TABLE A16.-Experiments concerning the effect of the inhalation of cigarette smoke or its constituents upon the respiratory tract of animals (cont.) (Figures in parentheses represent total number survivors in specific group) Author, war. country, reference Animal A. Type of exposure and B. Duration strain C. Material Results Dontenwill and Golden hamsters. A. Chamber. Number of D&l Wiebecke, c. - B. Up to 4 cigarettes animals average 1966. E. 320 per day for up dead at ezpomre Germany to 2 years. 640 dags (cigaretlea) (77). C. Cigarette smoke. 40 . . . . . . . . . . . . . . 1 40 . . . . . . . . . . . . . . 2 80 . . l-2 143 . . . . . . . . . . .._ . l-4 Comments MET des = desquams- Histologic tive metaplasia. findings in MET branch = bron- dead animals chial papillary 8/ 40 MET des metaplasia. S/ 40 MET des PAP tracb = tracheal 44/ RO MET des (3 MET papillomat* or branch. 2 PAP trseh) intense tracheal 67/143 MET des (13 MET metaplasia. branch. 8 PAP trach) Leuchtenberger CF, mice. A. Chamber. and B. Up to 1,000 hours. Leuchten- C. Cigarette smoke, Marked sguanous berger 1966, exposure to in- cell metaplasia Switzerland fluenza virus (percent) (1.54). (PRR). Controls (100) : Male Female Smoke exposed (59) : Male Female Virus exposed (59) : Malt 11.0 Female - Smoke and virus exposed (88) : Male 9.0 Female 29.0 Marked dgsplaaia (percent f 6.0 21.0 - 43.0 54.0 Marked tmnsgression of lung parolchyma (percent) 3.0 13.0 5.0 t1tJ.o t33.0 tEpithelia1 tissues of these animals showed an increased frequency of cellular atypism. The authors concluded that PRB influenza virus may act as a cofactor in malig- nant transformation. TARLE A16.--Ezpo`iments concerning the effect of t//t, inldntion of cigarette smoke 0~ its constituents upon the respiratory fvxct of animals (cont.) (Figures in parentheses represent total number survivors in srxcific group) -~___~~ Animal A. Type of exposure and 13. I)ur*tion Results Comments Author, war. countrv. reference strain Kockey and Mongrel dogs: SPCW, c. 11. 1966. E. l!l. U.S.A. (CBY). ~-~-----~ Aucrbnch Heagle dogs: C. Material .\. Trnrhral fenestra- Sqlcamous tCarcinom* in situ tisl" (IO). Hyprrplnsin metapln- noted in 5 seppnrate NsoI. henz- Influenzn and smoking 165 3 those noted by pyrene aerosol. Leuchtenberger. -~ ~___ TABLE AlG.-Ezpeviments concerning the effect of the inhalation of cigarette smoke or its constituents upon the respiratory tract of cmhals (font.) (Figures in parentheses represent total number survivors in specific group) _____- .___~ ___~ ._____ Author. year, country, reference Animal A. Type of ~XPOSUFP and B. Duration strain C. Material - ___~ ~__~~ -- Wynder et al.. Male C57BL6 A. Chamber. 1%X, mice: 1~. Up to 315 rJ.S.A. (3~7). c. and E.- cinarettes. more than 40. C. Cigarette smoke, nitrogen dioxide, volatile acids and aldehydes fuund in ciza- rette smoke, swine influenza virus. Results comments -___ Cnnclusions: t tResults not provided No squamous cell respiratory cancer noted. This is attributed in tabular form. to the limitation of inhalation time (CO and nicotine acute effects) and to the anatomically and physiologically intricate nasal passn~e defense system. Expusurr to cigarette smoke, NOZ, or wlatile wide and alde- hrdes leads to reactive hypewlasia and metaplasia, both of which wcw nrjted to be reversible. Swine influenza virus esposurc produced hyperplastic and metaplastic effects which could not be enhanced by subse- quent cx~osu~e to cigarette smoke. Laskin et al.. Rats: A. Chamber. Squamous cell 1070, c. 45. B. 1 hour per day ISL?)msir,e Number carcinoma8 U.S.A. (1%). E. 3. for up to Atmospherr controls . . 3 o/ 3 680 days. Atmnrphcrc plus benzo(n)- c. Benz0 (a) pyrene pyrcnc exp0sure 21 2121 aerosol, so, so, rontlols 3 o./ 3 atmosphere SO, plus benzo(a)- (3.5 P.P.rn.). pyrene exp,E"rr 21 5121 ____-. -._____ Hammond Heagle dogs. See text See tex1. et al., 1970, U.S.A. (II!?). TABLE A21.-Outline of retrospective studies of tobacco use and cancer of the larynx Author, ye==. country, reference CiWZS Controls - Collection of data St?X Number Method of selection Number Method of selection Schrek et al.. 1950. U.S.A. (246). M. 73 Referrals from V.A. hospitals in "entire midwest" to V.A. Cancer Center, Hines. Illinois, during 1942-44; patients with larynx-pharynx tumors clinically or his- tologically diagnosed: Percent Nonsmokers . 13.7 Cigarettes 79.6 Cigars _. 3.7 Pipes _. _. 6.8 522 From same set of referrals. patients Random sample of 6.003 with tumors other than lip, lung, lar- admissions; question- ynx-pharynx: naires from Hines re- ferrals for 1942-44; records included Percent smoking history. Nonsmokers _. _. 23.9 Cigarettes . . . 63.2 Cigars . . . . 10.0 Pipes __. ,_, . . . . . 11.6 Valko, M-F 226 Clinic patients with cancer of the larynx: 108 Clinic patients of same age group with Medical history and pues- 1962. other diagnoses: tionnaire in clinic. Czechoslovakia Percent Percent (Pi%?). Nonsmokers . . 7.6 N onsmokera . 22.2 Cigarettes _. . . . . . . . . . 83.2 Cigars . . . . 4.4 Pipes _. . . . . . . . 10.6 Sadowsky et al., 1963, U.S.A. (P9B). M. 273 White male admissions to hospitals in New York City, Missouri. New Orleans, Chicago; patients with diagnosed laryn- geal tumors. 1938-43: Percent Nonsmokers _. _. . 4.0 Cigarettes only . . 60.1 Cigars only . 2.2 Pipe only . . 4.8 Some combination . . . . . 28.9 616 From same set of admissions, patients Sample of 2.605 out of with illnesses other than cancer: 2,347 interviews (in- cluding smoking his- tory ) by trained lay Percent interviewers. Nonsmokers 13.2 Cigarettes only . . 63.3 Cigars oniy . . . 3.4 Pipe only . . . . . 7.0 Some combination . 23.1 TABLE A21.-Outline of retrospective studies of tobacco we and cancer of the larynx (cont.) Author. year. C*XS countrY, Controls reference S&X Number Method of selection Number Collection of data Method of selection Bliimlein, M. 241 Clinic patients with cancer of larynx: 200 Patients with no laryngeal disease: Personal history taken in 1956. Percent GY"8llY Percent clinic. Patients and Nonsmokera . _. 0.8 Nonsmokers _. _. 18.0 controls -aver 40 years (26). Heavy smokers 79.3 Heavy smokers 4.3 of age. Inhalers 95.0 Inhalers _. 17.0 Wynder et al.. M. 209 White male inpatients Memorial Cancer 209 Patients with other than epidermoid Trained lay interviewers. 1956, Research Center during 1962 to 1954. ClNlCW, U.S.A. ($12). individually matched controls with benign or malignant epidermoid in same institutions: tumors of larynx: Percent Pwcent Nonsmokers _. 0.5 Nonsmokers 10.5 Cigarettes X6.0 Cigarettes _. 13.7 Cigars 7.5 Cigars 10.1 Pipes _. 5.0 Pipes _. 3.8 Cigars/pipes . _. _. __ _, 1.0 Cigars/pipes _. ._ /. 1.9 Wynder et al.. M. 132 Laryngeal cancer patients at Tata Mem- -. 132 Controls individually matched as for Interviews for smoking 1956, orial Hospital, 1962-54: U.S.A. data above: India (.sfZ). and medical histories. Percent Percent Nonsmokers . 13.6 Nonsmokers _. _. 30.3 Bidis _, _. `78.8 Bidis 62.1 Cigarettes _, _. . 5.3 Cigarettes __ 4.6 Hookah _. 1.6 Hookah _. 0.8 Chilum . . 0.8 Chilum 2.3 Schwartz et al.. M. 121 Patients hospitalized from 1954 through 242 1957, Same time and sources; patients hospital- Cases and controls indi- 1956 with laryngeal cancer. in Paris ized for non-cancerous conditions or France (248). vidually matched within and other large cities: trauma: institutions; each mem- Percent Percent ber of a set questioned Smokers 96 Smokers (p20 cigarettes per day 23.4 >20 cigarettes per day . , 18.6 when smoking is con- trolled. -~ _____~ Wynder et al., M. 543 Patients with cancer of oral cavity: 207 Patients with cancer of other sites and 1957, F. 116 232 benign diseases: U.S.A. (SIS). Percent Perce?l t Male Female Mals Fcmnlr Nonsmokers 3 47 Nonsmokers 10 70 Cigars _. . 20 - Cigars _. _. 13 - Pipes . . . 11 - Pipes 6 - Mixed _. R - Mixed 8 - Chew _. 17 - Chew H - Cigarettes 57 53 Cigarettes 63 30 >35 cigarettes >35 rivarettes per day 29 - per day -~ 17 >I6 cigarettes >16 cigarettes per day _. - 34 per day 11 - ~~~..._~ Schwnrtz et al., M. 332 Hospital patients with cancer of oral CBV- 60X Hospitnl patients with non-czmcer ill- 1957. ity and pharynx: ness and accident CISCS. matched by France (248). *ge: Percent Perccn t Nonsmokers 16.4 Nonsmokers 23.4 Cigarettes only 62.7 Cigarettes only 58.2 Pipes only . . . . . . 3.3 Pipes only 3.0 __- ~-~ w L TARLE A28.-Ozctlinc, of retrospcctirlc studies of iol~ctccr~ I(SP red cunccr of the oral cnvitg (conf.) (Data obtained from patient interview and other sources) Author, Yt?ZW, country, reference Cases Controls ___ .-~ __._____~ -~ Srs NUl?lb?l Method of selection Number Method of selection COl""lC"tS Wynder et al., 1951, Cuba (8.25). -__ M. , Ii': Hospital rlinic Datients with cancer of 220 Patients in same clinics with non-malig- F. :34 I,L.RI cavity and pharynx: 214 nnnt conditions, matched by sex and age: PCTCtXlt Percent Male F~malc Male Female Nonsmokers 4 24 Nonsmokers 16 66 Cigarettes Cigarettes jtreduminantly 45 62 predominantly . . 45 21 Cigars predominantly 33 12 Cigars predominantly 22 6 Wynder et al., M. 115 Male patients with cancer of oral cavity 115 Male patients in same hospital with can- Alcohol data significant 1957, and pharynx: cer of sites other than oral, pharynx, only for hypopharynx. Sweden ( 822 ) larynx. lung, esophagus, breast: PeTcent Pdrcent Cigarettes 36.6 Cigarettes 36 Cigars _. . 13.0 Cigars . 9 Pipes . . 12.2 Pipes . . . . 16 Mixed _. _. . . . 15.7 Mixed _. 13 Peacock et al.. 1960, U.S.A. (210). M. F. 25 Hospital r>atients with oral cancer: 14 Patients in same hospital without oral 20 72 cancer and 111 male and 100 female out-patients. randomly selected. Percent 32.6 percent of first group, and 43.3 per- Chewed or used snuff over 20 cent of second group chewed or used years (all patients) . 56.6 snuff over 20 years. Staszewski, 1960, Poland (259). M. 3R3 Male patients with oral cancer: Percent Nonsmokers . _. _. 5.7 "Heavy" smoking index 72.8 Cigarettes only . 72.3 Pipes and/or cigars . 12.8 912 Male patients with other cancerous and non-cancerous conditions: Percent Nonsmokers . . . 17.3 "Heavy" smoking index . . . 49.0 Cigarettes only 60.5 Pipes and/or cigars 11.1 TABLE A28.-Outline of retrospective studies of tobacco MSE and cnmw of tlic ora1 cnvit!! (coTat.) (Data obtained from patient interview and other sources) Author, year, country, reference Vogler et al.. 1962. U.S.A. (698). Cases Controls Comments S-X% Number Method of selection Number Method of selection .__ M. 188 Clinic patients with cancer of lip and oral 521 Patients of same clinic with other can- t Due to varying tabular E'. 92 cavity: 1,064 cer or non-malignant conditions: treatment of data, per- Percent centages of tobacco Male Fsmale users are not all based Chewers _. $32.9 - Percent on the same number of Excessivechewers 22.9 - Male Fern& eases. Snuff dippers - . 72.0 Snuff dippers t6.1 Excessive snuff dippers - 41.3 Tobacco users . 90.0 90.0 Tobacco users 56.0 56.0 Vincent and March&s. 1963, U.S.A. (997). M. F. 66 Successive patients with lesions of buccal 16 cavity and oropharynx: Percent Od OTO- Males : Cavity pharynz Nonsmokers 3.0 - <20 cigarettes per day t. 1X.3 15.1 >20 cigarettes per day 78.1 84.9 Females: Nonsmokers 55.5 26.6 <20 cigarettes per day - --~ >20 riaarettes per day . . ._ 44.5 71.4 100 Successive patients attending gastroin- Male patients used con- 50 lestinnl clinic, age-matched: siderably more alcohol than male controls. Data refers to all forms Pcrccnt of smoking expressed 27.0 as cigarette equivalents. t`icawttt. equivalents: 24.0 1 cigar r= 5 cigarettes 1 Pipe = 2 cigarettes 4!l.O t BN-Betel nut. R2.0 8.0 10.0 __---- - H TABLE A28.-Outline of retrospective studies of tobacco use and cancer of the oral cavitsf (Cont.) (Data obtained from patient interview and other sources) Author, Year. Cases controls c0untl-Y. Comments reference Sex Number Method of selection Number Yethod of SelEetion Sbantr and M. 662 Patients with oral and phawngeal eaneer 300 Controls residing in Krishnamurthi, F. 206 (unsure of confirmation) : 100 same area matched 1964, Percent for we. sex, and India (I&?). BlLCCd Anterior P0&rio+ ehas: Males: Lip mueomz tongue tongue Phownz males No tobacco habit - 2.0 7.2 2.0 6.3 89.1 Smokers 50.0 46.7 66.6 76.0 72.8 62.7 Number of eases . (12) (293) (69) (48) (130) (800) Females: Fanal@ No tobacco habit . . . 14.3 11.0 33.3 - 40.0 88.8 Smokers . . . . . - 4.7 - 8.8 - Number of cases (7) (162) (Iif (4) (26) (100) Wahi et al.. M. 589 Patients with oral and pharyngeal car- 689 Patients matched for age, sex. religion, 1966. F. 232 cinema: 232 and social class. India (sOa). Percent Pwcent Nonsmokers . . . . . . , . 9.62 66.6 Smokers . . . . . . 17.06 21.2 Chewers (Betel nut) . . . . 86.44 6.9 Both . . . . . 37.88 6.4 Hirayama. M. 369 Patients with oral and pharyngeal card- 277 Patients with other (unspecified) dis- Found only a suggestive 1966, F. 176 IUXllP.: I63 eaws: association between Central and Percent Pemmt alcohol-drinking and South East Male Female Male Female oral cancer in non- Asia ( 1 24) Nonusers . 1.6 2.6 17.0 33.0 chewers only. Smokers . _. . 17.1 2.6 23.3 1.2 t BN-Betel nut. Smokers. tBN and tobacco chewers 46.7 6.6 24.9 1.8 TABLE A28.-Outline of retrospective studies of tobacco use and cancer of the oral cavity (cont.) (Data obtained from patient interview and other sources) Author, year. country, reference - Keller, 1967, U.S.A. (140). CSS.3 Controb Sex Number Method of selection Commenta Number Method of selection M. 408 Patients with waumnow cell cw&uxna of 406 Next male patient admitted to same hos- Excessive alcohol con- oral cavity and oropharynx confirmed pita1 within 5 year we range. aumption noted for histologically. Three New York City VA c*spJ involving floor, Hospitals 196368: meaophwynx. and Percent Percent tongue. Nonusers , . . . . . . . . . . . . . 6.1 14.2 Findings indicate tbe Cigarettee . . . . . . . . . . . . . 68.6 66.4 (p