerland 2 Those in which production is approximately equal to consumption Italy Yugoslavia Rumania 3 Those which produce a surplus Greece Turkey Bulgaria Hungary 4 Those in which little or no tobacco is grown which are all those not named above The countries in the third group are of most interest if one can assume that the tobacco smoked there is at any rate very largely of the arsenic type but unfortunately the conditions for the study of cancer of the lung in the whole population are not as yet very favourable in them and this subject like that of cancer of the liver presents peculiar difficulties on account of the danger of confusion of primary and secondary growths Tobacco Consumption and Cancer of the Lung in Various Countries Turkey 1 Data on the consumption of tobacco in Turkey are given in Table II TABLE Consumption of Tobacco in Turkey Year 1925 Tobacco consumption million lb. 15.8 . Population 13,023,000 Tobacco consumption lb. per head . 1.21 1930 21.9 . 14,591,000 : 1.50 1935 25.0 . 16,158,018 : 1.55 1937 28.2 : 16,800,000 . 1-68 1942 37.21 , 17,820,950 . 2.09 1947 40.7+ 40.7+ . 18,870,785 . 2.16 1949 39.7+ . 20,900,009 * Figures from Hutson 1937 Figures provided by the Turkish Embassy t The Times October 30 1950 1.90 2 Prof. Schwartz of the University of Istanbul writes that in Turkey tobacco is consumed almost wholly in the form of cigarettes that cigars European pipes and the oriental water are almost unknown among the bulk of the people and that there are many heavy smokers among women 3 The only publication from any Balkan country upon cancer of the lung in relation to smoking appears to be that of Prof. Saglam 1944 of the University of Istanbul who gives the following details which are quoted in full in view of the importance of his original paper and the difficulty of access to it The clinical statistics of pulmonary carcinoma in Turkey : The Int Clinic of Gulhane Suleyman Numan The Int Clinic of Gulhane Tevfik Saglam . The Sect for Int Diseases of Gureba Tevfik Year 1899-1908 1923-1926 Number of patients . 4270 . 2343 . Pulmonary tumour 2 . 7 Rato per thousand 0.46 47 2.1 3.0 Saglam . : . : : - 1931-32 . 1459 9 . 7 2 Haydarpaxa Numune Hast Tevfik Saglam . 1936-1939 . 4230 . 24 5.6 7 * Recalculated from the figures given by Prof. Saglam in the two adjacent columns CANCER OF THE LUNG IN RELATION TO TOBACCO The pathologic statistics : Year . Number of Pulmonary autopsies cancer Gulhane Reinhard . . . 1899-1908 . 800 . 3 . Gulhane Lufti - : . . : 1923-1926 . 502 . 5 : Haydarpasa Numune Hast . . . . 1936-1939 . 635 . 14 . The pathologic Institute of the Uni- versity of Istanbul Prof. Ph Schwartz 1935-1943 5126 79 . Rato por thousand 3.7 10 22 15.4 Taking the clinical statistics into consideration it is clear that within 30-40 years the increase in our clinics is 12 times and according to the anatomo logic statistics it is 4.1 times as much We have seen 11 cases of pulmonary carcinoma in the newly inaugurated ae 3. Ic Hastaliklari Klinigi in 23 months among 2084 patients 5-3 in a thousand All these statistics show that in our country within the last 30 years pul- ore monary carcinoma has increased in a great proportion Saglam rejects cigarette as a factor in the incidence of bronchial carcinoma Some authors believe that there exists a relationship between Rt smoking tobacco and inhaling the smoke and pulmonary carcinoma Animal experiments seem to support this point of view Some authors are of the opinion aE that especially cigarettes play a great part in its production We do not hold the same view For a long time at least since 50 years almost only cigarettes are smoked in our country In spite of this the increase in pulmonary Ca. in this country has gone on the same pace as in those countries where cigars and pipes are mostly smoked The amount of tobacco consumed in our country has shown a constant increase and from 9,370,000 kgr in 1926 has risen to 16,680,000 kgr in 1942. But this rise is not sufficient to explain the increase in pulmonary Ca. But there is no exact basis for any such argument We do not yet know what consumption of any tobacco produces any given incidence of bronchial carcinoma nor do we know the relations of any such effect 4 We are indebted to Prof. Saglam Prof. Schwartz and Dr. Yenermen for a full protocols of the 193 autopsies on cases of primary tumour of the lung carried out at the University of Istanbul during 1934-1950 and b figures for the total autopsies and autopsies on cases of cancer by sexes for the same period Table III To make the material comparable with other series we have omitted the TABLE Cases of Cancer of the Lung Among Autopsies Carried Out at the University of Istanbul 1935-1950 Period All cases Number of autopsies All cancer . Cancer of lung Malo Fomule Total Male Female Total Male Female Total 1935-9 1833 947 2780 . 217 97 314 . 33 5 38 1940-4 2585 747 3332 302 70 372 . 48 7 55 1945-9 , 2612 1323 3935 359 129 488 : 73 10 83 1949-80 . 767 488 1255 . 104 53 157 . 31 q 35 Changes in incidence will be seen more clearly in Table IX whore cases of cancer of the lung are shown as percentages of all autopsios and of all cancers twice Note that data for the year 1949 appear : 6 M. E. DAFF R. DOLL AND E. L. KENNAWAY data for 1934 and have removed 3 cases all in men described from the total of as benign tumours and primary lung tumours a chondroma in 1935 another in 1939 a polyp in 1937 We have however retained four cases described histo- logically as not being carcinoma namely lymphogranuloma in a man one case each in 1936 and 1937 sarcoma in a man 1941 cylindroma in a woman 1942 Bulgaria and Greece Hutson 1937 states that the surplus produced in Bulgaria and Greece with that from Turkey and Hungary makes up the bulk of the world's of oriental cigarette tobacco supply It is difficult to estimate the amount consumed locally as an unknown amount is grown for personal use and escapes tax The official figures man's Year for tobacco consumption Hutson 1937 and for population ,, States- Book 1931 indicate an annual consumption of about 1.7 lb. head in Greece and of 1.9 lb. per head in Bulgaria in the period 1925 to per 1930. The figures are similar to those obtained for Turkey in 1937 1-68 lb. per head Table II We have no data on the incidence of cancer of the lung in these countries Yugoslavia We do not know the amount of tobacco consumed in Yugoslavia Kosir of Ljubljana has provided us with information Yugoslavia but Dr. of the population He writes that the kinds of about the smoking habits 56 are tobacco smoked in Yugoslavia : a type Makedonija cigarettes ; b type Hercegovina cigarettes ; and c type Vojcodina pipe and cigars There are smoked principally cigarettes These are of the oriental i.e. they have a natural ' bouquet which gives the tobacco type - + Only in the western part of Yugoslavia there tayrpeesMmaokkeeddocniigjaras and pipe Use of tobacco for snuffing is quite insignificant Before the last war the only import was some Dutch tobacco for cigars ; during the war some Bulgarian and after it some American tobacco through U.N.R.R.A. was imported but all these amounts were very small We are also indebted to Dr. Kosir and to Prof. F. Hribar for a statement of the numbers of autopsies and of those on all cases of cancer of the lung by sex carried out at the malignant disease and of Clinical Slovenia during 1925 to 1949. Hospital Ljubljana These data are shown in Table IV Table Cases of Cancer of the Lung Among Autopsies Carried Out at the Clinical Hospital Ljubljana 1925 to 1949 Period 1925-9 1930-4 . 1935-9 1940-4 . 1945-9 . 1948-9 All cases Male 564 793 1003 1080 1929 897 Female 553 765 868 1050 1589 791 Number of autopsies oO ~ Total 1117 . 1558 : 1931 . 2130 . 3518 1688 . All cancer Male 72 117 132 129 246 141 Female Total . 65 91 113 135 137 208 . 245 . 264 . 292 538 : 154 295 : Cancer of lung Male Female Total 8 21161 10 5 21 61 6 11 21161 12 18 21161 19 28 9 38 19 7 26 See footnote to Table III CANCER OF THE LUNG IN RELATION TO TOBACCO Switzerland 1 We are indebted to the Bureau F^'d^'ralde Statistique for information about the amount of tobacco consumed over the period 1936 to 1949 and to the Direction G^'n^'radles Douanes for information about the sources of imported tobacco The data are summarized in Table V and Fig 1 TABLE Consumption and Sources of Tobacco in Switzerland 1936 to 1949 Percentage of tobacco Year . 1936 1937 1940 1943 1945 1947 1949 Tobacco consumption lb. por head 3.5 4.0 4.6 4.9 5.9 5.7 4.5 grown Imported from / Balkans U.S.A. U.S.A. Other Other arous 38 6 10 . . . 46 12 12 Pew , ' 18 : oe : .- : 20 See 19 18 . - : .- : o . dd. 42. 28 * Mainly Brazil and the East Indies We have no detailed information about the manner in which the tobacco is smoked but until World War II cigarettes formed only small proportion of the whole Table X 2 Prof. H. v Meyenberg has provided a summary of the autopsies performed at the Pathological Institute Z^...richduring the period 1927 to 1941. Among 20.681 autopsies there were 3584 cases of cancer and 276 cases of cancer of the lung These figures are compared with those from other countries in Table IX 3 It is however not necessary to be dependent on hospital statistics for an estimate of the incidence of cancer of the lung in Switzerland as vital statistics are available for the whole country We are indebted to the Bureau F^'d^'radle Statistique Berne for a statement showing the deaths attributed to cancer of the bronchi and lungs by sex for each year 1929 to 1949 Fig 1 and also for data on age distribution of the population The crude death rates shown in Table X in comparison with the rates from England and Wales and from Norway have been calculated from population statistics provided by Stocks personal communication Norway 1 Prof. Leiv Kreyberg of the University of Oslo has supplied figures for the production of tobacco pipe cigars and cigarettes for each year 1930 to 1947 Fig 2 and for selected years in Table VI " Mr. O. Jakobsen of the Norwegian Embassy writes that Norway normally AN imports 85 per cent of her tobacco from America Virginian tobacco 9 per cent from the Middle East Turkish tobacco and 6 per cent from elsewhere The imports are practically equal to the consumption as the only exports are to the AT mercantile marine Tobacco except cigars is almost all imported as such and not as cigarettes Many persons buy the cheaper pipe tobacco and make their own cigarettes obtaining thus nearly twice as many for a given sum ; hence the 8 M. E. DAFF R. DOLL AND E. L. KENNAWAY 500 Males 400 200- Tobacco @, if 1 , ' f 2 s Females FIG Cancer of lung 1929 1935 i 1947 i ty 1929 1931 1933 1935 1937 1939 1941 1943 1945 1947 1949 Deaths 1929-1949 Consumption of tobacco hundred thousand pounds 1936-1949 Switzerland official figures for the consumption of pipe tobacco and smoking is most common in rural cigarettes are misleading areas Table Consumption of Various Types of Tobacco in Norway Kreyberg 1931 to 1947 Year Year I I I I I I 1946 1947 Tobacco consumption TUTT TUTT TUTT I TUTT 1.4 TUTT TUTT TUTT 1.0 TUTT 2.9 Percentage of tobacco in form of : TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT TUTT 44 . TUTT tobacco TUTT TUTT TUTT TUTT TUTT TUTT TUTT 55 2 Prof. Leiv Kreyberg has supplied figures for the deaths attributed cancer of the lung by sex for the years 1930 to 1948 to Fig 2 3 for deaths sepa- CANCER OF THE LUNG IN RELATION TO TOBACCO % X. rately in urban and rural areas and for the population by sex The calculated death rates from cancer of the lung are shown in Table The national figures are reasonably reliable as according to Mr. Jakobsen The doctor who has treated the deceased during his last illness is required to fill in an official certificate stating the cause of death . . . which must be stated in medical terms as precisely as possible and it is not permitted to use general diagnoses such as " disease of the heart or " disease of the lungs The 160 Deaths Cancer Cancer of lung 1930 trite sists 1930 1932 1934 1936 1938 1940 1942 1944 1946 1948 FIG Cancer of lung Deaths Consumption of tobacco hundred metric tons Norway 1930 1947 Kreyberg statement must be in accordance with an official nomenclature of causes of death _, The doctor is required to examine the patient after death 3 Twenty per cent of the population were estimated to live in the citics of Norway in both 1930 and 1946 ; the proportion living in urban areas can therefore be considered to have been constant throughout the period under review The following are the estimated crude death rates for each sex in urban and rural areas Norway Death Rates of Cancer of Lung per million Death rates of cancer of lung per million 1930-38 . 1939-47 Urban Male Female . 24 . 19 . 63 42 Persons 21 52 . Male 14 30 Rural Female 12 24 Persons 13 27 10 M. E. DAFF R. DOLL AND E. L. KENNAWAY The data show that a The incidence is greater in urban areas b The urban excess is slightly greater for men than for women- 1930 38urban : rural ratio male 7 ; female 1-6 1 1939-47 " >> male 2 , female 8 c The increase between 1930 and 1947 has been the country and greater for men than for greater in the towns than in women Urban increase male 2.6 1 female 2.2 1 Rural " male 211 211 female 2-0 1 Males Females Females = metre att SpAetre ee. Fs; SIEV Lotit tite det py 1 1930 1932 1934 1936 1938 1940 1942 1944 1946 1948 FIG Cancer of lung Deaths Norway 1930-1947 Kr^,yberg Sweden . Snuff used for chewing and for insufflation makes ing proportion of all the tobacco up a very large but diminish- products consumed Hutson 1937 Prof. Elis Berven personal communication Table VII Prof. Berven " very fine powder like the English snuff and is inhaled in writes Snuff is a the nose For chewing there are two small quantities through types a The same type of snuff 3-4 big pinchlip es i.e. about onmandiblee teaspoonful taken from the snuff is put in between a tough mass in size of about backwards and forwards until it becomes hours . . a hazel which is lying at the same place about b Chewing tobacco is to be had in the form of braids CANCER OF THE LUNG IN RELATION TO TOBACCO 11 Table Distribution of Different Kinds of Tobacco as Per Cent of the Total Consumption Sweden Berven personal communication Cigars and Tobacco Tobacco Consumption a Year cigar Cigarettes for for Snuff Tobacco lb. per head per year : rettes smoking chewing head Snuff Tobacco % % % % a 1908 . 10.8 3.3 4.4 7.9 0.7 a 1921 . 10.1 8.3 11.1 3.0 33.1 1 a 1931 9.3 1.2 i 1936 8.5 16.1 22.3 13.0 15.5 1.8 1.2 40.2 1.73 47.5 47.5 1.55 1.4 1944 6.7 27.9 23.7 0.6 1948 5.1 44.9 16.3 0.4 33.3 16.1 47.5 1.061.061.5 17 1949 4-7 46.9 15.6 0.4 32.4 2.1 from which they bite 1 to 2 cm This piece is chewed to a half consistence which is then lying at the same place as the snuff Unfortunately no figures for the incidence of cancer of the lung are available Iceland Smoking habits in Iceland are discussed by Dungal 1950 according to whom " The consumption of tobacco particularly in the form of cigarettes has certainly TEATS been much less in Iceland than in most European countries and America Dungal's figures for cigarette consumption and for the incidence of lung carcinoma are summarized in Table IX Britain - Data with regard to tobacco consumption and the incidence of cancer of the St lung in Britain have been presented previously Kennaway and Kennaway 1947 ; St Fig 4 5 New data on the autopsy incidence of cancer of the lung in British hospitals have been collected Table VIII ESOS TABLE Cases of Cancer of the Lung Among Autopsies Performed at Three CURE British Hospitals 1925 48 et Hospital Period All cases Number of autopsies All cancers Cancer of the lung Glasgow Western Infirmary Cappell St. Mary's London Newcomb St. Bartholomew's London Cunningham 1925-9 1930-4 1935-9 1940-4 1945-8 . 1947-8 1930-4 1935-9 1940-4 1945-8 1947-8 1930-4 1935-9 1940-4 1945-8 | 1947-8 . M. .. te . oe 827 746442 F. Total .. 481 746442 1154 1214 1395 . 1273 1324 . 687 . 1308 1188 683 371 1056 987 428 229 558 528 I111 600 1614 1515 544 761 301 125 426 M. 133 F. Total 83 216 = M. . 2878588 Burggan0 235 2878588 Burggan0 190 124 314 . 2878588 Burg an0 180 124 304 . 2878588 Burggan0 220 133 353 . 2878588 Burggan0 103 68 171 . 2878588 Burg an0 140 2878588 Burggan0 171 112 283 2878588 Total 34 10962837 10962837 = 10962837 10962837 10962837 10962837 10962837 139 83 206 192 90 47 95 121 229 130 301 313 7865 0032 9825 7865 0032 9825 7865 0032 9825 7865 10 9825 Ili 60 171 60 27 87 753 27 88 753 27 88 * See also Table IX 12 M. E. DAFF R. DOLL AND E. L. KENNAWAY 10000 Males 8000- 6000 4000 = ~ oe0-e* Tobacco 0 : x he . Females Lite dt tite te ty ta ta ba be a i 1924 1926 1928 1930 1932 1934 1936 1938 1940 1942 1944 1946 1948 1950 FIG Cancer of lung Deaths England and Wales Consumption of tobacco hundred thousand pounds United Kingdom 1924 1949 bj- * i \ e o rtae Pec FIG 1924 jp td 1924 25 26 27 28 29 30 31 32 33 34 35 36 38 39 40 41 42 43 44 45 46 47 48 49 Consumption of tobacco Ib per head United Kingdom Switzerland and Norway o-- _@ @ United Kingdom @---@.--+@ Switzerland ^ Norway CANCER OF THE LUNG IN RELATION TO TOBACCO Incidence of Lung Cancer Comparison of the data from various countries In Table IX hospital data from five sources in Britain and from Turkey Yugoslavia Switzerland and Iceland are presented together The cases of lung cancer are shown as percentages of the number of autopsies and of the number of malignant growths found at autopsy ; sexes are shown separately whenever the data are available For comparison estimations of the annual consumption of tobacco are included The data show that : 1 A high proportion of autopsies on cases of cancer between a fifth and a third are now found to show cancer of the lung in British hospitals ; 20 years ago the figure was between 10 and 15 per cent 2 The experience concerning males in Istanbul in recent years is not unlike < be: the 3 BriTtihseh eexxppeerriieennccee in Slovenia is comparable with British experience in the first quarter of this century 4 The lowest recorded figures are found in Iceland 5 Swiss figures are comparable with Slovene ones Swiss national statistics however indicate a higher incidence Table X and too much significance should * not be attached to one hospital series Table X shows the crude death rates from cancer of the lung in England and i Wales Switzerland and Norway for selected years between 1931 and 1947 and estimates of the annual rates of consumption of tobacco s A comparison of the distribution in the three countries is given below * Mr. Olaf Jakobsen has kindly supplied figures for Norway by sexes for 1930 and : 1946 the figures for the latter year are summarized in the table The data for Switzerland were supplied by the Bureau F^'d^'radle Statistique Berne : Population Per cent of all ages All 203040506070- TIT England and TIT TIT TIT TIT TIT TIT TIT TIT TIT TIT TIT TIT TIT TIT TIT 6.6 TIT TIT TIT ~ TIT TIT TIT TIT . TIT - 7.2 . 7-1 . TIT . TIT . TIT . All 2030 40 506070- Females England and Wales 1947 51-6 7.5 7.9 7.5 6.3 5.0 3.8 Norway 1946 50.7 8.3 7.9 7.0 5.4 3.9 3.5 ~ Switzerland 1950 51.7 7.5 7.3 7-7 6.2 4.5 3.4 Males of the important group 50 to 69 make up a rather larger percentage of the population in England and Wales 9-3 than in Norway 8.3 while the position of Switzerland is intermediate 9.0 these small differences cannot account for the differences in the death and justify the use of crude death " rates 14 : S| A<fs i Pe: a = 8 a Qal . ditaeycoa5"4 {. eo (6-0 (eS (6-2 . (oe * quasfiqn we (pey (ey) sso) 's93) SO) ) 0-0 eo eaSo) uondmsuoyenuy eEC }Se oO wet us a, s Ue red a 6-8 _ a * : 7 7. . o - - ( FF (9 89) oy q]) 7 LL U2 BS Ge ) ) : sit{er879361 Le-986T ogtrae Bru osuqo4 aoe 2867 2L6P16L Ok6T E16 geet | eper Asdomp - * 7 * - ; , ; ; : = 7 . . , b: . = "' yw ; of Per Autopsies All Diagnosed as Al in All Autopsies Autopsies Autopsies and Compared with Cancer Tobaco Consumption Diagnosed Diagnosaed t Autopsy Autopsy Autopsy in Diferent 9-8 828 88 CancerCancer Countries Difernt ? o ngay JO ~ Locality quedo Period Period = autopsies autopsies autopsies .. autopsies 0-8 6-8 2ST Al:l cancer cancer autopsies autopsies 1-& TI 6-0 tobaco tobaco consumption 3: consumption 8t BBE 14 19 -1923 303 0.96 bus Jed 1894-1918 Holmes 1894-198 Holmes ) 1919-1923 - a fo Holmes * ; * : 6-3 8-BO 0.96 -1.16 " 9-6 $61 * . tro SST 6ST #:0Z * * a -81906-08 1906-08 , . 1923-25 , bes cgts T-0 kee : } G1 GrGT <: 83 8-8 GL G:F 86 est SAOUIVD o Infirmary Infirmary Jo InfirmayCIanpfiremlay saidogne 11994205--4291935-39 $<-180 PIBONZVAUL ) 19 3-1937 2.4 93-137 IT-@ 1930-34 16.5 2 0- U<s PP 2-.9 2.9 tr fF 16.5 16.5 16.5 14.5 14.5 1% 15.7 6-0 9-0 6-0 Et 1934 36 9-0 8-s 8-F 8-9 8% oT 2.9 OF 1940-4 1945-48 a 24.1 7 - 4.4 .4 - 6-1 % 24.1 24.1 9-4 14.3 14.3 $0 20.4 1-0 T-0 T-0 1946 47,5 3 AOZOL ) 93 BE 8-0 6-0 3 London [Ty 1935-39 LondonNewcomb Bartholmew's Cuningham Bartholomew's 1940-4 1940-4 7 - "* . - - 8% a &9 PS L- 29.5 29.5 8.9 83 21.4 21.4 OT LT 21 . . "+ 4.3 8.9 . " * 7 * * * * o* 19.3 * 8.2 * 15.0 * * * * ee - .* 69 8 T-P UG * * * ) * gp-oEer 1945-836I-FZ6T 1.87.9 Cuningham Cuningham 1940-4 Saglam poneg 1945-48 1935-39 358-8.7 GF -#806F4.64.6 7.07.0-POF6TSEFSET 115.52.238.7 16.716.7SEI 31.031.06-GE6T$P-ORGT1937 1.7 gp-zear SP-LEGIBeLre StPEL O8-6FET G6b-8FGT - * 14.8 Saglam pe-ogT* : 2.1 7.8 Schwartz Hribar 2.8 1935-91930-341925-29 1935-39 17.0 3.1 (iedeg) 0.9 s, 0.7 7.2 MOUTpyIBE 14.0 (anquesy) smautopzeg 0.6 XJ Agiyraoy 11994455--44991945-49 [esuoy1.7 moBsepy 1.1 speT 1 .8 0.7 ees 3.1 ~peanyso8n7.1 1936 Meynburg 11927-4927-41 Ig 4g Rays, 4 + * . : * *(ye8unq) AYULYUpendsopy , * . s ' , cgtsyravlysey ULDIAATW1,9A-raeyyag KENAWYpnqueys n1ajs06nwavliqnlyT KENNAWAY x M. F. Persons Persons consumption consumption M. Persons consumption (9-0 91 91 (20 8 " 2.8 2.8 94 94 32 7 83580) 16116132 7 131131 }6T 38)40T )9o8 162 637 FT }ez2 1 5 206 * ( cgts . 6 AUNION uorptu398 183 ~ PUS 78 figures figures available United and United smoking habits habits habits GE TE 6t BB Scotland Scotland Scotland Scotland Fe TE 68 SP and Northern Northern Northern the this by Estimated of Disturbed importance available war . 8 83 1 68 cP 9 183 . Ireland importance O44 PUDLIBZNgG PULTAUGimportance saurog eEs7D . (F-1 An ual and Wales England Wales Wales fo uordnsuo*(pey/*q) Ireland 09807 pe.sqyT jenuy (-s61) 4pu4n ttGEOF G&6T 9 }6-7 Northern Northern Northern OIrJeland Ireland 2g Oso'e 6Et'ogg't 43,050 204-DIe *8129) United Kingdom Kingdom oN * . . * - " * punpbury "UodnsUog KingdomJuevpI ponup) dunjuoTpit "Sos, PFOF 89g "Tb 96$0901 PUB : . . puez7img ur sy} aed oC) AIOA . GD0Nqo,y UIOPUIY buny seqvr JOU Jo aor LT 61 13 61 1g e9 P<e : Joueg ayy YyIn anueqiodunPep] fo prtmdulog (ecsydo) O (g-ps480) WISTWIONeoUsayip tmopsury ssaay0ouyny SQ]RAL penuy09809 (pey!: )or OdBqO}PURLOIT wosf 4 ye(T Ke1" 99 eo 98 760 6 8 ett Zot LLU esl - * * uot (eS(8S(08 " US OU a BE av Ze ee F | (eg 4 4 pg * " * - OI OY} ou 04 Jo st TOFOI Pus IOZ sig pue[siy pueyogWNIOTYTDIO poyrug, puBpoag woliut SUOIT PUR BUN sly zed ; 4g oS CTE ODT 181 $LI 90% gas ul caem . PULsugy O[GEPLeAs uoMpndo JO ce 1g ve SF ct ss 09 th SL Aq yoag- X syqey N soyez e173 . poqangsiq o[qeyas TIAN tevue) saINBYSupours YyECT W gg 6raat tet BES 13E 99886 yo CU, ques yon, + + "180% 1861 Zeer 9 <6lLE6I Orel SP6l 9PG6I LGI oy sed 16 M. E. DAFF R. DOLL AND E. L. KENNAWAY The data show that 1 The apparent incidence of cancer of the lung is increasing in both sexes in all three countries 2 The rate of increase in the 10 years 1936-7 to 1946-7 has been much the same in the three countries ; in the five years 1931-2 to 1936-7 it was more rapid in Norway than in England and Wales and was slowest in Switzerland 1931-2 . 1936 7 . 1936-7 : 1946-7 . Death Rate from Cancer of the Lung 1936-7 as percentage of 1931 2 England and Wales M. 100 170 F. Persons 100 100 . 137 162 : Switzerland M. F. Persons 100 100 100 . 141 111 132 . M. 100 177 100 252 100 173 1946-7 as porcentage of 1936 7 100 : 100 100 100 . 227 . 200 175 196 . 100 215 Norway . F. Persons 100 211 100 187 100 190 100 202 3 The rate of increase has been greater for males than for females in England and Wales and in Switzerland 4 The incidence is comparatively low in Norway In 1947 the crude death rate was approximately the same as it had been in England and Wales and in Switzerland 16 years previously Population both sexes producing one death from cancer of the lung 1931 1947 Norway : . . . . . Switzerland . . . . . . England and Wales . . . . 83,300 . 24,400 : 17,500 . 20,800 9,400 4,400 5 The difference is essentially a difference of incidence in men The inci- dence in women is similar in Norway and Switzerland and about twice as great in England and Wales Table X The incidence of cancer of the lung is much more nearly equal in the two sexes in Norway than it is in the other countries which have been studied Death rate from cancer of the lung in women as percentage of the death rate in men 1947 Norway . . . . England and Wales . . Switzerland . . . . 71 20 % The ratios of cancer of the lung in women to total autopsies in women also indicates a relatively low incidence in women in Turkey and Yugoslavia Table IX CANCER OF THE LUNG IN RELATION TO TOBACCO AS EER SEGAL The relation between increases in the consumption of tobacco and in cancer of the lung Sets , One should perhaps refer again though there may be no need to do so to the absence of any necessary connection between two quantities which are varying in the same way ; thus wireless licences in this country have multiplied at a rate very similar to that showbny cancer of the lung Kennaway and Kennaway 1947 In Tables XI and XII comparisons are attempted of data from this country Norway and Switzerland during three periods 1931-2 1936-7 and 1946-7 TABLE Comparison between Tobacco Consumption Cigarette Consumption and Death Rate Persons from Cancer of the Lung at Different Periods Country England and Wales Switzerland . Norway . . Tobacco consumption lb. per head Cigarette consumption lb. por head 1946-7 as percentage of 1936 7 . . 128 . 145 . . 155 . 170 , . . 153 . 185 . Death rate from cancer of the lung 227 196 202 < 1936-7 as percentage of 1931 2 be England and Wales . 120 . 123 . 162 Norway . . . 129 . 130 . 187 * 1949 as percentage of 1939 \ In all three countries the increase in cancer of the lung was greater than the increase in tobacco consumption between 1931-2 and 1936-7 and between 1936-7 and 1946-7 The increase in consumption of cigarettes was more like the increase in lung cancer over the later period but there was a considerable gap between the figures in England and Wales TABLE Comparison between Tobacco Consumption Cigarette Consumption and Death Rate Persons from Cancer of the Lung in England and Wales and Norway and in England and Wales and Switzerland Period Tobacco consumption lb. per head Cigarette consumption lb. per head England and Wales as percentage of Norway Death rate from cancer of the lung 1946-7 . . : 180 . 350 . 499 1936-7 . . 190 . 440 444 1931-2 . 232 470 . 513 1946-7 1936-7 England and Wales as percentage of Switzerland 085 162 . . . . . 1949 266 104 . . . . . 1939 205 179 The difference in death rates between England and Wales and Norway was also very much greater than the difference in tobacco consumption; it was 2 18 M. E. DAFF R. DOLL AND E. L. KENNAWAY however reasonably close to the difference in cigarette consumption In Switzerland tobacco consumption was much the same as in England and Wales but death rates were only half as high Differences in cigarette consumption again agree with the differences in death rates better than do differences in total tobacco con- England sumption This is because a much smaller proportion of the tobacco is consumed in the form of cigarettes in Switzerland than in available Clearly no exact proportionality has been found in the data so far between the amount of tobacco smoked and the prevalence of cancer of the lung in different countries and at different periods Cancer of the lung appears to increase more rapidly than does the use of tobacco ; such a change in effect may occur at a certain level in the dosage of a drug A complicating factor is that when the population of a country consumes more tobacco one does not know how much of this is due to the initiation of new smokers and how much to the increased use of tobacco by those who smoke already DISCUSSION 1 The high proportion of cancer of the lung found among autopsies on cases of malignant disease in males in Istanbul suffices to show that the arsenic content of tobacco has not provided any simple and exclusive explanation of the asso- ciation between cigarette smoking and this form of cancer It is perhaps too soon to say that arsenic is quite unobjectionable in tobacco for we have no information about the minimum effective dose of any carcinogen in man nor about the possible summation of effect of different carcinogens As yet we have autopsy figures only from a single centre in Turkey and of course more data from this and other sources in Greece and Bulgaria for instance TE are very desirable The figures from a single hospital in Yugoslavia suggest an incidence of cancer of the lung comparable to the British figures of 30 years ago We have no figures for the incidence of cancer of the lung upon the whole popula- ER tion of any East European country The official figures for the consumption ye of -grown tobacco are liable to the error that a portion may escape record secs 2 We do not know whether tobacco smoke itself contains some carcinogen or whether the practice of smoking renders the respiratory tract more susceptible to agents from external e.g. the benzpyrone of smoke or internal sources If the carcinogen is in the tobacco smoke and is in particulate form we facilitate its penetration to the bronchi by inhalation through the mouth thus evading the nasal filter The evidence available at the moment is against the direct car- cinogenic importance of tobacco smoke because it tends to exclude the two most obvious carcinogens arsenic and benzpyrene which one might expect to be present But the range of chemical structure of known carcinogens is now so wide that one must consider other possibilities 3 All the older data about cancer of the lung must be reviewed in the light of this connection with smoking ; one must reconsider the inverse relationship with sunlight Stocks 1947 and the very low incidence upon a rather curious assortment of occupations namely agriculture mining and spinning Kennaway and Kennaway 1947 The miner who works ground cannot smoke during third of the day and the spinner and those in many other occupations cannot smoke while at work 4 The incidence of cancer of the lung in Switzerland and in Istanbul where comparatively little smoke would be expected is against the importance of CANCER OF THE LUNG IN RELATION TO TOBACCO 19 of this factor but in this country Stocks 1936 Kennaway and Kennaway 1947 and in Norway see above the mortality is higher in towns than in the country In all such comparisons one must consider at least three possible factors namely a smoking habits b facilities for diagnosis and treatment and c atmospheric pollution with products of the combustion of coal tar or of the internal combustion engine 5 The indication that cigarettes are more active than cigars and pipe tobacco in relation to cancer of the lung raises the question whether this difference is due a to the method of combustion or b to some property of cigarette tobacco One cannot answer this question at present but it is especially important in countries where smokers buy the cheaper pipe tobacco to make their own cigarettes In Norway one obtains in this way nearly twice as many cigarettes for a given sum Jakobsen personal communication One must consider three possibilities : 1 Pipe tobacco smoked in pipes 2 pipe tobacco smoked in cigarettes ; 3 cigarette tobacco smoked in cigarettes 6 The data given and discussed above from this country Norway and Switzerland show that the study of the relations of national consumption of tobacco and national incidence of cancer of the lung has scarcely begun SUMMARY 1 Estimations of arsenic in cigarettes from the United States Canada England Norway France Switzerland Italy Austria Poland and Bulgaria show on the whole a transition from the arsenic American type in the West to the arsenic Turkish type in the East ; the latter is of course smoked in Western countries also Grec 2 In Yugoslavia Turkey Greece and Bulgaria the tobacco consumed is almost wholly grown of Turkish type type and in the form of cigarettes 3 The high incidence of cancer of the lung at autopsy in one centre Istanbul in country where Turkish tobacco is smoked almost exclusively shows that the arsenic content of tobacco has not provided any simple and exclusive explanation of the association between cigarette smoking and this form of cancer Cancer of the lung appears to be much less frequent at a centre in Yugoslavia Ljubljana than at Istanbul More information from these and other Balkan countries is very desirable 4 Norway imports about 85 per cent of the tobacco consumed from the U.S.A. and 9 per cent from the Balkan countries The incidence of cancer of the lung upon the two sexes is not very different death rate male to female 0-7 is greater in urban than in rural districts and this difference is greater in men than in women The increase in mortality in the last 20 years has been greater in men than in women and greater in the towns than in the country 5 In Sweden snuff makes up a much larger fraction third in 1949 of the total tobacco products consumed than is recorded in other countries 6 A comparison is made of the data available for the increases since 1931 in a deaths attributed to cancer of the lung and b in the consumption of tobacco in England and Wales Norway and Switzerland The consumption of tobacco per head has been for the last 10 years rather higher in Switzerland than in the United Kingdom and in Norway has been about half that in the other two - countries while the crude death rates at the beginning and end of the period were 20 M. E. DAFF R. DOLL AND E. L. KENNAWAY roughly in the proportion of 10 England and Wales to 5 Switzerland and 2 Norway Cigarette consumption was approximately in the proportion of 4 England and Wales to 2 Switzerland and 1 NorwayNorway and was more in accord with the relative death rates The increase in the number of deaths has been about the same twofold in all three countries but the increase in consumption of tobacco | and cigarettes has been less The differences in the incidence of cancer of the lung are therefore quite different in extent from those in the quantity of tobacco consumed ; they are more like though still different from those in the quantity of cigarettes consumed The study of the relation between the national con- sumption of tobacco and the national incidence of cancer of the lung has scarcely begun We wish to thank Prof. Saglam and Prof. P. Schwartz of the University of Istanbul and Prof. Hribar Director of the Institute of Pathological Anatomy and Dr. A. Kosir of the Clinical Hospital Ljubljana for their generosity in allowing us to use their very valuable records We are indebted to Prof. Leiv Kreyberg of Oslo Mr. Olaf Jakobsen of the Norwegian Embassy Prof. H. R. Schinz of the Kantonspital Z^...richProf. H. v Meyenburg of the Pathological Institute Z^...richMr. S. T. Hisim of the Turkish Embassy Mr. Popov of the Bulgarian Legation Prof. Elis Berven of Stockholm Prof. H. E. Rawlinson of the University of Alberta the Bureau F^'d^'ralde Statistique Berne and the Direction G^'n^'radles Douanes Berne for their kindness in supplying us with statistical and other material In this country we have to thank Dr. G. J. Cunningham Prof. D. F. Cappell Prof. A. Bradford Hill Prof. W. Newcomb Dr. C. C. Spicer Dr. Percy Stocks Mr. H. L. Henderson Mr. R. E. Waller and Miss Mary Atkin for help in various ways We wish to express our gratitude to the British Empire Cancer Campaign and the Anna Fuller Fund for generous grants REFERENCES Bradford A. and Faning E. 1948 Brit J. indust Chief Inspector of Factories and Workshops Ann Rep Stationery Office 1943 Ibid p 45 CURRIE A. 1947 Brit med Bull 4 402 Med p 22. 5 2 London H.M. DAFF M. E. AND KENNAWAY E. 1950 Brit J. Cancer 4 173 DOLL R. AND BRADFORD 1950 Brit med J. i 739 DUNGAL 1950 Lancet ii 245 HEADY J. A. AND KENNAWAY E. .- 1949 Brit J. Cancer 3 311 HENRY S. 1950 Ann Roy Coll Surg England 7 425 HUTSON J. B.- 1937 U.S. Dept. of Agric Technical Bulletin No. 587 KENNAWAY E. L. AND KENNAWAY N. 1947 Brit J. Cancer 1 260 MONTGOMERY H. AND WAISMAN 1941 J. Invest Derm 4 365 NEUBAUER 1947 Brit J. Cancer 1 192 SAGLAM 1944 Bull Fac Med Istanbul Yil 7 Sayi 2 Imumi No. 28 Nisan- Haziran 1944 p 3793 128 SEMON H. 1945 Proc Roy Soc Med 38 Section of Dermatology STOCKS 1936 Ann Rep Brit Emp Cancer Camp 13 1947 Difernces Studies on Medical and Population Subjects No. 1. Regional and Local Differences in Cancer Death Rates London H.M. Stationery Office WYNDER E. L. AND GRAHAM E. 1950 J. Amer med Ass 143 329