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THE JOURNAL OF THE AMERIiCAN'MEDIICAL ASSOCIATION September 28, 1970 Vol 2113, No 13 Recent Trends Ernest L. Wynder, 11~ID; Kiyohiko Z?'abuchv, TVID; and Edward' J. Beattie, Jr., MD A retrospective epidemiologic investigat'io'n o f' 350 lung cancer patients confirmed the close association between . cigarette smoking and lung cancer, particularly o f the squamous and'oat cell types. New trends in this study ' kl. _% _' show that there is a decrease in relative risk f or those - patients developing' lung' cancer ten years a fter they have switched to filter cigarettes, possibly due to the lower "tar'''content in filter cigarettes smoked by these patients. ;~YS The risk also declines a f ter cornplete' cessation o f smoking d thh llfh an appearso approac teevie o nonarr~o'ers a4ter 'k` 13 years of not smoking. ~'ucrther efforts to produce less .number of cigarettes smoked per day. If''•tar" is the principal harmful ut- gredient4 then it would be sufficient to reduce the concentration of' the tar. The Hammond study on ex- smokers aged S0 to 69 years who had smoked 20 or more cigarettes daily, shows that after ten years of nott smoking they have a death rate sim- flar to that of nonsmokers.' These two pieces of evidence taken y•'z together suggest the following hy- ' harm f'ul tobacco products should be continued and expand ed although no smoking or cessation o f smoking is the most effective prevention against lung cancer. W ith a wealth of' epidemio- ibgic' studies on the etiol- ogy of' lung cancer in the literature,,it may not seem worth the effort to report yet' again on the en- vironmental background of a group of lung cancer patientg.'1 ' However, such a study is of value if it cart show evidence of changes, particularl{y in time trends, in the epidemiological background of these patients. From the Division of Environmental Cancerigenesia, SSoan-Kettering, Inatitute for Cancer Research. and' the Division of Epidemiology, American 13ealth~ Fbaada- tioa (Dts Wynder and Mabucbi) and,the JY1MlA. Sept 28. 1970 e Vol 223, Mo 13 Ih a great many epidemioiogic studies, it has been found that, among cigarette smokers, the risk of lung cancer increases with the num- ber of cigarettes smoked per day.'" In other words, there is a dose-re- sponse relationship. This suggests that reducing dosage by means of reducing the concentration of the smoke from each cigarette might have the same effect as reducing, the Department of Surgery, \'demorial'Hoapital for Cancer & Allied Diseases, New York (Dr. Beattie). Reprint requests to 2 E End Ave. New York 10021' (Dr. Wynder). pothesis s If tar is the principal lung-cancer in- ducing faetarr then people who have switched from high tar cigarettesi to low' tar cigarettes should have lower rates of lung cancer t'han those who , continue to smoke high tar eigarettes- ~ this taking place tien or'more years a'f> ter the switch. The present study was undertaken to test this hypothesis. Methods of' Study Lun!g, cancer patients admitted to the ,1~lemorial Sloan-Kettering Can- cer Center in New York City are interviewed routinely about their background and social habits. Each patient included in this re- port has a histologically-proven lung cancer andl was interviewed between November 19% and August 1'969. The study group consisted of 210 men and 30 women with Kreyberg Lung Cancer-Wynder et al' 22211 -A• .. 11 .

Table 1.-Type of'Smoking and!Number of Cigarettes Smoked by Lung Cancer Patients and•Contral's. Totatt. . IVO. - (1/.)~. Pla~ (Y.). 210' (73.9): 30 (45.5) 7:00:1, 74 (26.U/ 36' (54.5) 2.06:1 234 (100) 66 (100W ' . 4J0:1 group' 1 cancer of the lung (squa- that subclass and let m, and m, stand rnous and oat cell types), and 74 men for the number of nonsmoking cases arld 36 women with Kreyberg, group and' controls. Then the relative risk 2(glandular)' cancer of the lung. The control group interviewedl at Mlemorial~at the same time was twice f+art'he subclass= the size of the cancer group and tnat ehed' by sex and age to the male n, nr m, m.. Kreyberg 1 patients and all female Thus, for those smoking 41 or more cancer patients. The criterion for in- filtered cigarettes per day, n,=25, dzwidua'I's in the control group was n_-7; firom Ta'ble 1, mt-3; rn.-$8t that t'hey' should have no known to- and thezel.ative risk is 104'.8: bacco-related diseases," Tht: risk for any subclass relative: Results to that for nonsmokers was computed Sex Ratio and Hrstofogy:-When in a standard fashion,° as follows: the sex ratio of patients with the Let n, and n} stand for the number different histological types of cancer ,\ J of cases and controls respectively in was examined, the'Kreyberg,11 group >aa1. K'r.yberg 1 Kreyb.rg•'2 - '` Control -" r e ~ ' Nonsmokers 3 (1.4) N o. 6I ( (8.1) No~ 88 ( /,) (21.0) Current smokera •L exemokers (I•9 yr) C7g#rette smokers' 191 (91.0) 61' (82.4) 199 (47.4)' Pipes and/or cigars only 10 (4.8)' 3 (4:1): 64 (1'5.2) Essmokers (1'0 + yr) Cigarettes 6 (2.9) 3 (4.1) 65 (16:5) Pipes and/or cigars only 0 (0) 1 (1•4q 4 (1.0). Total Mal. Patients • 230 (100) 74 (100) 420 (I00)'. No. of cigarettes por day 1to9 7 (3.6) 1 (1.6), 42 . (15.9) 10 to 20 ~ 57 (28.9) 20 (31.3)', 114 (43.2) 21'1 to. 40 ~ . 74 (37.6) 34, (53.1')' 82 (31.1) 4t,- 59 (29.9) 9 (14.01 26 (9.8) Tota( C)garett..5moken 197 (100) 6x (100) 264' (100) Femate Nonsmokers 5 (167)i is (41.73 76 , W•6) Current smokers + eIISmOkers (1•9'yr) CigareRe serokers 24 (80.0) 21 (58.3) 53 (40.2) Easmokers (10~+ yr) 1 (3.3) 0 (0) 3 (2:3) Total Fetnaa Patients 30 (100) 36' (100) 132 (100) No. o! oiganttas per day, 1'to 9 11 (4,0) 2 (9:51 19 (33.91 10 to 20 13: (52.01 11' (52:4) 24 (K¢19) . 21,to 40 g' (32•0) 7 (33.3). 10 (17:9),, 41+ 3 (12.0) 1 (4.8)' 3 15A) ~ Total Cfgsrett. Smokers' 25 (100) 21 (1!00) 56 (1i00) Table 2:-Histologacal Type and Sex' Ratio oflung,Cancer Patients AAali ~ Ftmate 5e. Ratio I W F. ' (I a Y: matd K'reybird group. 1'K'r.yberg, group 2 had a greater predominance of men than, the Kreyberg 2 group (Table 2). Age Diatribcction.-Niale Kreyberg 1 cancer patients were somewhat' older than the male Kreyberg 2 pa- tients a'nd' both groups of wotnen,, though the •dif{erence between thee male Kreyberg 1' and Kreyberg 2 groups was ~ not ~ sig'nifirant (t'-1.19, 0.15'>P>0AD)'.(Tab~le 3).ReligirJn.-T.he male Kreyberg 1. cancer group included a significantly lower percentage of Jews than' both Kreyberg 2 cancer (,1'-3.6a; dii-1, 10>P>0.105) and control groups (t' =25.65; df-1, 0.005>P) (Table 4). The female Kreyberg 2 cancer group also contained'a lower propor- tion of Jews than the eontrols, but the difference was not statistically significant. Smok'ing,-Ainong the' men in thee study there was a signnficanttyg'reat- er percentage of smokers in both his- tolog'icalF groups than in the'controls; and greater in Kreyberg 1 than in Kreyberg 2' (Table 1). (kGeyberg 1 and control: X'-41.61, df=1. 0.005 >'P; Kreyberg 2 and control: X'= 5.93, df-_ 1, 0.05>P>0.10; Kreyberg 1 and Kreyberg 2: Y'-5:93; d'f =1, 0.05>P>0:01). The female Krey- berg1 group also: contained! a, sig- nificantly higher percentage of ciga- rette smokers than the controls'(X"_ 14!77; df~-1, 0:05>P). Tlie' differ- ence in srnokers, between the female Kreyberg 2 and control group was' not statistically significant W_ 223idf,'1', 0.25>P>0.1~0). Arrtount an'd Type ot Cigarette Smoked..-Data on amount smoked refers to the number of' cigarettes smoked daily during the Iest five years of'smoking. Any patient who had' smoked at least one cigarette a day for 20 years or more was defined as a cigarette smoker and, was in- cluded in this analysis. If, a patient smoked for less than 20 years, a dailyy number of' cigarettes' smoked was ca'lculated as follows: (daily number of ci garettes )_( the average number of cigarettes per day for past &years) 2222 JAMA. Sept 28, 1970, • Yo( 213, No 13 Lung Cancer-Wynder at at

1 r Table 3.-Age Distribution of Lung Cancer Patients Maie Female Kreyberg 2 Krsyberg li Kreyberg 2 ~- I No. (y.) No. No. 6 (8.1) 1 (3.3) i 4 (11.1) 7 (9.5) 4 (13.3)1 2 (5.6) 23 (31.1) 14 (46:7)' _ 1s (41.7) 32 (43.2) 9 (30AT 12 (30.6) 6 (8.1) 2' (6:7): 4 (12'.111 0 (0) 0 MY „ 0 (0) 74 (100) 30 (1o0), 36 (loo) , 67.8 56J6 56.7 Age at Kteyberg,l DiaRnosit (YN No. (!%.Y 30-39 31 (1.4) 4049 31 (14!8) 50-59 56' (26.7) 60-69 63! (39.5) 70-79 331 (15.7) :. ac+ 4' (1.91 Totaii 210 (100) M.aa Age 60:2' Religion Male Table 4.-Religious Distribution of Lung Cancer Patients and Controls. Jews CathoNbs Protestants Totals F.ma(e . Jews ''Tathoiics Protestants Totals Kreyb•rg,1 Kreyberg 2 Control' Ne (•!•) No. (9•) i Na (Y•)' 29 (13.8) Ii6 (24.3) 139 (33.A 116 (55.2) 33 (44.6) 18+t (43.8) 65 (31.0) 23 (31.1) 97 (23.1) 210 (100) 74 (100), 420 1100) S (L6.7) 14 (3&9)', 38 (28.8) 1!S (50.0) 13 (36J1') 56 (42.4) 10 (33.3) 9 (254) 38 C18.81 30 (100) 36, (100) 132 (100) Table 5: Numberand'.Ty,pe of Cigarettes Smoked by Ma1e Lung,Cancer Patients andiCo'ntrols Regular No. ' - Krsyberg 1 Control Cigarettes i p.r oay I to 9 4 (4.9) 6' (9.7) ~ 6 3150 10 to 20, 24 (t9.) (:0) 21 to 40i 30 (37.0) 21 (33:9) 41 + 23 C18.4) 4 (6.5) Totals 191 (1''00), 62 ' (100). Filt.r' Kreyb.rg 1 Controi No. (•/.) No. (y.). 2 (3.0) 11 17 (25.8) 36'. 22 (33.3) 28 25 (37.9) 7' 66 (100) 82 (13.3) (43,9) . (34.1) (81S). (100) •P.rsans who smoked'. Nlt.rs for ten or more years aft.r switching from r.guiar cigantt.s. Table 6.-Duration,of'Exsmoking in Ma(e Lung Cancer Patients and Controls. Knyberg.1 Kr.yberg2. No. Y.ars Since ~---~ Stopping 5moking, Na (*/.) Nb. (°/,), 11 to 3 18 (50i0) 3 (25:0) 4 to 6l g (22:2) 3(25:0) 7 to 12 g (22.2) 3 (25.0) 13 + 2 (5.6) 3 (25.0) Totals 36 (100) 12 (100) x (years of snnokingJ20 years). T"hus, a patient smokin'g, 20 ciga-, rettes, daalyfor'tew years! was classi-fi'ed as' a ten-per-day cigarettee smoker. However,, such ad'p'ustments' were rarely necessary. Aalnng, cigarette smokers there was' a significantly greater percent- age of inen.who smoked' in excess of JAMA. Sept 28, 1970 • Vol 213, No 13 .r~. Controi I No. (Y•)i 22 (1'7.6) 17 (13.6). 31, (24.81 55 I (44.0) 125' (100) two ~ packs of cigarettes a day in the. Kreyberg 1 group than inboth Krey- berg 2 and control groups, (Krey- berg 1 and, 2: (X'=5.a3, df=1,, 0:0'5>P>0:0b; Kreyberg 1 and con- trol: X"=29.00, df _ 1I, 0:005>P) (Table 1). A similar, but not sta- tistically sigpificant, trend was noted, for men between the Kreyberg 2 group, and controls, and' for women between I+Creyberg, 2 group and con- trols. For the purpose of testing the hy- pothesis presented in the beginning of this communication, the reiative risk for' Kreyberg 1 lung cancer was cal+culated,by the method stated, be- fore for nonfilter (regular) vs filter. .. cigarette smokers. The former group included persons who smoked non- filter cigarett'es on1y. The latter, onn the other hand, comprised individ- uals'who changed'to filter cigarettes and had smoked! them for at least ten years. In the preliminary analy- sis, it was found that persons who had quit smoking for a long periodof' time had smoked more non'fiSter' cigarettes before stbppin'g than either current or recent exsmokers; as'.. might be expected because there. were, of course, fewer filter cigarettes on the market ten, years ago than, today. In~addition, the con'troli group contained a sigtdificantly larger per- centage of' exsmokers of long dinra- tion (Table 11). Therefore„ for a sta- tistical comparison of'non'ftdter andfilter cigarettes, an arbitrary ten- year period of e)csmoking was chosen and anyone who had not smoked for at least ten years was excluded from, th'is,pa'rticular analysis. The results showed that the rela- tive risk increased in proportion to the greater number of eigarettes ~ smoked for both long-term filter and ~ nonfllter smokers, and that the lower' Q. relative risk noted for filter'srnokers Q. . as a whole (Fig 1) was' similar for all subclasses of smoking, atalmurlts' Q (Fig 2). The ratio of nonfiiter to ~ filter cigarette smokers was 1.22:1 for the Kreyberg 1 and 0:76:1i for the (~ control pa'tients, indicating more ~ nonfilter cigarette smokers inthe. Q liing, cancer' group than the contro'1, group (:Y'-3.76, df=1, 0:10>P> 0.05), (Table 5). Ttie, data also showed' a greater percentage of 40 ' plus-per-day filter cigarette smokers' in, the lung cancer group (37.9%)compared with nonfilter cigarette smokers (28.4%), a trend not as

~~ Current smokera & L.J ex-smacers II-9yrsJ' Q u-smokers t UD+yrs./ Case N' Control 6' 3' 6v g$ • (10+veirs) niaes L10+yearsl 1. Lung cancer risk by type of smoking, in men, Kreyberg groap1. . 1100 Filter cigarettes (10+yrs.) Nonsmoker risk • I Case N '' ConQrol' 10 - 20 21- 40 41 or more Cigarettes per Day 2. Lung cancer risk by number of cigarettes smoked, daiiy, in men, Kreyberg,group 1. 2 3 55 88 r~--Nonsmoker 4-6 l-1x 13• Years ol,Ex+smoking, 22241 JJ4'N1k1. SePt 28, 1970' • Vol 213. No 1T 1=-----r"'..~---- -~---Nonsmoker Ri!gular Filter Cigars ~-smater cigarettns cigarettes andlor, 3. LrYng cancer risk by years of exsrneking, in men, Kreyberg group 1.. Lung Cancer-VNynder et at r. ~a ~... . x,.

:f. -. apparent im the control group. . The data were examined in rela- tion to religion (Jewish and non- . Jewish), but only 22 of the patientss were Jewish men and this was too few toi a'ttempt an analysis in rela- tion to the type of 'cigarettes smoked. However,, removing Jews, from the .:, data 'showed~ . the relative risk to ~ be 462 2 for nonfilter smokers (74 cases, 5I0~controls) andl 26.8'for filter smok- ers (51 cases, 59~ controls), thus showing similar differences as found for the total group: Although the original matching of study to control cases was made by age, the data were eacamined by age group because when it was broken down by stnok- ing category it was possible ~ that the age distribution might be unbal- anced: While a: higher relative risk was consistently noted for regular, or nonfilter, cigarette smokers, in both the under 59 and over 60~age groups; the greatest difference in the relative risk for nonfilter and fil- ter smokers tended to be seen in the younger age group. A meaningful comparison of the groups smoking filter cigarettes for fe ..-: less than ten years by: amount smoked is not possible because onNy ` 23 patients with Kreyberg 1 lung cancer had smoked filter cigarettes~ for one to four years, and 21 for fiive to nine years. Cigar and Pipe Smokers.-Al- t'hough cigarette smoking was shown to be closely related to lung cancer, it must' be rernembered'i that cigar and pipe smokers also have a higher relative risk for lung cancer than nonsmokers (Fig 1) . Among pa- tients who smokedi cigars or pipes or both, in this stud{y, the amount con- sumed by the male Kreyberg 1 can- cer patients was greater than by the controls. Of seven Kreyberg 1 ran- cer patients who smoked cigars only, three smoked ten or more per day ; compared with four of 55 in the con- trofs: Among those who smoked pipes only, two of four cancer pa- tients and ten of 35~controls smokecl teni or more pipes daily. One can- JAMA, Sept 28, 1'970 9 Vol 213. NO 13 . 1958 '59, '60 '61 '65' '66 '67 '68 '69 Year of Report 4. Filter and nonfiYter "tar" yiields in the United States, 19Si9=1969. These data~are compiled reports in Consumer's, Report, Reader's Digest', Federali'1`rade Commission Reports, Wooten Reports, and Maxwell Report's. The results have been converted to correspond'to the standards employed by the Federal Trade Comrniission."° cer patient and' 26 control§ smoked both cigars and pipes. Of three Kreyberg 2 male cancer patients, one smoke& seven cigars daily, another 5 pipes daily, and the third smoked ten cigars and U pipes per day. Essmokers.-An examination of the men who had given up smoking at' least one year before hospital ad- mission showed that the lung cancer patients stopped smoking more re- eently tharn the controls (Table 6). The F{Creyberg 1 male group includedd a significantly higher percentage of' persons who stopped smoking less than, three years prior to diagnosis than the controls (1°-22:32, df=1, 0!Op5 >P ) ~. Thoughthe data seem to be based on a rather small number-of cases, ,the relative risk for Kreyberg I lung cancer was found to declane steadily after cessation of t'he smoking habit (Fig, 3'). The relative risk for those who stopped smoking up to three years previously was the same as for current smokers, but after 13 yearss the risk appearedl to be nearly the. same level as that of nonsmokers. Further analyses of exsmokers by age and different exposure to tobae-,

, co could not'be carried out because of' the paucity of'cases after such cross- tabulation. A review of the environmental his- tory of lung cancer patients who were Iong-tercn exsmokers might be f of' interest in view of determiningg probable exogenous factors that might be related to t'he etiology of' the cancer. The study contained; six lung cancer patients who had given up smoking at least ten years prior to diagnosis. Of'these six cases,,t'he only one to have smoked for Iless than 22 years had, a most unusual, epiderniolbgical history which, sug- gested his lung cancer could have been related to factors other than smoking. Between t'he ages of eight and ten years, the patient was treatedd for psoriasis with potassiumiarseniie. At' 27 years of' age, he had a lymph node tumor removed from his groin and received x-ray therapy. At the age of 37' years the patient hadi an epidermoid carcinoma of the scrot- urn as well as a squarnous cancer of the buttock. The present cancer of the lung was diagnosed the follow- ing year and seven months later yet another prirnary,, this time adeno- I earcinoma of the kidney, was detect- 'ed. There is a possibility that these multiple primaries, particularly of the skin surface, may be associatedi with high doses of potassium arsen- .ite°'' and that t'he effect of this med- ication is also related to, the lung cancer: Of interest in this respect is the report by Robson and Jelliffe of' six patients who developed'lung can- cer after the therapeutic administra- tionof'arsenic." Cahan made a siin- ilar observationand suggested a pos- sible synergistic action of the arsen- ical compound and cigarette smoke: (oral communication fromlDr. Wil- liam Cahan, Aug 181 1969)' A me- tastatic spread of'the scrotal lesion to the lung, although ai rare occur- rence, is also a possibility,° One exsmoking patient had given up 1'S'years previously after smoking heavily for 22 years. Another patient who had given up smoking 20 years prevsously was a carpenter by trade, an occupation often associated withh lung cancer in nonsmokersl'O 1Nonsmokers With LuRg, Cancer: The fact that Kreyberg 1 lung can- cer can develop in al nonsmoker, though it' is quite rare, needs to be consideredl One of the three non- smokers in the male Kreyberg 1 group was a house painter, I:ike al carpenter, this is an occupation, more common than could be ex- pected among smokers with epider- moid carcinoma of the lung.'° The seeond'nonsmoker was a 54-year-old physician who received excessive nitrogenand sulfur mustard gas ex- posures while working in the Chem- ical Warfare Service in 1942-1946. Really adequate protective elothing ' and' gas masks were not considered very important in those days and on many occasions he suffered blisters and burns on the skin after visiting fields where these gases had been used. The increased occurrence of lung cancer among poison gas work.; ers in Japan is of interest in respect to this case." 'T'he& third' nonsmoker with epidermoid lung cancer was an archaeologist. Comment The findings of the present study in respect to filter cigarettes are con- sistent.with the hypothesis presented in the beginning of the communica- tion. Figure 4' shows the decline in! tar content in~leading filter and nonfilter, brands' of cigarettes: 1958 as well as the increased share of the rnarket taken by filters in this period. These are interesting observations since at the beginning of the 1950's, filter cigarettes represented only a very small fraction of the total con- sumed in the United States. Conceptually, lung cancerdeveI-ops when the cumulative tar dose has reached a certain level: If the dose in a singie cigarette is reduced by 20%, it would be reasonable to assume that to achieve the criticali dose level, the individual would'have 2226I J,AMA, Sept 28, 1970, • Voi 213. No 13 to smoke more cigarettes. The Hammond study on, ex- smokers aged 5o,fi9 years who had smoked 20 or more cigarettes daily, shows that after ten years of not smoking,, the individual§ have a death rate frorn lung cancer similar to that of nonsmokers.' After five to nine years, when Hammond's study shows a decline of 50% among ex- smokers, a similar change as found for filter smokers in the present study, can be expected if smokers change to a lower tar cigarette. On the basis of Hammond's study and our hypothesis, no change would be expected among heavy smokers aged'50-69 years who shifted to filter cig-, arettes and smoked them for five •years or less. 'I'he Hammond study showed'also that exsmokers who had been light smokers (1-19 cigarettes per day) already had a reduced lung cancer risk one to four years after stopping relative to those who had continued smoking. Similar findings were observed by Doll and Hill' The present study did not contain suf- ficient exsmokers to carry out a sep- arate analysis of those who had smoked less than 20 cigarettes' per day and who were under 50 years of age. As none of the lung cancer patient5 in: the present study started out smoking filter eigarettes, the relative risk for individuals who smoked only filter cigarettes could not be deter- ~y mingd. O From an, experimental point of O view, few of the longrterm filter ~ smokers in the study - usedi filters Q that would have selectively removed N components toxic to the cilia from ~i the gas phase, such as hydrogen ~ cyanide andi volatile aldehydes. Cellulose acetate fibers from which ~ , the vast majority of' filters are W made; tend to remove selectively some acidic components ~fromismoke. Since available filter materials gen-, era'lly do not selectively remove car- cinogenic agents from the particu- late matter and the tar from filter cigarettes has the same tumorigenic

activity as tar from nonfilter ciga- rettes when compared on a gram-to- gram basis,!" the decreased risk for filter smokers shown by the present' stvdy appears to relate primarily to the reduction in the total tar con- tent obtained by using filter cigar- ettes: There isa a considerable range in the tar yields of' different filter cigarettes. Therefore, the decreased risk for filter smokers is likely to be in direct proportion to the tar con- tent ~ of various brands. This aspect -_; will be explored in subsequent studies. Through manufacturiisg changes, the tar content of regular nonfilter cigarettes has also been reduced' in recent years so that the present-day nonfi4ter cigarettes should also: be '. relatively less harmful, than they were in the past. This fact may ac- count for the finding that liung, can* cer patients who smoked' nonfilter cigarettes only in the present study tended to have smoked'more of'them than lung cancer patients in the per- lod 194840:' In the study by Wyn- der and Graham in 1950, 220.3% of' • _ : male patients with squamous cell ~ carcinoma of the lung smoked, 35 or more cigarettes or equivalent per day (in these calculations, the data on pipe and' cigar smoking was translated into cigarette equivalents and added to1 number of' cigarettes smoked), while in the present study 49.4%; of nonfilter smokers with Kreyberg 1' lung cancer consumed 35 or more cigarettes daily. It is still unclear, however, wheth- er the decreased relative risk of lung cancer for smokers of contemporary cigarettes compared with 20, years ago is related exclusively to differ- ences in tar yield or also to a reduct- ion in carcinogenic activity of the tar. Animal studies ~ suggest that the latter may also be~a factor. Through the increased use of lower tar yield- ing and homogenized tobaccos, and tobacco st'ems, the tar yield can be diminishedl partly by enhancing combustiom Su& practices haven been shown to leadi to a deerease in. tumorigenic activity of the resulting tars:01 It is to the further, reduction of t'he carcinogenic materials in to- bacco smoke that future researeh ef- forts should be directed.. I3istolog,icGonsiderations.-In, view of' the varying histological in- terpretations of lung cancer sections by different pathologists, a precise evaluation of epidemiologic back- ground for two groups of lung cancer patients is difficult even when the data has been collected and reviewed at only one hospital. However, the results of this study are consistent with previous publications suggesst, ing that though both Kreyberg 1 and 2 lesionsi reiate to cigarette smoking. there are certain epidemiological differences between the two groups. In a Kreyberg group, the male to female sex ratio is greater, the sub- jects smoke significantly more and there are fewer nonsmokers. A male Kreyberg 11 group, also tends to be older and includes a lower percent.e age of Jews than a male Kneyberg 2' group. These differences may bebe- cause the cells that convert to Krey- berg 1]esions have a greatersensitiv- ity to exogenous carcinogens than the cells involved in Kreyberg 2 lesions and alsobeeause of't'he great- er tendency for the latter type of lesions to arise in the absence of exogenous infit7ences. It is suggested: that epiderniologic studies on lung cancer should continue to separate Kreyberg I and 2 lesions.'o Epidemiologic Considerations.- As in all epidemiologic studles„ one must consider a possibility that a person's, reply to questions ma be influenced by bias or error iia recalli Individuals in the present study tended to recall well the brand or brands predominantly smoked. While there was some: switching from, one nonfilter brand to another, or from one filter brand to another, or from nonfilter to filter cigarettes, there were no individuals who, changed back to: nonfilter cigarettes after more than one year on filters.. There may be come error in rerall. of the precise dhration of' filter smoking but' in general we assume that no difference exists in the ac- curacy of recall between the study and control! patients. There is a po- tential bias, however, in smoking histories reported by liing cancer patients because the general popula- tion~ is obviously far better acquaint- ed with the association of smoking and cancer than ten years ago. A Gallup Poll described in the New York Times found, the majority link cigarettes andi cancer (18, 1969). The present study should be re- garded as a preliminary report on continuing efforts to monitor the epidiPmiologic background of' lung cancer patients. However, the find- ings ~ of this study in respect to filter cigarettes are being reported-because they are not only biologically reason- ablw and in line with other findings reported' in a retrospective study in the literature," but also becnuse the results could be of practical! value and justify further efforts to produce less hazardous cigarettes. ©f'course, as in all' epidemiologic investiga- tions, the possibility that an un- known factor or factors, which cor- relat'e with use of filter cigarettes actually provide the correct explan- ation of the difference, cannot bee excluded. For example, those who switch to, filter cigarettes may alsoo inhale less and it may be the reducedl inhalation rather than the decreased, tumorigenic activity of filter cigar- ettes t'hat accounts forthe difierence. Only further investigation can clari- fy. t'hese. issues. Subsequent epidemiologic investi - gations in this area will have to con- tain a far larger number of subjects so that the risk by various types of cigarettes, ie, cigarettes made of dif- ferent kinds of tobacco and with different types of' filters, can be as- sessed. Tar and nicotine levels in any one brand of'cigarettes usually remain parallel so that the risk for smokers of' d'ifferent types of cigar- ettes to develop a variety of diseases, in addition to lung cancer, must~be 0 Lung Cancer-Wynder et al 2227 J0.MA. Sept 28. 1970 r Vol 213, Mo 13

considered. It' is: well known, that cigarette smokers have an increased mortality and morbidity rate~ for myorardial, infarction especially among men under the age of 50 years."' Ih the final analysis, th'ee judgement of' whether one cigarettie's is less harmful' tio man than another cigarette can only be made by mea- suring its long=term effect on man himself. Preven'tive Cons'iderrztions.- ClearIy, the most successful way to reditce the risk of lung cancer is not to smoke cigarettes in the first place or to give up smoking as early in life as possible. While individual motivation to cease smoking, can and has accomp- lished much, the great number of Americans who still smoke cigar- ettes suggests that the large-scale educational efforts against smoking are not likely to be entirely effective. Fon this reason, we must implement deliberate managerial' measures ofthe type classically so successful in solving public health problems im the past to do their share in reducingg the 'risk of lung cancer and'! other' ` tobacco-related! diseases. While in, dividual motivation should be en- couraged more than ever, manager- ia1 preventive measures affecting the entire population of' smokers must be expanded. The undertaking of effective prevention in this area is the responsibility of'all-the gov- ernment, the tobacco industry, the health professions, and the general public. With the burden to effect change placed on the shoulders of society as a whole, it is society thatt will reap the harvest of its actions in years to'come.. Concllusions This study was based'on 3'50 liang, cancer patients seen at the Memor- ial Sloan-Kettering Cancer Center betweenNovember 1966 and August 1969. As in previous studies, cigarette smoking, is strongIy' associated with cancer of'the lung. This association is greater for the squamaus and oat cell tl!pes t'han for the glandular type even though the latter is also related to cigarette smoking, A lower relative risk of lung cancer (Kreyberg, 1 groupY was foun& forr individuals who had smoked filter cigarettes for at' least ten years after switching, from nonfilt'er cigarettes' than for those who continued to saaoke nonfilter cigarettes. Since fil- ter cigarettes tendi to be lower in tar than' nonfilter cigarettes, the results suggest that a reduction in tar yield ofia given strength wilPbe associated' with a'decreased risk for 111ng cancer unless the smoker compensates for the lower tar dosage by smoking more cigarettes." The lung cancer risk for ind'ivi= duals who slnoked' only filter cigar= ettes cannot be determined aC this time. The relative risk for lung, cancer among exsmokers continues to be' high for at least three years' after cessation of smo4ing: Thirteen years after an individual has stopped smoking the relative risk appears to be close to that of individuals whoo never smoked. Further efforts to produce less: harmful tobacco products should' be continued and expanded although not smoking, or cessation of smoking is the most effective prevention against Uung cancer. This studN was supported bv the Ameri- ean Cancer Society urant Ep-i andi in part' by Public Health Service research grant. CA-08748 from the National Cancer, Insti- tute. E. Cuyler Hammond. ScD. and Jerry Comfieid provided statistical adMice in the preparation, o6 this communication. References. 1. Wynder EL Graham EA': Tobaeco smoking as a possible etiologic factor in bronchogenic cancinoma: A study of 684 proved cases. JAMA 143l329a3i8. 1950. 2 Hammond' EC: Smoking in relation to the death rates of 1 million men and women. Nat Cancer Inst .Vlonogr 19:127- 20;t: 1966. 3. Doll R, Hill,AB:, Mortality in rela- tion to smoking; Ten years obeervation ot' British doctors Brit Ued J' 1t1399-1410, 1964. 2228 JAYNA: Sept 28; 1970: • Vol 213, No 13 4..Smoking and Health. Report of the Advisory Committce to the Suraeon Gen- eral of' the f ublic Health Service. Public F$ealthiService. Bulletin 11034 1964. 5. Cornfield J: A method' o( estimating comparative rates from clinicaii data: Ap- plications to cancer of the lung, bremst'andt cervix. J Nat Cancer Inst 11:1269-1275; 195L 8., Montgomery Hi Arsenic as an etiolo- logic aqent: in certain types of'epithelioma. Arch Dernt Syph 32h218-236; 193.5. 7. Neubauer 0: Arsenical'. cancer. A' re- view: Brit J Cancer 1r192-251-19d7. & Robson AD. Jelliffe AM:' Medicinal' arsenic poisoning and' lung cancer. Brit' Med J 2i207-209. 1963. 9. Dean AL: Epithelioma of scrotum. J Llrol 6065f)8-518. 194& 10: Wynder EL. Berg .IW: Cancer of the lung among nonsmokers: Special reference to histologic patterns. Cancer 20:11i61-a172, 196'7. 1'1. Wada S. Yamada A. rlishimoto Y.. et eL• Neoplasms of' the respiratory tractt among poison ttas workers Hiroahima Igaku 16:5fi-7:1. 1963., 12. Wynder E'L Hoflman De Tobacco and Tobacco Smoke: Studiea in E:peri= mental Careinagenesia. New York. Aca- demic Press: Inc, 1967, p 730. 13. Kreyberg L.: Fliutologie Lung,Cancer TYpea:'a Morp4ological and Histological Correlatien, Oi+lo., Norway. I1lotweguan. Glniversit3r, Prese, 1962. 14. Btrosa IDJL Gibson R: Risk of long ancer in smokers who switch ~ to,filter ciga- rettes. Amer J Public HealtA 58:1396.1403, 1968. r' 15. Hyams L Loop A: The epidemi- ology of' myocardial infarction at two age levels. Amer J Epidem 90:93-102, 1969. 16. Pillsbury HC,, Bright CC. O7Connor 1CJ; et al: Tar and nicotine in cigarette smoke: J Assoc Office Agr Chemiata 52: 458-462. 1'969.