Document 6BzRaXLMDYONa8LkYqgLkkB44

FILE NAME Kent KNT DATE 1951 Mar DOC KNT120 DOCUMENT DESCRIPTION Journal Article - Cancer of the Lung in Relation to Tobacco - British Journal of Cancer BRITISH JOURNAL OF CANCER VOL V MARCH 1951 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 Arsenic Content of Cigarettes In an earlier 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 g which is muunerically the same as parts per million The results given in this and the carlier 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 arsonic content 0.0 to 4-3 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 type in Western Europe to the arsenicpoor Turkish type in the East with an intermediate European zone which apcco3rds with Hutson's 1937 account of tobacco culture in Europe quoted below 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 lung Since arsenic is under 1-20 1-20 2 M. E. DAFF R. DOLL AND E. L. KENNAWAY TABLE Arsenic Content of Cigarettes Brands other than English Brand U.S.A. cigarettescigaret es As gper g Brand C . 2 . 46.4 46.7 " P.M. . 1 51.0 Canada Brand K 4 . " 0 . 5 " W 6 " B.C. . 8 . 36-8 58.2 47-1 55-1 - 8.7 18-4 8-6 18-7 9-1 . 411 46-5 57-9 79.5 67.5 41.7 . 43.5 57.6 42.5 Norway Brand B " T . - 71.7 65-8 74.6 . 4 . 54.4 52.4 55-6 49-7 Switzerland Brand P . 4 . 6.4 3.1 3.9 3.4 Italy Brand N Austria Brand D " M Poland Brand Z Bulgaria Brand A " R ' 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 2.1 12 2.7 1.5 : 4 . 0-7 ; 12 12 nil 0-3 . 4 0-6 0-6 nil 0.2 some circumstances carcinogenic in Neubauer 1947 ; Currie 1947 ] 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 exp to arsenic are given by the Chief Inspector of Factories 1939 In a cal < 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 56 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 CANCER OF THE LUNG IN RELATION TO TOBACCO 3 notified pulmonary carcinoma occurring in arsenical sheep workers have been 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 if 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 1) hee NTS anya it seems better to publish the available data now in the hope of promoting first- ETT apy hand inquiry in appropriate countries SINT So far as we know the only statistical studies of cancer of the lung in relation pues to cigarette smoking which have come from any countries other than Great Peret 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 B 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 a<s< 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 od Thus populations in eastern Europe which are subject to the first of these ae 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 : . 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 Tobacco consumption million lb. 1925 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 37.2+ 37.2+ . 17,820,950 : 2.09 1947 40.77 . 18.870,785 . 2-16 1949 39.77 . 20,900,009 . * Figures from Hutson 1937 Figures provided by the Turkish Embassy ++ 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 Culhane Tevfik Saglam . The Sect for Int Diseases of Gureba Tevfik Year . 1899-1908 1923-1926 Number of patients . 4270 . 2343 . Pulmonary tumour 2 + 7 Rate per thousand 46 47 2.1 3.0 Saglam : : . . . . 1931-32 . 1459 9 7:4 6.2 Haydarpaxa Numune Hast Tevfik Saglam . 1936-1939 . 4230 . 24 - 5.6 5 * 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 Gullane Reinhard . . . 1899-1908 . 800 . 3 . Gullane 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 . Rate per 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 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- monary carcinoma has increased in a great proportion seno Saglam rejects cigarette as a carcinoma Some authors believe that smoking tobacco and inhaling the smoke factor in the incidence of bronchial there exists a relationship between and pulmonary carcinoma Animal experiments seem to support this point of view Some authors are of the opinion 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 III Cases of Cancer of the Lung Among Autopsies Carried Out at the University of Istanbul 1935 1950 Number of autopsies Poriod All cases 1935-9 , 1940-4 1945-9 . 1949 5. 0 Male 1833 2585 2612 767 Female 947 747 1323 488 Total 2780 C. 3332 3935 . 1255 . All cancor Male 217 302 359 104 Female 97 70 129 53 Total 314 . 372 488 : 157 . Cancer of lung Mulo 33 48 73 31 Female 5 7 10 4 Total 38 55 83 35 Changes in incidence will be seen more clearly in Table IX where cases of cancer of the lung are shown as percentages of all autopsies 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 for tobacco man's Year 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 about Yugoslavia but Dr. of the population He writes that the kinds of the smoking habits 66 are : a type Makedonija cigarettes ; tobacco smoked in Yugoslavia b type c type Vojcodina pipe and cigars Hercegovina cigarettes and Makedonija Ljubljana 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 of type part Yugoslavia there are smoked cigars laansdt w pa ir pethe Use of tobacco for snuffing is quite insignificant . " Before 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 the numbers of autopsies and of those on all a statement of cases of malignant disease and of cancer of the lung by sex carried out at the Clinical Hospital Slovenia during 1925 to 1949. 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 Poriod 1925-9 1930-4 . 1935-9 . 1940-4 1945-9 , 1948-9 , All cases Malo Feinale Total 564 793 1063 1080 1929 897 553 765 868 1050 1589 791 1117 . 1558 1931 . 2130 : 3518 . 1688 Number of autopsies All cancer Male Female Total 72 117 132 129 246 141 65 91 113 135 292 154 137 . 208 : 246 264 . 538 . 295 . See footnote to Table III Cancer of lung Male 8 5 11 18 28 19 Fomale 2 I 1 1 9 ? Total 10 6 12 19 38 26 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^'raldes 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 Percentage of tobacco 1936 to 1949 YeYar ear Tobacco consumption lb. per head 1936 1937 1940 1943 1945 1947 1949 3.5 4.0 4.6 4.9 5.9 5.7 4.5 grown Imported from a . Balkans U.S.A. Other areas 6 . 10 . 38 . 46 12 Lee tes 12 , es tee 18 . +e . . . -- 20 , ees te ke 19 18 ii ii . : Lees 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 a 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 ) 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 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 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 M. E. DAFF R. DOLL AND E. L. KENNAWAY 500 , 500 Males 400 300 | 200- 100 Tobacco e. Females 1929 1931 1933 1935 1937 1939 1941 1943 1945 1947 1949 Fio Cancer of lung Deaths 1929-1949 Consumption of tobacco ( hundred thousand pounds 1936-1949 Switzerland official figures for the consumption of pipe tobacco and cigarettes cigaretes are misleading smoking is most common in rural areas TABLE Consumption of Various Types of Tobacco in Norway Kreyberg 1931 to 1947 Year . 1931 1932 1936 1937 1940 1943 1946 1947 Tobacco consumption lb. per head 1.4 1.4 : : 1.7 . : 1.9 . . 2.2 : 1.0 - 2-6 2.9 - Percentage of tobacco in form of: Cigars 2 3 3 3 3 1 I 1 Cigarettes . 36 . 35 . : 36 . 39 . 39 : - 49 : 41 : 44 : Pipe tobacco 62 62 61 58 58 49 58 55 2 Prof. Leiv Kreyberg has supplied figures for the deaths attributed to cancer of the lung by sex for the years years 1930 to 1948 Fig 2 3 for deaths sepa- CANCER OF THE LUNG IN RELATION TO TOBACCO 9 in urban and rural areas and for the population by sex The calculated rately from cancer of the lung are shown in Table X. Jakobsen death rates according to Mr. Jakobsen The national figures are reasonably reliable as his last illness is required to < The doctor who has treated the deceased during which must be fill in an official certificate stating the cause of death . . . stated in medical terms as precisely precisely as possible and it is not permitted to use such as " disease of the heart or " disease of the lungs general diagnoses The 160- Deaths Cancer Cancer of lung / 120- 120- 80F * e @. sv / 401- ow!/ o/ m / ^' -e-9-9-0-0 8" Tobacco Tobacco y ' : 2-8, , : y LA i e. @ oy Ne: 1934 1930 1932 1934 1936 1935 1940 1942 1944 1948 1946 1948 FIG Cancer of lung Deaths Consumption_of_tobacco Consumption_of_tobaco Consumption_of_tobacco hundred metric tons Norway 1930-1947 Kroyberg 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 Urban Rural 1930-38 1939-47 Male Female Persons 24 : 19 . 21 . 63 : 42 : 52 ' Male 14 30 Female . 12 24 Persona 13 27 30 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- 1930-38 1939-47 urban : rural " ratio male 1-7 ; female 1.6 1 + male 2.1 1 female 8 1 c The increase between 1930 and 1947 has been greater in the towns than in the country and greater for men than for women Urban increase male 2.6 1 ; female 2 1 Rural " male 2.1 ; female 2-0 1 [ Males ato ti tite ety dy 1930 1932 1934 1936 1935 1940 1942 1944 1946 1948 FIG 3. Cancer of lung Deaths Norway 1930-1947 Kreyberg Kreyberg Sweden Snuff used for chewing and for insufflation makesmakes up a very large but diminish- ing proportion of all the tobacco products consumed Hutson 1937 Prof. Berven personal communication Table VII Prof. Berven " Elis fine powder like the English snuff and is inhaled in writes Snuff is a very the nose For chewing there are two small quantities through pinches i.e. about types a The same type of snuff 3 b4ig the lip and the one teaspoonful mandible taken from the snuff is put in between and is chewed backwards and forwards until it becomes a tough mass in size of about a hazel which is lying at the same place about hours . . . 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 Year Cigars and cigar Cigarettes Tobacco for Tobacco for Snuff Tobacco Consumption lb. per head headhead per year 7 rettes smoking chewing Snuff Tobacco . % % % % % % . 1908 . 10.8 3.3 4.4 : 1921 10.1 8.3 11.1 * 1931 9.3 16.1 13.0 . 1936 8.5 22.3 15.5 e 1944 6.7 27.9 23.7 t 1948 5.1 44.9 16.3 : 1949 4.7 46.9 15.6 7.9 3.6 1.8 1.2 0.6 0.4 0.4 73.6 66.9 59.8 52.5 41 33.3 32.4 26.4 33.1 40.2 47.5 58.9 66.7 07.6 2.08 2.23 1.73 1.55 1.15 1.06 1.02 0.7 1.1 1.2 1.4 1.7 2.1 2.1 from which they bite 1 to cm This piece is chewed to a firm 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 consumption particularly Smoking habits in Iceland are discussed by Dungal 1950 according to whom The of tobacco inin the form of cigarettes has certainly been much less in Iceland than in most European countries and America Dungal's figures for cigarette consumption and for the incidence of lung car- cinoma are summarized in Table IX Britain Data with regard to tobacco consumption and the incidence of cancer of the lungin Britain have been presented previously Kennaway and Kennaway 1947 ; Fig 4 5 New data on the autopsy incidence of cancer of the lungin British hospitals have been collected Table VIII TABLE VIII --Cases of Cancer of the Lung Among Autopsies Performed at Three British Hospitals 1925-48 Hospital Period Glasgow Western . Infirmary Cappell St. Mary's London . Newcomb 1925-9 . 1930-4 1935-9 1940-4 1945-8 . 1947-8 1930-4 1935 9 . All cases M. F. Total Numberof autopsies All cancers Cancer of the lung .. F. Total M. F. Total oe ae oe . . an 827 746 -. -. - . - 481 442 1154 . 133 1214 . 153 1395 . 190 1273 180 1324 . 220 687 103 1308 . 140 1188 . 171 83 82 124 124 133 68 86F2 112 216 235 314 304 353 171 77217 283 . 287886 12 # . 287886 606554al 6762204 . 287886 6065 4al 6762204 . 287886 606554al 6762204 . 287886 606554al 6762204 287886 . 287886 6065 4al 6762204 . 287886 606554al 6762204 1945-8 683 428 HIIl . 139 2987 229 . 1947-8 . 371 229 600 83 2987 130 1 St. Bartholomew's . 1930-4 . 1056 558 1614 . 206 2987 301 . London 1935-9 . 987 528 1515 . 192 121 313 . Cunningham 1940-4 1945-8 1947-8 544 301 ve 217 125 es . 761 426 : ae 111 82 171 2. 60 82 87 . * See also Table IX 7255 88ax 3885 7255 3885 7255 88ax 3885 7255 88ax 3885 : 73 39 73 A8 39 12 M. E. DAFF R. DOLL AND E. L. KENNAWAY 10000- Males 8000 6000- 4000- ToTobbacco acco _ Tobacco Po ced . : : 2000- ee Females Pa en 1948 Hi 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 : F thousand pounds United Kingdom 1924 1949 g} l - * t x 5 \ e. ey , o-? / - ~N a * \ a fv Nf Ne a - _ Nee ee x / x 2H aN RI \ 25 27 29 30 35 32 i 38 ji 1 it s 1924 25 26 27 28 29 30 32 34 36 37 38 39 40 41 42 43 44 45 46 47 48 49 a FIG 5.Consumption of tobacco lb. per head United Kingdom Switzerland and Norway ie o .@... Un.i@ted Kingdom @---@---0 Switzerland XX XX ^ 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 Switzerland and Iceland are presented together The cases of lung Ycaungcoesrlaavrie ashown 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 : a 1 A high proportion of autopsies on cases of cancer between 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 is unlike 2 The experience concerning males in Istanbul in recent years not 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 however indicate a higher incidence Table X and too Swiss national statistics 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 Wales Switzerland and Norway for selected years between 1931 and 1947 and estimates of the annual rates of consumption of tobacco 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 All 20-3040 50 60 70- Males England and Wules 1947 48.4 7.4 7.8 7.1 5.3 4.0 2-6 Norway 1946 49.3 8.6 7.9 6.6 5.0 3.3 2.7 Population Per cent of all ages Females Females Switzerland 1950 48.3 7.4 7.2 7.1 5.3 3.7 2.4 . All . 20- 3040-50. 60 _ . 70- 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 interinediate 9-0 these small differences cannot account for the differences in the death and justify the use of crude death ~ rates] ri = 3 4 y fyon PI 5Hewl 4a A : .4 refa&zxaa> juawfig uondmsuc )TSt-1L6Z0-06180-9061 ec-zerTE-621Oe-EG Le-oReT LE-OFET )er SP-LP6T (9-0(1-0(6-0(ra(3 (6-3 {ep (1-6 I ) oe (peoy 818) 8935) 8989) jes oot ) ) jenury ur 6-1 0-3 6-8 aod a 6-8 OO om - . - - . se - i a - 0-0OeI ( - $F - (8130) LT 13 BS 8 ) 61 a) isdomny osanqay LEGT ZbGLTPOT OS6t eT6t ee1) 6E6T J - * ' * . * . . . . . . . * * * . , ' ' * be: . . * yw LZ Lung cent as Per cent Diagnosed at Different on cent of All All Autopsies Autopsies Autopsies Autopsies and and of All All Cancer CaCannccererDiagnosed Diagnosed Diagnosed Diagnosed atAutopsyAutopsy Autopsy Diferent Diferent 8-2 88 22 8-8 .Cancer Countries? JO Countries _ aguea OpRUIE qed a - G+ $1 1-9 9g autopsies Cancer Cancer Cancer . the lung lung ee per cent of : cancer rs td 6-0 L-0 tobaco Anual consumption od 8-F GL oP Locality Locality Jed [Ty 1894-198 1894-198 hospitals 1894-198 hospitals * a Male Male Female Female Female . 0.96 1.6 0.96 1.6 Li3 os Male 0.961.6 26 Femalo Femalo 190 02 fer: and Holmes 1924-1928 1924-1928 : * . * 2.11 2.11 0 . oe Femalo Persons Persons . OFT 19002 cgts ) Lip 86s . . * 1911 13 ( a * 7 General 943 Infirmary Infirmay 189-132 PCIOGWLZU Capel 8 <- 189-132 1-18-90 12--78 193-1937 193-1937 1f-% 6% o-1^'eF rg Le 2.31 2.31 FP g-F Te oe 16.5 14.5 14.5 1% 11.32 11.32 11.32 6-0 Vt 1934 36 ( 2-7 8-F 8-9 8:3 Gi OF amie GlasgowCap el sordgnetcad1935-39 1940-4 1940-4 a - _ - - 7 OT 4.4 oe 6-1 -%6-1 2.8 22.8 12.9 12.9 12.9 18.818.81-0 1-0 9-0 a * 2 . 9-3 Z- 8-0 6-0 Layar yy [Ty 1945-48 LondonMary's Newcomb Bartholmew's Bartholomew's 1935-39 1935-39 a * 4.8 4.8 a a 2.0 - .. 21.1 1935-39 98 3.8 69 oS Le 21.1 13.7 8.0 8.0 18.9 18.9 OT LT GT BO bP 1S " " ~ * " * * * * - 8 7 27.7 27.7 . 13.7 * 23.3 23.3 * * " 8 * * * Saglam BE-OS* 1940-41940-41940-4 S86I-Y8T3.7 Cuningham Cuningham Cuningham *poneg 1935-39 3.7 P8-086T 68-HS6T 4.6 4.6 PROk6T 7.0 7.0 &P-EFG1 GR 19.3 Se6T 38.7 38.7 16.7GE 16.7 16.7 31.0 31.0 31.0 BR-OFET 6p-SPET 1-Le6r Sb-S6T $P-LPGI SBLFET SP-LESI oc-eRET 6P-8FET BET * 1937 * * Schwartz 1945-49 yAremiygu 2.8 * 17.0 s, Ljublan MOUL[TIABE 1.1 xX] Kosir 1925-291930-34 Jersue1y .00.61.0 wopuoc7 0.s 6 arepseg) uvqity) 0.7 * * * , : 1947 S (Aanquefyg) *{eBumq) Adeuay yeqidsoy 6 M@UIOj T . * . 1936 m1ADISOHRX Meynburg 1945-49 1945-49 UIDRNLG1927-41 spec] 1.5 dre1.1 4g uOpuoy Ay 1 -8paquesy p1anpsohvnu. ltqnl] 1936 3.5Haclydoy UDNAATuszoyyseAargeqey g9g KENAWYKENAWY suliqnt{y x YearYearCancer Cancer Cancer the . Annual Cancer the Annual (0 57 (0 3-2 egts egts 2 *** Persons 14293 FL100100 )OL 3.8("2.8 JSeT7.49642 Am.40 1940 162 gp 321222 115 AT ~ 366 * 131 * * ST orf 206 5.4 cgts cgts 4 2189 398 39822189 106 17 Jo 183 * 6 USh a OF 0% 0% SI FS 98 OF the figures United habits Thesmoking difernt TUNG Ireland cent habits population population diference diference diference Northern importanceimportance importance poulation this S29 _ PUNLOZ ( LP6T AL war - no * 40 ur (FE {-2 Ul fo eauryau0eqoy and (SP6T){Sets prey t;oE OF 6E61 oF 6F 6-England England and Gg Od 43.0501 Scotland avil*a(pbvolyse-g) WalesWalesWales 8739) Northern Ireland Kingdom opr . punpbury "uondmsuon KingdomKingdom uorTIur qonuef) United pusfazqiMg ue dUN] SURsuie "oF "OF &g gg Tk 9F6or 90L Kingdom ys bueary ovaDngo,s ayy Ynin {0 sa0ung pasoduoy wot + saypar aSayfe pues YOO oY} Jed JO se7ea ft+4 LT 61 1% 61 Jaonezy . A 89 $8 Tw YdeGY 9 te ee 98 PE aead LLT Sst ae * " (9-B's80) AaBqo4yyeuny *(peoy/ )op roe (egHE(8S(8 (ee twato) * rs4 a ge Veebee pe op:+ - * > > Sunyuoru SHOSIsOarTeya fe ag Tg gor ter ergtag gz TY purSugy eyy Jed ys Jo a lg 6 eP ap $s 69 14 L . seqez Touey xone Sg 86 Gel I9T mrs, yecT * ' ZS Wes 998 86E | ULOpZui A104 yy you eourysdupay cau 142) PUBEITOY} ou 04 jo st ODAeBzqOa}rpMeuysIONGouslyip ucendapoqangsy orqutiean JOT sryy pUE}OgUI "ana eqnea Aq somaysytqey ayy je ory, Furpoursques gout . SejeA, pues PURJaAyT wopSuny puvlsugypurejqoagWlsy_ION peyruy * J f - TOs oTS61 GEGT (OS6T L^'6T OPGI Spel 9FGEI (LEGIT oyy aed 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 England and Wales M. 100 170 F. 100 137 Persons 100 162 1936-7 as porcentage of 1931 2 - Switzerland M. F. Persons . 100 100 100 . . 141 111 132 : M. 100 177 100 252 100 173 1946-7 as porcontage of 1936 7 100 100 100 100 : 227 . 200 175 196 : 100 215 NorwayNorway 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 from cancer of the Jung ~ 1931 1947 death 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 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 . . . . 71 England and Wales . . % 4 Switzerland . . . . 19 Z The ratios of cancer of the lung in women to total autopsies in women also 2 indicates a relatively low incidence in women in Turkey and Yugoslavia Table IX CANCER OF THE LUNG IN RELATION TO TOBACCO 17 The relation between increases in the consumption of tobacco and in cancer of the lung 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 shown by 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 a7nd 1946-7 TABLE Comparison between Tobacco Consumption Cigarette Consumption and Death Rate Persons from Cancer of the Lung at Different Periods Country 1946 Tobacco consumption lb. per head Cigarette consumption lb. per head a7s percentage of 1936 7 England and Wales . 128 . 145 Switzerland . . . 155 . 170 Norway . . . 153 . 185 Death rate from cancer of the lung 227 196 202 England and Wales Norway . 1936-7 as porcentage of 1931 2 - . . 120 . 123 . . 129 . 130 * 1949 as percentage of 1939 X 162 187 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 XII 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 Tobucco consumption lb. por head Cigarette consumption lb. per head Death rate from cancer of the lung England and Wales as percentage of Norway . 1946-7 : : . . 180 . 350 499 1936-7 . . . . 190 . 446 444 1931-2 . . . . 232 470 513 England and Wales as percentage of Switzerland 1946-7 . . . . 085 : 162 205 1949 1936-7 . : : . 104 . 266 1939 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 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- sumption This is because a much smaller proportion of the tobacco is consumed in the form of cigarettes in Switzerland than in England Clearly no exact proportionality has been found in the data so far available 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 association 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 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 population of any East European country The official figures for the consumption of grown tobacco are liable to the error that a portion may escape record 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 benzpyrene 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 carcinogenic importance of tobacco sinoke 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 possibilitics 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 cigar- ette 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 In Yugoslavia Turkey Greece and Bulgaria the tobacco consumed is almost wholly grown of Turkish type and in the form of ecigarettes 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 U.S.A. and 9 per cent the lung upon the two 1:07 it is greater in in men than in women about 85 per cent of the tobacco consumed from the from the Balkan countries The incidence of canceorf sexes is not very different death rate male to female urban than in rural districts and this difference is greater 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 Norway 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 cigarettes lung are therefore quite different in extent from those in the of tobacco ; quantity consumed they are more like though still different from thosein the quantity of 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 Hribar of Istanbul and Prof. 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 Kantonspital the Prof. H. R. Schinz of the Z^...richProf. H. v Meyenburg of Pathological Institute Z^...rich Mr. S. T. Hisim of the Turkish Embassy Mr. Legation Popov of the Bulgarian Prof. Elis Berven of Stockholm Prof. H. E. Rawlinson of the University of Alberta the Burcau F^'d^'ralde Statistique Berne and the Direction G^'n^'radles Douanes Berne for their kindnessin supply- ing us with statistical and other material In this countrycountry 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 CancerCampaign and the Anna Fuller Fund for generous grants REFERENCES BRADFORD A. and FANING E. 1948 Brit J. indust Med 5. 2 Chief Inspector of FactoriesFactories and Workshops Ann Rep p 22. London H.M. Stationery Office 1943 Ibid p 45 Bull CURRIE A. 1947 Brit med 4 402 Daff M. E. aND KENNAWAY E. 1950 Brit J. Cancer 4 173 DOLL R. AND BRADFORD 1950 Brit med J. ii 739 DUNGAL 1950 Lancet ii 245 HEADY J. A. AND E. 1949 Brit J. KENNAWAY Cancer HENRY S. 1950 Ann Roy Coll Sury England 7 425 Bulletin Hutson J. 1937 U.S. Dept. of Agric Technical 3 311 No. 587 KENNAWAY E. L. AND KENNAWAY N. 1947 Brit J. Cancer 1 260 MONTGOMERY H. AND WAISMAN M 1941 J. Invest Derm 4 365 NEUBAUER . 1947 Brit J. Cancer 1 192 SAGLAM 1944 Bull Fac Med Istanbul Haziran 1944 p 3793 Yil 7 Sayi 2 Imumi No. 28 Nisan- SEMON H. 1945 Proc Roy Soc Med 38 Section of Dermatology 128 Stocks Cancer 1936 Ann Rep Brit Emp Camp 13 19476 Studies on Regional Population Medical and Cancer Death Rates Subjects No. 1. and Local Differences in London H.M. Stationery Office WYNDER E. AND GRAHAM E. 1950 J. Amer med Ass 143 329