TABLE A14.--Espcrinrents concerning the eflect o/ cigarette smoke on pulmonary surfactarlt and sttrface tension Author, U.S.A. (tzb) do&r lungs. Control . 11 cc.7 I 60 Smoke 10 ,5,a (P/,0.002) I 0 a4 E / I---- l- TAULD A16.4tudies concerning the relationship of smoking to infectioue rewiratory dieeaee in humans (ACLU&I number of CB.I~ shown in parenthmcs) Shl -` Smokerl NS = Nonamokcra AUhX, Ye&r, eountrY. Number wd tY9e of Data couectlo"~ xteauh Commcntd rerrrPnei DOpUhtiO" MU, 118 mnlc mnd HOLJplbl C.WC# Controls The suthor st~lcd that 1960, fcmde patienb Intel-dew. hlcan cue ,,,................ I........%. 49.6 49.6 thcru xl~y n U.S.A. with pneumanlm NS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.26 26.21 algnificnnt diflcrnce (1.57). and 412 hwlthy Cigarette3 only .,.... . ,........ , . . . . . . . . 63.66 62 33 in toboer usage lndlvidurla from Mixed ..,,. I . . . . . . . . . . . . . . . . , . . . . ,.h. 21.19 22.46 between the "random" SU,-&. two groupl. LOW, 620 male and Interview by Nolc* FC%lalC8 Clgnrettc smokers 1966, 186 frmsle trained C,lJCC COnttd# COCI control4 Include pipe amokrrs. England tubercdds social NS ,,,,,.....,........., 2.6 8.1 31.3 61.4 The author noted a (157). patIenti and 419 worker. Cwarettes/day: 1-S . . 8.2 12.9 20.6 21.7 .igniAcnnt drncirncy male and 249 10-19 . . . . . . . . . . ...* 38.1 35.6 30.8 20.6 of non- and light female control 20-29 . . . . . . . . ..I.... 29.4 27.4 smokers and an outpstienh. 30-39 .,............. 11.3 9.3 11.4 2.4 excr,, of hruvy >4o I.,.,.....I.,..... 0.4 6.7 I amokcrr among the C,,~PI Dowllng, Indlvidurrb et al., UDOd t.0 1967, "Infectious U.S.A. cold agent" (751. and plncebo. Interview and medical cxaminatlon. Expored to placebo Ezporcd to infrcliour lioenl No stitlaticnllY Pcrcmt Pcrccnt aigniftcnnt dewloping drurloping dilTrrrnccs A'umbcr "cold" Numbnr "cold" noted. NS . . * . . . . 111 10 928 34 Shl . . , * . 78 14 248 36 TABLE AlS.-stt(die8 conceming the rck~tionsltip of smoking to in/eclio~ts respiratory disease in hwllan8 (Cont.) (Actunl numbrr of ~OIICJ ~huwn in wrrnthraca) SM = Smokers NS = Nonamokcra AUt.hX, yc*r. Number and Dnts country. type cl collection ncaults Comments rclcrcncc gopulation Bcakc. Parc"tT3 of Interview Number of No statidtlcslly 1068, 69 famillm Prrr'm- rcrpirotofy IUrutrcr/ aipnificont U.S.A. lltL%r, iuncsctc gtrrm.yrarr diflerenccu ($5). NS . ..I.. . . . . . . . ,.. (24) 120 624 6.2 natcd. Ciraretti/day: I-10 . ,...... (19) BB 629 6.8 11-20 . . . . . . . . . . . . . . . . . (26) 108 486 4.6 >20 . . . . . . . ..~............ (IQ) 89 424 4.8 Pipe, clnnr . . ..* .,.. (II) 72 804 4.2 Shah ct al., 19G9, Indla (loa). Tuberculosla Survey, X.ray, Institute and emlhyea. Interview. Author, ye&r, Number nnd colllltiy, type of Dntn rcfcrmce DOPUhtiOn collection Ilrrulls Commrnta Drown 306 mnle und - Interview Smoking habile prior lo diagnorid Data nrrscntcd only et al., irmnlc Tubcwrlour yolicnlc Controlr on Queenrlnnd 1061, tuberculosis (pcrccnl) (percent) aample. Aurtrnlia clinic NS ,...,,....._..,..,,,._..,..,.,.. 9.1 18.0 The authors noted (4). pnticnts. Cignrcttcs/dny: 1-Q . 10.6 16.4 that the 221 male and 10-11 34.3 19.6 aignihrnnt diRcrencc fcrnslc 20-29 . . ..I.. 26.3 26 a bctwecn the outpatienta. 30-39 . . . . 1.2 6.4 potienta and >10 ..,,...........,.........,.,. 6.2 9.1 mntrols ~09 not Pipc5 . . . . . . . . . . . . . .._........ 6.9 4.6 present when the gro"", were matched for alcohol intake. Haynes 191 male Interview Average number of rcapiratory iUncnrerli0 students et al.. prep school (adjurlcd Ior age) 1866. studcntd. AU .OYCIC her U.S.A. All (Joal. AU SCYC~C or combined rrapiratory rrapirotory rcapirotory cpiaodcr EpiaOde4 cpiaoder NS (99) ..,........,....,, 11.1 1.6 0.36 Sbl (92) ., ,.......,...,,,, 20.2 6.1 3.34 Pm-rlcll 41 smoking- Intcrvlew et al.. Median number o/ illnca~cclttudcnt The uthors noted nonsmoker palm and health 1966 AU All that these Of atudtnt numes service Cfintldn rcspirntory other dillercnces were mnLchcd for WC rccorda. (J~J). dirrarcrt illncsrra statistically and parrn~3' NS (47) . . . . . 2.08 2.99 rlgnlfitsnt. xcupntional Shl (47) .,................. 2.64 6.00 t Particularly CILIIS. tracbcitia, bronchitls. and pncumonl~. Author, yI'.r, Number nnd Dntn C"U"lry. WPC of collcctio" Rcvulte rrfercnrc Commcnle DOPUlntiOn rrtrrs 1.496 H~tvard Medical history. Number of viails to rtudcnt health unit for rrspirahy Plneao/atudent t e<0.001. et al.. nnd chart review. (comnic-n colda, pharyngitis. bronchitis. larynoitld, 1967. 310 Radclifle and pt~cumonia-not allrruic rhinilir) U.S.A. atudenta. questionnaire. Harvard Radclife IISY). NS . . . . . . . . . . . . . . . . . . . 1.44 (771) 1.44 (193) Sbl . . . . . . . . . . . . . . . . . . . . tz.27 (726) 2.27 (177) <2 YCRTS amoknl .,,...., 2.00 3-4 .,...,..........,,,. 2.30 >G . . . . . . . . . . . . . . . . . . . 2.60 Finklea 1,811 mule Questio""slrc Iicnw rmokcn-21 pcrccnt more clinicnl IIIIINL)R than nonsmokera: The authors .Iso Cl nl., CUllVgC prior to 20 percent mom twuirinz bed rest than nonsmokers nolcd that: 19c9 dudents. h,lliK/68 Light smokers-10 pcrccnt more clinical Illnc3ma than nonsmokers: U.S.A. (n) Smokrra epidemic ond 7 wrccnt more squiring bed rcat than nonamokcrn (BY). rrhlbltml follow.uu on BcroIwIc morbidity. cvlllPllcc of Incr,,nwd subrlitlicnl A2111KIG8 infcclion. (b) Thcrc wn& no diflcrcncc in tIkcra. N ?l TABLE A16.-Complications developing in the postoperative period in patients undergoing abdominal operations GtWUD CZLBeS Smoken ______.___.......... 300 Linbt Smok m-8 . . . . . . 180 Nmamokcm ._.._.._........ 66 Percent chest clear 41.1 68.4 92.3 PerWIlt brancho- PKCKlt PCk-Cmt p"eaunmdOnir tot*, bronchitis complication atelcctasis rllte 63.0 3.3 58.3 27.1 3.9 31.6 6.0 1.3 7.6 Smokcra _. _. __. . . 23 Light Sm 0 k em . . . . . . . . . . . 62 Nonsmokers . _.. . ._. . . . 518 Souscz: Morton. H. J. V. (172) 60.9 39.1 43.5 17.4 77.5 202 1.6 22.5 88.8 8.1 3.1 112 TABLE A17.--Arterial ozygen saturation before and after operation Arterial oxygen saturation (percentage) 1 94 93 94 . . 2 94 93 94 . . N onsmokers 94 . . . . . . 3 96 93 4 93 90 04 . . 6 94 90 93 . . 6 95 91 89 91 I 92 89 81 89 S mokem 89 . _ . . . . . . . . . . . 8 91 83 86 9 93 91 88 92 10 90 87 88 92 SOURCE: Morton. A. (17P). 256 Chapter 4 Cancer Source: 1971 Amcart, Chapter 4, pages 231 - 384. 257 Contents Introduction ...................................... Lung Cancer ....................................... Epidemiological Studies .......................... Prospective Studies .......................... Retrospective Studies ........................ Lung Cancer Trends in Other Countries ............ Histology of Lung Tumors ........................ Lung Cancer Relationships in Women .............. Lung Cancer, the Urban Factor, and Air Pollution. . _ . Lung Cancer and Occupational Hazards ........ _ ... Uranium blining ............................ Other Occupations ..... _ ... ;. ................. Nickel ...................................... Asbestos .................................... Arsenic ..................................... Chromium............-...........~......-.~. Pathological Studies. ............................. Pulmonary Carcinogenesis .. _ ..................... General Aspects of Carcinogenesis . . _ . _ _ . _ . _ _ _ . Polynuclear Aromatic Hydrocarbons . _ . _ _ _ Kitrosamine Compounds. .................. Pesticides and Fungicides ................. Radioactive Isotopes ..................... Inhibitors of Ciliary Novement _ . . _ . . _ . _ . _ Experimentai Studies ...................... Skin Painting and Subcutaneous Injection. .. Tissue and Organ Culture ............. _ .. Tracheobronchial Implantation and Instillation ...................... Inhalation .................... _ ........ Reduction in Tumorigenicity .............. Summary and Conclusions ........................ Cancer of the Larynx ................................ Epidemiological Studies .......................... Pathological Study .... :. ........................ Experimental Study ............................. Summary and Conclusions .............. _ ......... Oral Cancer _............__..._ ..................... Epidemiological Studies .......................... Experimental Studies ............................ Summary and Conclusions ........................ Page 263 265 266 266 266 270 272 277 278 282 282 282 282 283 283 283 284 284 284 290 290 292 292 293 293 293 293 294 294 301 302 303 303 304 307 307 310 311 x4 315 259 Cancer of the Esophagus ............................. Epidemiological Studies .......................... Pathological Study .............................. Experimental Studies ............................ Summary and.Conclusions ........................ Cancer of the Urinary Bladder and Kidney .............. Epidemiological Studies (Bladder) . _ ............... Epidemiological Studies (Kidney) ................. Experimental Studies ....... _ ........ _ ........... Summary and Conclusions ... _ .................... Cancer of the Pancreas ............................... Summary and Conclusions ........................ References ................. . ....................... FIGURES 1. Lung cancer, Finland and Norway . . . . . . . . . . . . . . _ _ . . . 2. Percent of smoking dogs with tumors . . . . . . . . . . . _ . . . . 3. Percent of lung lobes with tumors in smoking dogs . . . . _ 4. Effects of chronic cigarette smoke inhalation on the 271 300 300 haaster larynx . . . . . _ _ . . . . . . . . . . . . . . . . . . . . . . . . . . 310 1. 2. A3. A4. 5. 6. A7. 8. 9. Lung cancer mortality ratios . . _ _ _ . . . . . . . . . . . . . . _ Lung cancer mortality ratios for males by duration of cigarette smoking . . _ . . . _ . . . . . . . . . . _ . _ . . . . . . . Outline of methods used in retrospective studies of smoking in relation to lung cancer . . . . . . . . . . . . . Group characteristics in retrospective studies on lung cancer and tobacco use _ . . . . . . _ . . . . . . . . . . . . . . . Annual means of total lung cancer mortality and sex ratios for selected periods in Finland and Norway Epidemiologic and pathologic investigations concern- ing smoking and histology of lung cancer . . . . . . . Grouping of pulmonary carcinomas _ . _ . . . . . . . . . . . Tumor prevalence among males and females 35-69 years of age, by type of tumor and smoking category ._......__...._.................... Epidemiologic investigations concerning the relation- ship of lung cancer to smoking, air pollution, and urban or rural residence . . . . . . . . . . . . . . . . . . . . . . Pathologic and cytoIogic findings in the tracheo- bronchial tree of smokers and nonsmokers _ . . . , _ 10. LIST OF TABLES Page 315 315 318 318 319 319 319 322 322 325 325 325 325 267 270 349 355 272 273 360 276 279 285 260 LIST OF TXELES (Continued) (A indicates tcibles located in appendix at end of chapter) 11. Identified or suspected tumorigenetic agents in cigarette smoke _ . . . . _ . _ . . . . . _ . _ . _ . _ _ . . . . . . . . X12. Autopsy studies concerning the presence of radio- activity in the lungs of smokers . : . . . . . . . . . . . . . A13. Experiments concerning the effects of the skin paint- ing or subcutaneous injection of cigarette smoke condensate or its constituents upon animals . . . . . A14. Experiments concerning the effect of cigarette smoke or its constituents on tissue and organ cultures . . A15. Experiments concerning the effect of the instillation or implantation of cigarette smoke or its constitu- ents into the tracheobronchial tree of animals _ . . . X16. Experiments concerning the effect of the inhalation of cigarette smoke or its constituents upon the respiratory tract of animals . . . . . . . . . . . . . . _ _ . . 17. Data on pedigreed male beagle dogs of groups F, L, H,hand N . . . . . . . . . . . . .._.__............... 18. Summary of principal cause of death (days No. 57 through No. 875) in dogs of groups F, L, H, hand N 19. Data on dogs with lung tumors indicating type of tumor and lobe in which the tumor was found . . . _ 20. Laryngeal cancer mortality ratios - prospective studies . . . . . . .._...._.._..............-..._ A21. Outline of retrospective studies of tobacco use and cancer of the larynx . . . _ . _ . . _ . . . . . . _ . . . . _. . . _ X22. Summary of results of retrospective studies of tobacco use and cancer of the larynx _ . . . . . . . . . . . . . . . . . . A23. Number and percent distribution by relative fre- quency of atypical nuclei among true vocal cord cells, of men classified by smoking category . . . . . A24. Number and percent distribution, by highest num- ber of cell rows in the basal layer of the true vocal cord, of men classified by smoking category . . . . 25. Deposition of lGlabeled smoke particles in particu- lar regions of the respiratory tract . . . . _ . _ . . . . . 26. Classification of the five registered stages of epithe- lial changes at the larynx . . _ _ . . . . . _ . . . . . . . . 27. Oral cancer mortality ratios-prospective studies. . A28. Outline of retrospective studies of tobacco use and cancer of the oral cavity _ . . . . . . . . _ . . . . _ . . . . . . A28a. Summary of results of retrospective studies of smok- ing by type and oral cancer of the detailed sites.. PCaa 291 361 363 369 372 375 296 297 298 304 380 384 385 386 308 309 312 387 394 261 30. X31. :31. 36. LIST OF TXBLES (Continued) (=\ indicates tables located in appendix at end of chapter) Experimental studies concerning oral cnrcino- genesis __..__._..._.__......._........_.... Esophageal cancer mortality ratios-prospective studies _ . , . . _ _ _ _ . . . . _ . . . . . . . . _ _ . . . . . . . . . . . . Summary of methods used in retrospective studies of tobacco use and cancer of the esophagus . . . . . . Summary of results of retrospective studies of to- bacco use and cancer of the esophagus . _ _ . . . . . . At:-pical nuclei in basal cells of epithelium of esoph- agus of males, by smoking habits and age . . . . . . At)-pica1 nuclei in basal cells of epithelium of esoph- agus of males, by amount of smoking and age . . . . Kidney and urinary bladder cancer-prospective studies _ . . _ . . _ . . _ . _ _ _ _ . . _ _ . . . . . . . . . . . . . . . . Summar)- of methods used in retrospective studies of smoking and cancer of the bladder _ . . . . . . . . . . Summary of results of retrospective studies of smok- ing and cancer of the bladder . . . . _ _ . . . _ _ _ . _ _ Pancreatic cancer mortality ratios-prospective studies . . . . . _ . _ . . _ _ _ _ . . . . _ . _ . . . _ . _ . . . . . . _ . . Pwgc 397 316 401 404 405 406 320 407 409 324 262 INTRODUCTION During the early years of this century, a number of pathologists and clinicians reported a dramatic increase in the incidence of lung cancer. Autopsy studies and studies of lung cancer death rates re- vealed a significant increase beginning prior to World War I and continuing during the ensuing years. This epidemic of lung cancer continues to the present day, with nearly GO,000 deaths expected from this disease in the United States during 1970. Beginning in the 1920's, a number of reports appeared which suggested a relationship between lung cancer and tobacco smoking (2, 30.3 , 278). Since that time, many clinical and epidemiological studies have been published which confirm this relationship. The 19G-l Report (-391) contains a thorough review and analysis of the data available at that time as well as an excellent discussion of the considerations necessary for their evaluation. Xajor epidemiological studies have demonstrated that smokers have greatly increased risks of dying from lung cancer compared to nonsmokers. An increased risk of lung cancer has been found for every type of smoking habit investigated, but two character- istics of the risk are particularly evident: The risk is much greater for cigarette smokers than for smokers of pipes and cigars, and among cigarette smokers a dose relationship exists. That is, the more one smokes, as. measured by total pack-years of smoking, present level of smoking, degree of inhalation, or age at start of smoking, the greater is the risk. It has also been shown that the risk of lung cancer among ex-smokers decreases with time almost to the Ievel of nonsmokers; the time required is dependent on the degree of exposure prior to cessation. Pathologists have found that the squamous cell or epidermoid form of Iung cancer is the most prevalent one in cigarette smoking populations and that this form accounts for a major portion of the rise in lung cancer deaths (15~). Such studies have also indi- cated 3 lower prevalence among smokers for oat-cell and adeno- carcinomas of the lung than for the squamous form, but in most studies a higher frequency of these tumors is found among smokers than among nonsmokers. Smoking has been implicated in the deveropment of other types of cancer in humans. Among these is cancer of the larynx. A num- 263 her of epidemiological studies have demonstrated increased mar- talitY rates for laryngeal cancer in smokers, particularly cigarette smokers, compared with nonsmokers. Autopsy studies have re- vealed that a clear dose-relationship exists between smoking and the development of cellular changes in the larynx, including carci- noma in situ. Cancers of the mouth and oropharynx have been found to be more common among users of all types of tobacco than among abstainers. Although smoking is a definite risk factor in the de- velopment of malignant lesions of the oral cavity and pharynx, its relative contribution in conjunction with other factors such as poor nutrition and alcohol consumption has not been fully clarified. Similarly, although smokers are more likely to develop carci. noma of the esophagus than nonsmokers, the relative additional contribution of smoking in conjunction with nutritional factors and alcohol consumption requires clarification. Smokers have been found to be more at risk for the development of cancer of the urinary bladder than are nonsmokers, and there is evidence to suggest that some smoking-induced abnormal meta- bolic product or abnormal concentration of a metabolic product may be responsible for this increased risk. In addition, cancer of the kidney is apparently more common in smokers than in non- smokers, but the epidemiologic evidence for this relationship is not as definite as for bladder cancer. Epidemiological studies have indicated an association between smoking and cancer of the pancreas. The significance of this rela- tionship is unclear at this time. Experimental studies have demonstrated the carcinogenicity of the condensate of tobacco smoke, or "tar." This material, when painted on the skin of animals, leads to the development of squam- ous cell tumors of the skin. Researchers have shown that this condensate contains substances known as carcinogens, capable of inducing cancers. Among these carcinogens are several chemicals which have been identified as tumor initiators, that is, compounds which initiate changes in target cells and also tumor promoters, or compounds which promote the neoplastic development of initi- ated cells. Other, as yet unidentified, factors are presumably also involved because the sum of the carcinogenic effects of the known agents does not equal that of cigarette smoke condensate. Numerous experiments have been performed in which whole cigarette smoke, filtered smoke, or certain constituents of smoke, such as the "tar," are administered by varying methods to animals or to tissue and cell cultures in order to investigate the neoplastic- inducing properties of cigarette smoke. Particular difficulty has been encountered in experiments which have attempted to deliver whole cigarette smoke to the larynx and into the lungs of experi- mental animals, This has resulted in the use of other methods such as the implanting of pellets containing suspected carcinogens and the instilling into the trachea of suspected carcinogens as such, or adsorbed onto tine inert particulate matter as a carrier. The dif- ficulty with the inhalation studies has been twofold. First, the animals, particularly the smaller species such as the rat, frequently die from the acute toxic effects of the nicotine and carbon monoxide in the tobacco smoke. Second, the upper respiratory tract of experi- mental animals, particularly the nose, is much different from anal- ogous human structures, resulting in a more efficient filtration of smoke in the upper respiratory tract. Nevertheless, in rodents and canines, progressive changes apparently indicative of ultimate neo- plastic transformation have been identified in the respiratory tract. Recently, two studies in different species and in different target organs have been reported concerning the development of early in- vasive cancer following the prolonged inhalation of cigarette smoke; Auerbach and his coworkers (11) trained dogs to inhale cigarette`. smoke through a tracheostoma. After approximately 29 months of daily exposure, these investigators found a number of cancers of the lung. Dontenwill (76) in the second of these two studies, exposed ham- sters to the passive inhalation of cigarette smoke over varying and prolonged periods of time. He observed the deveIopment of pre- malignant changes and, ultimately, invasive squamous cell cancer of the larynx. LUNG CANCER Cancer of the lung in the United States accounted for 45,383 deaths among males and 9,023 deaths among females in 1967 (289). It is presently estimated that approximately 60,000 people will die of lung cancer during 1970. The alarming epidemic of lung cancer is a relatively recent phenomenon. Death rates for lung cancer (ICD Codes 162, 163) rose from 5.6 (per 100,000 resident population per year) in 1939 to 27.5 in 1967 (289, 290). This rapid increase followed the in- creased use of cigarettes among the United States population. The increase has occurred principally among males, although more re- cently females have shown a similar rising pattern. The converging evidence for the conclusion that cigarette smok- ing is the major cause of lung cancer is derived from varied types of research including epidemiological, pathological, and laboratory investigations. 265 EPIDEMIOLOGICAL STUDIES Numerous epidemiological studies, both retrospective and pros- pective, have been carried out in different parts of the world to investigate the relationship between smoking and cancer of the lung. These studies are outlined in tables 1, 2, A3, and A4. Prospective Studies The major prospective studies concerning the relationship of smoking and lung cancer are presented in table .l. In all, these investigations have studied more than a million persons from a number of different populations for up to 10 years. These studies show increased lung cancer mortality ratios for cigarette smokers of all amounts ranging from 7.61 to 14.20 among male smokers as compared to nonsmoking males. The one major prospective study of female cigarette smokers reveals an overall mortality ratio of 2.20 (118). Also uniformly present in these studies is a dose-related increase in the mortality from lung cancer with increasing amounts of cigar- ettes smoked per day. Other measures of exposure show similar trends. Hammond (118) reported increased mortality ratios asso- ciated with increased inhalation (table I) as well as with increased duration of smoking (table 2). Ex-smokers show significantly lower lung cancer death_- .rates than continuing smokers. In their study of more than 40,000 B$tish physicians, Doll and Hill (74, 75) noted a decrease in lung carricer mortality rates with increasing time since smoking stopped (table 1). During the past 20 years, half of all the physicians in Britaig who used to smoke cigarettes have stopped smoking. While the death rates from lung cancer rose by 7 percent among all men from England and Wales during the period from 1953-57 through 1961- 65, the rates for male doctors of the same ages fell by 38 percent (96). Pipe and cigar smokers have been shown in the prospective stud- ies to have lung cancer mortality rates higher than those of Bon- smokers, although these are generally substantially lower than those of cigarette smokers (table 1). Retrospective Studies More than 30 retrospective (case-control) studies have been re- ported conc&ning the relationship of smoking and lung cancer. These studies are outlined in tables A3 and A4. Table A4 presents the percent of nonsmokers and of heavy smokers among both cases and controls as well as the relative risk ratios for all smokers. 26.6 (Actual number of deaths shown in porenthcsn)' Shl= Smokcrn. NS = Nonsmukcra. Author, Number yenr. wdo'qw co'zP Follow- NUmbCr Regular cigarette I'irw EO"rlLl-Y. UP dcaok smoking only cigar Inbalntion Exsmokcrs CDmlliCnt3 reference popuL5tion YcBrl (ciBarctter/day) Hammond 187.783 Queation- 3 `h 448 Pills No dotn fIro,lchoocnic 341l.448 and white nnirc and SN 443 NS ..I.. 1.00 (16) NS .,. ;.OO (16) (Errludinp adcnocnrcinoma) drnth? with IIorn. msles interview. NS , 16 20 . . . . 23.40(\17) NS .,. 1.00 (1G) Continuing . ,,. ,, .16.94 ClUllc-3 t1w,e (110). LDCB All . ..t10.73(397) SII ,,. 1.00 (7) Duration 60-69. 1 I0 yenrs , ( 1.61 amokcrs who PrcviourlV >I pack/day ntv~ amokd Continuing , . .46.21 ply<* und Duretion uf cesrstion 1 lO year* .17.79 w\lh""t micrwcopic vrwf. - Doll and ApprOXi- QucsCion- 10 212 NS ...I 1.00 (3) Pipe and Cigar No data Cigeretlc rmokcrr Hill, mstely naire and SM , 209 l-14 ,.,. 8.14 (22) NS ., . . 1.00 (3) NS . ..I. .,.. .,..... ~. 1.00 (3) 1964, 41,OdO fOllOWUP NS . 8 16-24 ,. .19.86 (63) Groma/dav Continuing t . . . . . . . . . . 18.21(124) Grest male of dcatb >25 . . . . 32.43 (67) l-14.. 6.00 (12) Durnlion <6yettra 9.61 (b) Britnin UriLirb certificate. 15-24 ., 6.43 (G) of 6-9 years 7.00 (7) (70. physiciana >26 .13.71 (3) I c~ssi,tiun lo-20 ycara 2.67 (3) x0 ycrrs 2.11 (2) Beat. APDroxi- Queetion- 6 331 NS . . . . . 1.00 (7) Pipe No dnts 1 II, fcra 1966. mntcly nairc nnd tSM 324 no .I?.31 (63) Cigar Canadian cixorctl~~ only 6.06 (18) cixnrs tic certificate. All .14.?O(ZdG) NS ..I.00 (I) an,ilkLr!d YewranD. SM . ..2.94 (2) only. __~- -. .- TABLE l.--Lung cuttce~ mwtulity rattie (cont.) (Actud number of dcrtha rhown In DWeQthW=)' SM = Smoktn. NS = Nonsmokem. Prodpectlve studies 8% 1,266 sbi .1,118 NS . 7.6 Reguh eiwctte smoklnn only (clparettra/day) PIPS cl&x Inhalhtion Exsmokcn Cammcr NS ,*... 1.00 (78) 1-B *,.. 5.49 (46) lo-20 . , . 9.91 (am) 21-39 . . .17.41(816, >S9 . .a a23.93 (8'2) AU , ,.. .12.14(749) Pip NS . . ..l.OO (78) Nodata sbl *.. .1.84 (17) Cigar NS . . ..l.OO (78) SM . . ..I.69 (6) Pip. and cigar NS . . ..l.OO (78) SM . ...1.66 (20) NS . . . . . . ,....a 1.00 (78) Number of ciparsttoldav: l-9 .,,,. *.*... 0.96 (4) lo-20 . . . . ..I.. l.48 (89) 21-89 .,......* 9.88 (17) >a@ . . . . ...**** 8.24 (19) IU - Hum.nond.440.668 InterviewB 4 Mdu 1966, mbles by ACS 1,169 U.S.A. 662.671 voluntetn. SM .l.llO (Jl6). fer4er NS . 40 w-a4 FOlWh ,e.n of 188 .gt In 26 SM. 81 statea. NS 6 102 Cuncnt ei0aret1cc Pips oh NS . . ..l.oa (49) hfda SM . ...2.24 (21) NS a.... 1.00 (49) Cigar 1-S .*.. 4.60 (26) NS . . ..l.OO (49) lo-19 . . . 7.48 (82) Sbl . . ..1.86 (22) 20-39 . ..13.14(981) Pipe and cioar >40 ,,.. 16.61 (82) NS a... 1.00 (49) AU a.... 9.20(719) SM . ...0.90 (11) Fcmdu NS .,... 1.00(102) l-19 , ., , 1.06 (20) >20 . . . a 4.76 (60) All . . . . . 2.20 (81) Mdecr NS . . . ..s.. 1.00 (43) Slight . . . . . . 8.42(120) Moderate ,a .11.46(811) DWD . . . . . ..14.81(141) FCiVlOL~ ICD cD11c 162 only. NS ,....... 1.00(102) Slkbt ..a... 1.78 (26) 8.70 (46) TABLE I.-Lung cancer mortality ratios (cont.) (Aetusl number of deaths &own in Darcnthpsea)l SM = Smokers. NS = Nonsmokers. Prospective studies Author, Number FOUOW- Year. andoyw Data UP Regular cizzarette Pipe ~0"l-ltl-Y. collection years N"zber smoking only cigar InhalPtlon Exsmokcrs Comment.9 nferenee poPulatlcn deaths (cigarettes/day) nucu 69.868 Question. 3 a04 NS 1.00 et al., Americm naire and <20 ,.,. 2.30 1967. LcpiOW fOllOWUP 20 ,.. 3.50 U.S.A. nsirea of death >20 . . . . 4.90 (AD). 36-76 certificate. ye&l-a of out and older. Hlrw~m~.265.116 TUiW?d 1% 4s NS . . . . . 1.00 (a) rrcllmlnnrr 1067. mnlcand PIIS SM . 40 l-24 . . 2.69 (29) report. Jbpan femnle nurse >26 . . . . 6.68 (6) (lfb). adulb IntervIew 40 ye." and fol- of we and lowuu of older. death ccrtlflcate. ??o? o nd 68.169 Qumtlon- 68 BE8 NS ..a. 1.00 NY Include Dunn. mah In nnlre and 510 ., . 8.12 pipo nnd 1970, V~rloub fOllOWUP 220 , , , 8.06 cigar U.S.A. OCCUP.. of derth >a0 ,. , 9.66 amoken (roa) * tiona in certith(c. AU a.. 7.61 YJI include C~llfOn\lll. cx-amoker~. L Unlm, otbcrai~e mpecifled, disparltlcs between the total number of death8 and the bum of the Indlvldtml amoklng cbtewxies w-e due to the cxclu~l~n r-4 of clthtr ocrralonrl. mlacell~neous, mlxed, or exsmokcra. z TABLE 2,Lung cancer mortality ratios for tit% by duration of cigarette smoking (,4ctusl number of death arc sboan in parenthesa) age began cigareYe smokine 35-64 25 or older _........... 2.77 (6) *Is24 ________......... 6.83 (31) 15-19 .___............ 8.71(112) 25 ,... . . Epidrmloid (475) 0.2 (1) Nalt-l oat-ccl1 BI annplaatia (101) 0.1 (2) 2.9 (IO a.9 (12) 36.6~1c9) ZC.3~11OJ 3C.8 (176) 34.7(10GJ 24 4(lIG) 24.4 (70 Epidcrmoid (18) 61.1 (11) 6.6 (1) 22.2 (4) 6.6 (I) 6.6 (1) FCTllo(C# oat.ccu or an.aphtic (19) 31.6(12) 16.8 (6) 23.7 (0) 18.4 (7) 10.6 (4) Admocarcimmo (IO) blolc~-10G unclaui!X GO.0 (6) t"~O~. Fcmslw-13 unclwifiul 20.0 (2) tumors. 10.0 (1) .,. 20.0 (2) ti -- __.-_-_.-.. z TABLE 6. Epidemiologic and pathologic investigations concerning emokhg and the histology of hg came? (cont.) e (Actual number of can ahown In parenlbcam) Author. Number of et al.. 1967, FWlC-2 (%ll). female cases with hl~tologlcaUy Epidcrtnoid ATUlPhlic Udwwn tvps Cvlindrkd + Difference confirmed Jung crsea . . . . ~ . . . . 96.0 81.0 86.0 100.0 siyniRcant cancer. 4 matched Controls . . 79.0t 83.0t 79.0t 06.0 *t p~O.06 Icvel. control IlwUDLI. Hwn,zel 168 female Relative risk for apccified tumorr (rmokn*/wnrmokera) 134 man with nnnl st .I.. case9 or bialoloaicnl 1968, lung cnrlccr. Grmp I (Xrwbcrg) Admocarciwma determinulion. U.S.A. Adjusted for age and occupation. ,,..,.....I.. 3.0t 1.19 t Diffcrcnce from (ii%). unity aigniRcrsnt8L ll~O.Ol. Haen32el 2.181 mnlc Stnutnrdircd martdilv roliar Cuts obtslncd from t. rrrrrcncc mr, h,Nl Cohen 411 malt and .nd Icmalc CUBY Of Hossain. lung cancer with 1966, histolugic U.S.A. dingnosia 1939-63 Nonsmokera . . . (56). at one husvital. Smokers . and frmule EOHCB of DUVle& hialoloyirslly Unili~crcmlti~tcrl IDGI. dlngnurcd Nonsmokera 2.8 (4) Enulnnd lunn cancer. Pipe . 9.9 (14) (6). Cigarette . . . . . . . . . . . . 87.3(124) ro , *. . . I.. 7.1 (IO) Souvnww 2.6 (G) 9.9 (20 87.6(211) 22.4 (64) 41.6(100) 21.6 (62) 12.9 (31) 6.2 (16) clylllctlc s"wkl,iy Adcnocarcinom P,,,IParl to bc `il 3.4 (2) llronyly rclutcd to 1.7 (1) adcnocsrcillomn 113 lo 94.9(663 (he olhcr 2 tywa. 22.0(13) A~blcy'r data on `.ootul 33.9(20) number of civurcltc 16.9(10) smukrrs BTL' 8.6 (6) inconuistvnl with 6.1 (9) hi3 brcnkduwn ol