ise

TABLE A1l6.—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,

year, Animal A. Type of exposure
country, and B. Duration Results Comments
reference strain C. Material

Dontenwill and Golden hamsters, A. Chamber. Number of Daily MET des — desquama-
Wiebecke, Cc. — B. Up to 4 cigarettes animale average Histologic tive metaplasia.
1966, E. 320 per day for up dead at exposure findings in MET bronch = bron-
Germany to 2 years. 540 days (cigarettea) dead animals chia! papillary
(77). C. Cigarette smoke. 40 tees 1 8/ 40 MET des metaplasia.

40) oe. aes eae 2 8/ 40 MET des PAP trach = tracheal
80 1-2 44/ 80 MET des (3 MET papillomata or
bronch, 2 PAP trach) intense tracheal
148 1-4 67/143 MET des (13 MET metaplasia.
bronch, 8 PAP trach)

Leuchtenberger CF, mice. A. Chamber. Marked tEpithelial tissues
and B. Up to 1,000 hours. transgression of these animals
Leuchten- C. Cigarette smoke, Marked squamous Marked of lung showed an increased
berger 1966, exposure to in- cell metaplasia dysplasia parenchyma frequency of cellular
Switzerland fluenza virus (percent) (percent) (percent) atypism. The
(164). (PR8). Controls (100): authors concluded

Male — _ — that PR8 influenza
Female ..... — — — virus may act as a
Smoke exposed (59) : cofactor in malig-
Male —_ 6.0 3.0 nant transformation.
Female . —_ — _
Virus exposed (59):
Male 11.0 21.0 13.0
Female ..... _ — 5.0
Smoke and
virus exposed (68):
Male ....... 9.0 43.0 t18.0
Female ..... 29.0 54.0 $33.0

 
tse

TaBL_e Al6.

 

Eaperiments 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,
year, Animal A. Type of exposure
country, and B. Duration Results Comments
reference strain >. Material
Rockey and Mongrel dogs: ‘A. Tracheal fenestra- Squamous tCarcinoma in aitu
Speer, CG. 1. tion (10). Hyperplasia metapla- noted in 5 separate
1966, E. 19. Nostril inhala- with sia with Pre- Carci- sites in this
U.S.A. (228). tion (9). Inflam- atypical atypical cancerous noma animal.
BR. Tracheal fenestra- mation features features changes in situ
tion—284 treat- Controls (1!) . 9 1 1 0 0
ment days. Tracheal
Nostril inhalation— fenestra-
180 treatment tion (10)... 10 5 6 1 #1
days. Nostril in-
C. Cigarette smoke. halation (9) . 6 0 0 0 0

 

 

 

 

 

Auerbach Beagle dogs: A. Tracheostoma. Controls, experimental:

etal, C. 10 (2 with B. Up to 12 No histologic change in bronchial] epithelium:
1967, tracheostoma). cigarettes per @. 1 animal died at 24 days and no histologic change noted.
U.S.A, (10). E. 10. day for up b. 5 animals sacrificed at 421 days and nuclear atypism
to 421 days. noted in all.
C. Cigarette smoke. c. 2 animals died at 229 and 278 days and nuclear atypism
was noted but of lesser severity than in those sacrificed at
421 days.

Harris and C57BL mice: A. Chamber. Number of This strain of mice
Negroni, Cc. 200. RB. Smoke—12 ciga- Treatment Number lung carcinomas is noted for its
1967, E. 1,437. rettes per 20 Controls .. 00.0... . eee eee 200 0 lack of spontaneous
England mice for 12 Influenza aerosol alone ..... 682 15 lung tumor formation.
(i121). minutes every Benzpyrene aerosol Animals exposed to

other day for (4 exposures) .......040- 200 2 cigarette smoke
lifetime. Smoking 200 8 (all adeno- showed no hyper-
C. Cigarette smoke, carcinomas) plastic epithelial
influenza virus Influenza and benzpyrene 200 3 changes such as
aerosol, benz- Influenza and smoking ..... 155 3 those noted by

pyrene aerosol,

Leuchtenberger.
ese

Author,
year,

country,

reference

Wynder et al.,

1968,

U.S.A. (327).

TABLE Al6.—Hxperiments 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)

Animal
and
strain

Male C57BL6

mice:
C. and K.—

more than 40.

A. Type of exposure

B. Duration

C. Material

A. Chamber.

B. Up to 315
cigarettes.

C. Cigarette smoke,
nitrogen dioxide,
volatile acids
and aldehydes
found in ciga-
rette smoke,
swine influenza

Conclusions: ¢

No squamous cell respiratory cancer noted. This is attributed

Results

Comments

tResults not provided
in tabular form.

to the limitation of inhalation time (CO and nicotine acute
effects) and to the anatomically and physiologically intricate
nasal passage defense system.

Exposure to cigarette smoke, NO,, or volatile acide and alde-
hydes leads to reactive hyperplasia and metaplasia, both of
which were noted to be reversible.

Swine influenza virus

exposure

produced hyperplastic and

metaplastic effects which could not be enhanced by subse-
quent exposure to cigarette smoke.

 

 

 

virus.

Laskin et al., Rats: A. Chamber, Squamous cell
1970, C. 45. B. 1 hour per day Exposure Number carcinomag
UAS.A. (159). E. 3. for up to Atmosphere controls 3 0/ 3

690 days. Atmosphere plus benzo (a) -

C. Benzo (a) pyrene pyrene exposure 21 2/21
aerosol, so, SO, controls 3 0/3
atmosphere so, plus benzo (a)-

(3.5 p.p.m.}. pyrene exposure ........ 21 5/21

Hammond Reagle dogs. See text See text.
et al.,

1970,

U.S.A. (119).

 
ySEe

TABLE A21.—Outline of retrospective studies of tobacco use and cancer of the larynx

 

Author,

 

 

year, Cases Controls
country, - Collection of data
reference Sex Number Method of selection Number Method of selection
Schrek et al., M. 73 Referrals from V.A. hospitals in ‘‘entire 522 From same set of referrals, patients Random sample of 5,003
1950, midwest” to V.A. Cancer Center, Hines, with tumors other than lip, lung, lar- admissions; question-

U.S.A. (246).

Illinois, during 1942-44; patients with
larynx-pharynx tumors clinically or his-
tologically diagnosed:

 

 

ynx-pharynx:

 

naires from Hines re-
ferrals for 1942-44;
records invluded

 

 

 

Percent Percent smoking history.
Nonsmokers - 13.7 Nonsmokers ........-00 00005 23.9
Cigarettes . 79.5 Cigarettes 2... ... eset eee eeee 59.2
Cigars 3.7 Cigars
Pipes 6.8 Pipes
Valko, M-F 226 Clinic patients with cancer of the larynx: 108 Clinic patients of same age group with Medical history and ques-
1952, other diagnoses: tionnaire in clinic.
Czechoslovakia Percent Percent
(292). Nonsmokers .........-00+05- 1.5 Nonsmokers ........-.----+% 22.2
Cigarettes ........ sees 83.2
Cigars 2.2.2 ee ce eee -. 44
Pipes... cece eee eee 10.6
Sadowsky et al., M. 273 White male admissions to hospitals in 615 From same set of admissions, patients Sample of 2,605 out of
1953, New York City, Missouri, New Orleans, with illnesses other than cancer: 2,847 interviews (in-
U.S.A. (282). Chicago; patients with diagnosed laryn- cluding smoking his-

geal tumors, 1938-43:

Percent
Nonsmokers .......-+-+-eeee+ 4.0
Cigarettes only ............-. 60.1
Cigarsonly ............2005. 2.2
Pipe only

 

Some combination

 

Percent
Nonsmokers ........-+ ... 13.2
Cigarettes only §3.3
Cigars only . . 3.4
Pipe only .......... seeee TH
Some combination .......... 28.1

tory) by trained lay
interviewers.

 
Sse

TABLE A21.—QOutline of retrospective studies of tobacco use and cancer of the larynx (

cont.)

 

 

 

   

 

 

 

 

 

 

 

 

 

Author,
year, Cases Controls
country, Collection of data
reference Sex Number Method of selection Number Method of selection
Blimlein, M. 241 Clinic patients with cancer of larynx: 200 Patients with no laryngeal disease: Personal history taken in
1955, Percent Percent clinic. Patients and
Germany Nonsmokers 0.8 Nonsmokers ...... . 18.0 controls over 40 years
(26). Heavy smokers -- 19.3 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 1952 to 1954, cancer, individually matched controls
ULS.A. (912). with benign or malignant epidermoid in same institutions:
tumors of larynx:
Percent Percent
Nonsmokers ..............., 0.5 Nonsmokers ................ 10.5
Cigarettes Cigarettes 73.7
Cigars Cigars ........ 10.1
Pipes ............ Pipes ......,.. 3.8
Cigars/pipes Cigars/pipes ........... 1.9
Wynder et al., M. 132 Laryngeal cancer patients at Tata Mem- 132 Controls individually matched ag for Interviews for smoking
1956, orial Hospital, 1952-54: U.S.A. data above: and medical histories,
India (S12). Percent Percent
Nonsmokers ................ 13.6 Nonsmokers ................ 30.3
Bidis 22... 0. eee ee 78.8 Bidis ..0. 0... eee eee 62.1
Cigarettes ..0.........0...., 5.3 Cigarettes vee eee eee 4B
Hookah ................0.0.., 1.5 Hookah .................... 0.8
Chilum ..................4.. 0.8 Chilum oo... 2.3
Schwartz et al., M. 121 Patients hospitalized from 1954 through 242 Same time and sources; patients hospital- Cases and controls indi-
1957, 1956 with laryngeal cancer, in Paris ized for non-cancerous conditions or vidually matched within
France (248). and other large cities: trauma: institutions; each mem-
Percent Percent ber of a set questioned
Smokers ................00.. 96 Smokers (p<0.05) 6.00.00... 84 by the same trained lay
Inhalers .................,.0, 58 Inhalers (p<0.05) 47 interviewer.
Roll their own cigarettes .... 44 Roll their own cigarettes .... 31]

 
9SE

TABLE A21.—-Outline of retrospective studies of tobacce use and cancer of the larynx (cont.)

 

Author,

 

 

 

 

 

 

 

year, Cases Controls
eountry, Collection of data
reference Sex Number Method of selection Number Method of selection
Wynder et al., M. 60 Patients at Radiumhemmet with squam- 271 Patients from same source and time, By trained lay inter-
1957, ous-cell cancer of larynx, from 1952 with cancer other than squamous-cell viewers in hospital.
Sweden (322). through 1955: of larynx:
Percent Percent
Nonsmokers ......: ++ ee reeee 5 Nonsmokers ........+.+ 0005 24
Cigarettes... 0. eee eee eee AT Cigarettes 2.0... 2. cece eee 36
Cigars 2.0.2... 2 cece ee eee eee FT Cigars... 6. cece eee eee 9
Pipes ....... 15 Pipes oo. cece ee eee eee eee 16
Mixed 17 Mixed 13
Wynder et al., M. 142 Clinic patients in Havana during 1956-57, 220 Same source and time; apparently pa- Interview of patients
1958, F. 32 with histologically diagnosed epider- 214 tients with cancers other than larynx, in clinic.
Cuba (825). moid cancer of larynx. lung, or oral cavity, matched for age:
Percent Percent
Male Female Male Female
Nonsmokers ......... 1 13 Nonsmokers .......- 16 66
Cigarettes ........... 62 72 Cigarettes 45 27
Cigars ............006 20 6 Cigars 22 6
Pipes .......-.....0.- 1 ae Pipes ....... 1
Mixed .......-.-...+. 16 9 Mixed ............0. 16
Dutta-Choudhuri M-F 582 Patients in Calcutta cancer hospital dur- 288 Not specified Tobacco histories ob-
et al., ing 1950-54, with laryngeal tumor diag- tained during 1951-54,
1959, nosed and confirmed by biopsy or smear: apparently by inter-
India (86). Percent Percent viewer.
Nonusers ........2. 0-0-0005 14.1 Nonusers .... 22. ccc ecco 41.7
Cigarettes or bidi ........... 77.8 Cigarettes or bidi ........... 52.1
Chew 0... eee e eee eee 3.1 Chew 3.8
Both oo. cc eee eee cee eee 5.0 Both 2.4

 

 
LGE

TABLE A21.—Outline of retrospective studies of tobacco use and cancer of the larynx (cont.)

 

 

 

 

 

 

 

 

 

Author,
year, Cases Controls
country, Collection of data
reference Sex Number Method of selection Number Method of selection
Staszewski, M. 207 Patients admitted to chronic disease hos- 912 Patients admitted during 1957 and 1958 Author interviewed pa-
1960, F 13 pital during 1957 and 1958 with histo- 1,813 to ehronic disease center for cancer- tients suspected of lung
Poland (259). logically confirmed squamous-cell car- ous and noncancerous conditions pre- cancer for smoking
cinoma of the larynx: sumably not related to tobacco con- history and background.
sumption:
Percent Percent
Nonsmokers ................ 0.5 Nonsmokers ................ 17.3
Cigarettes only . 87.9 Cigarettes only ............, 60.5
Pipes and/or cigars .......... 1.9 Pipes and/or cigars . 11.1
“Heavy smokers” . 88.4 “Heavy smokers” ........... 49.0
Inhalers ..0... 2... eee, 96.1 Inhalers ..... 0.0... cee es 66.8
Female smokers ............. 30.8 Female smokers ............ 8.4
Rozenbilds, M. 191 Patients admitted to 3 major hospitals No controls. Patient interviews.
1967, F, 21 with cancer of larynx and hypopharynx:
Australia Percent
(229). Nonsmokers ................. 8
Smokers .............02.00.08 92
Heavy smokers .............. 30
Terraco] et al., M. 961 Private service and clinic patients of ENT No controls. Patient interviews.
1967, hospital:
France Percent
(274). Nonsmokers 12.1
Smokers .....0.......000000, 87.9
Svoboda, M. 205 Patients admitted to a regional hospital 320 Male controls Cases: patient interviews.
1968, F. 10 over a period of 6 years all confirmed Controls: not stated.
Czechoslovakia histologically: Percent
(271). Percent Nonsmokers ..............0. 22.0
Nonsmokers ................ 2.93 Cigarettes (approximately) . 71.0
Cigarettes ....... 0.00. cae 94.63 Pipes (approximately) ...... 7.0
Pipes ...... cee eee e ee eee 2.44

 
TABLE A22.—Summary of results of retrospective studies of

tobacco use and cancer of the larynx
(Figures in parentheses represent ratios based on less than 5 case nonsmokers. }

 

Relative risk ratio} ali

 

  

Investigator reference smokers to nonsmokers
Schrek et al., U.S.A. (246) 00 ee et eee tet nees 2.0
Valko, Czechoslavakia (292) ........, Veen eee eee ene erences 3.5
Sadowsky etal., U.S.A. (282) ooo te eee eens 3.7
Blimlein, Germany (26) ........... 27.5
Wynder et al., U.S.A. (372) 23.6
Wynder et al., India (312) bees beeen ee tees 3.1
Schwartz et al., France (248) 00. eee tt eee eae 4.6
Wynder et al., Sweden ($22) 0. c eee e eee 6.0
Wynder et al., Cuba (325) 0... cc ee ee ee eee eee nee (18.9) (males only)
Dutta-Choudhuri et al., India (86) 00... ee ree 4.3
Stazewski, Poland (259) 0.00... cc ce tree eens (40.0) (males only}
Svoboda, Czechoslavakia (271) 2.00... cee ce ee ee eee 8.3

 

1 Computed according to method of Cornfield, J. (67).

358
6S

TABLE A23.—Number and percent distribution by relative frequency of atypical nuclei

among true vocal cord cells, of men classified by smoking category
(100 percent atypical cells defined as carcinoma)

Current cigarette smokers

 

 

 

 

 

Percent Never smoked Ex-cigarette Cigar/pipe Less than 1 1-2 packs 2 or more
atypical nuclei regularly smokers smokers pack a day a day packs a day

Num- — Per- Num- Per- Num-_ Per- Num- Per- Num-  Per- Num-  Per-

ber cent ber cent "ber cent ber cent ber cent ber cent

Total oo. eee eee 88 100.0 116 100.0 94 100.0 125 100.0 329 100.0 190 100.0

None oo... 0. ccc ccc eee eee eens 66 75.0 86 TA 1 1.1 1 8 0 _ 0 _

Less than 50 8 9.1 14 12.1 4 43 25 20.0 4 1.2 0 _

50-59 10 11.4 13 11.2 50. 53.0 54 43.2 87 26.4 29 15.3

60-69 4 4.5 1 9 23 24.5 21 16.8 116 35.3 16 39.4

70-79 0 _ 2 1.7 9 9.6 9 7.2 44 13.4 38 20.0

80-89 0 _ 0 —_ 2 2.1 2 1.6 19 5.8 11 5.8

90-99 0 _ 0 _ 1 11 0 — 5 1.5 0 _
100:

Carcinoma in situ ..........000. 0 — 0 — 3 3.2 13 16.4 52 15.8 35 18.4

Invasive carcinoma ............ 0 - 0 ~ 1 1.1 0 — 2 6 2 11

 

Source: Auerbach, O. et al. (9).
O9e

TABLE A24.—-Number and percent distribution, by highest number of cell rows in the
basal layer of the true vocal cord, of men classified by smoking category

 

Current cigarette smokers

 

 

 

 

Number of Never smoked Ex-cigarette Cigar/pipe Less than 1 1-2 packs 2 or more

cell rows regularly smokers smokers pack a day a day packs a day
Num- Per- Num- Per- Num- Per- Num-  Per- Num-_ Per- Num- Per-
ber cent ber cent ber cent ber cent ber cent ber cent
i 0) 0 88 100.0 116 100.0 94 100.0 125 100.0 329 100.0 190 100.0
Less than 5 cell rows ......0----0-5 30 34.1 7 6.0 4 4.3 3 2.4 1 0.3 0 a
BecellrowS 0.2... cee eee ee eee eee 29 33.0 27 23.3 20 21.8 27 21.6 38 11.6 20 10.5
6 cell OWS . 2.0... ee cee ee eee 8 9.1 15 12.9 15 6.0 25 20.0 51 15.4 24 12.6
Teel] rows 00... .e cece eee eee ry 6 6.8 12 10.3 18 19.1 12 9.6 38 11.6 19 10.0
Beell rows .... 6. eee eee eee 8 9.1 14 12.3 9 9.6 13 10.4 30 9.1 23 12.1
9 cell rOWS 2... ce eee ee eee eee 1 11 7 6.0 q 7.4 6 4.8 26 1.9 14 TA
10 or more cell rows .....-.-..2-0 0505 6 6.8 34 29.4 2t 22.3 39 31.2 145 44.1 90 AT.4

 

Source: Auerbach, O. et al. (9).
L9E

TABLE A28.—Outline of retrospective studies

Author,

of tobacco use and cancer of the oral cavity

(Data obtained from patient interview and other sources)

 

 

 

 

 

 

 

 

year, Cases Controls
country, ~ Comments
reference Sex Number Method of selection Number Method of selection

Borders, M. 526 Series of clinic patients with epithelioma 500 Series of clinic patients without epithe-

1920, F. W of the lip: lioma of the lip:

ULS.A. (43). Percent Percent
Tobacco users 80.5 Tobacco users .............. 78.6
Smokers Smokers
Cigarettes Cigarettes
Chewers Chewers ....
Pipes ..........., Pipes
Cigars... 2... ee eevee Cigars .......... :

Ebenius, M. 439 Clinic patients with cancer of the lip: 300 Not defined. t Estimate of prevalence
1943, F. 33 of use,
Sweden (87). Percent Percent

Male Female Male Female
Tobacco users - 19.7 —_— Tobacco users . 68.7 —_—
Tobacco users Tobacco users ........ — 1-2
(all pipes) oo 57.6 Pipes .......00..0.... 22.9
Pipes tee eeeeee 61.8 — Chew or use snuff ..... 60.7 —
Chew or use snuff .... 47.4 — Cigars and cigarettes .. 32.5 —_—
Cigars and cigarettes .. 12.9 —_

Levin et al., M. 143 Cancer Institute patients with cancer of 51 Cancer Institute patients with non-can-
1950, the lip: cer diseases of same site:

U.S.A. (169). Percent Percent
Smokers 2.0.0.0 ....00.0.000, 84.5 Smokers ...........0.0...., 74.0
Cigarettes 2.0.00... 0... ca 45.3 Cigarettes .........00.0...0.. 43.0
Pipes ....... 0.00 cece eee eee 48.1 Pipes ....... 0.0.0... ce eae 30.7
Cigars 2.0.0.0... eee 26.5 Cigars oo... eee eee 34.9

 
o9€

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, Cases Controls
country, Comments
reference Sex Number Method of selection Number Method of selection
Mills and Porter, M. 124 Deaths from cancer of oral cavity in Cin- 145 Sample of population of Columbus, Ohio,
1950, cinnati and Detroit, 1940-45 and 1942- in same proportion of color, sex, and
U.S.A. (186). 46 respectively: age as in cases:
Percent Percent
Cigarettes only ...........-.. 35.5 Cigarettes only ............. 32.4
Pipes, cigars, or Pipes, cigars, or
combinations - 54.8 combinations - 29.7
Moore et al., M. 112 Patients over 50 years old since 1951 with 38 Patients of same age groups with be-
1953, cancer of oral cavity: nign oral lesions or benign surgical
U.S.A. (198). conditions:
Percent Percent
Chewers oo... ccc cece ee eee 58.0 Chewers ...... eee eee cece 31.6
Pipes... 0... cece ee eee 42.0 Pipes .. 0... eee cee eee eee 47.4
Cigars and cigarettes seeeee 88.4 Cigars and cigarettes . 52.6
Sadowsky et al., M. 1,136 Hospital patients with lip, oral, and phar- 615 Patients with illness other than cancer:
1953, yngeal cancer, 1938-43: Percent
U.S.A. (282). Percent Cigarettes only . 63.3
Cigarettes only 42.3 Cigars only ..............05. 3.4
Cigarsonly  .... 02... cee eee 4.0 Pipes only .............0.002 7.0
Pipesonly .........-.0 ee eee 17.8 Mixed ....... 0.00 ccc ce eee ee 23.1
Mixed 2... . cece cece ee eee eee 28.2
Sanghvi et al., M. 657 Hospital patients with cancer of oral cavi- 288 Hospital patients with diseases other Smoking is of bidis among
1955, F. 81 ty and pharynx: 112 than cancer: both cases and controls.
India (2417). Percent Pereent
Male Female Male Female
Smoke andchew..... 38.8 3.7 Smoke and chew . 24.0 —_
Smoke only .......... 46.7 6.2 Smoke only .......... 50.0 6.3
Chew only ........... 11.7 64.2 Chew only ............ 8.7 23.2
Neither .............. 2.7 25.9 Neither 17.3 70.5

 
e9€

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, Cases Controls
country, - -— Comments
reference Sex Number Method of selection Number Method of selection
Ledermann, M. 240 Patients with cancer of oral cavity and 62 Patients with cancer of skin, bone, and Differences between cases
1955, pharynx: muscle: and controls for both
France (162). Percent Percent high and low alcohol in-
Nonsmokers ............ 4.6 Nonsmokers ................ 17.2 take are insignificant
>>20 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 ora) cavity: 207 Patients with cancer of other sites and
1957, F. 116 232 benign diseases:
U.S.A. (818). Percent Percent
Male Female Male Female
Nonsmokers 3 47 Nonsmokers 10 70
Cigars ............... 20 — Cigars 13 _
Pipes .............6.. 1t — Pipes 6 —
Mixed ............... 8 — Mixed 8 _
Chew ................ 17 — Chew ...... 8 _
Cigarettes 57 53 Cigarettes 63 30
>35 cigarettes >35 cigarettes
per day : 29 _— per day : 17 —
>16 cigarettes >16 cigarettes
perday ............ —_ 34 per day 11
Schwartz et al., M. 3382 Hospital patients with cancer of oral cav- 608 Hospital patients with non-cancer  ill-
1957, ity and pharynx: ness and accident cases, matched by
France (248). age:
Percent Percent
Nonsmokers 16.4 Nonsmokers .............4.. 23.4
Cigarettes only . 62.7 Cigarettes only . 58.2
weet eee eres esssuae 3.3 Pipes only .................. 3.0

Pipes only

 
v9E

TanLe 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, Cases Controls
country, - - Comments
reference Sex Number Method of selection Number Method of selection
Wynder et al., M. 178 Hospital clinic patients with cancer of 220 Patients in same clinics with non-malig-
1957, : F. 34 oral cavity and pharynx: . 214 nant conditions, matched by sex and
Cuba (825). age:
Percent Percent
Male Female Male Female
Nonsmokers ........- 4 24 Nonsmokers ......-..- 16 66
Cigarettes Cigarettes
predominantly ..... 45 62 predominantly ...... 45 27
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:
Percent Pércent
Cigarettes Cigarettes 2.0.0... ce eee eee 36
Cigars Cigars 2... ee ec ee eee 9
Pipes Pipes 2... cece e eee ences 16
Mixed Mixed 0.0... ccc cece eee cee ee 13
Peacock et al., M. 25 Hospital patients with oral cancer: 74 Patients in same hospital without oral
1960, F. 20 72 cancer and 117 male and 100 female
U.S.A. (210). out-patients, randomly selected.
Percent $2.6 percent of first group, and 43.3 per-
Chewed or used snuff over 20 eent of second group chewed or used
years (all patients) ........ 55.6 snuff over 20 years.
Staszewski, M. 383 Male patients with oral cancer: 912 Male patients with other cancerous and
1960, Percent non-cancerous conditions:
Poland (259). Nonsmokers ........-.00006- 5.7 Percent
“Heavy” smoking index 72.8 Nonsmokers ........+.000005 17.3
Cigarettes only 92.3 “Heavy” smoking index ..... 49.0
Pipes and/or cigars .......... 12.8 Cigarettes only ......0..065. 60.5
Pipes and/orcigars ........- 11.1

  
 
S9E

TABLE A28.—Outline of retrospective studies of tobacco use and cancer of the oral cavity (cont.)
(Data cbtained from patient interview and other sources)

 

 

 

 

Author,
year, Cases Controls
country, a Comments
reference Sex Number Method of selection Number Method of selection
Vogler et al., M. 188 Clinic patients with cancer of lip and oral 521 Patients of same clinic with other can- t Due to varying tabular
1962, F. 92 eavity: 1,064 cer or non-malignant conditions: treatment of data, per-
ULS.A. (298). Percent centages of tobacco
Male Female users are not all based
Chewers ............. $32.9 — Percent on the same number of
Excessive chewers .... 22.9 — Male Female cases.
Snuff dippers ........0 — 72.0 Snuff dippers ......... tee t6.1
Excessive snuff
dippers ............ _— 41.3
Tobacco users ........ 90.0 90.0 Tobacco users ........ 56.0 56.0
Vincent and M. 66 Successive patients with lesions of buccal 100 Successive patients attending gastroin- Male patients used con-
Marchetta, F. 16 eavity and oropharynx: 50 testinal clinic, age-matched: siderably more alcohol
1963, Percent than male controls.
ULS.A. (297). Oral Oro- Data refers to all forms
Males: Cavity pharynx Percent of smoking expressed
Nonsmokers ......... 3.0 — 27.0 as cigarette equivalents.
<20 cigarettes Cigarette equivalents:
perday ............ 18.8 15.1 24.0 l cigar = 5 cigarettes
>20 cigarettes lpipe = 2 cigarettes
perday ............ 78.7 84.9 49.0 t BN=Betel nut.
Females:
Nonsmokers ......... 55.5 28.6 82.0
<20 cigarettes
perday ............0— -— 8.0
>20 cigarettes
perday ............ 44.5 W104 10.0

 
99€

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, Cases Controls
country, Comments
reference Sex Number Method of selection Number Method of selection
Shanta and M. 552 Patients with oral and pharyngeal cancer 300 Controls residing in
Krishnamurthi, =F. 206 (unsure of confirmation) : 100 game area matched
1964, Percent for age, sex, and
India (256). Buccal Anterior Posterior class:
Males: Lip mucosa tongue tongue Pharynz Males
No tobacco habit ....- _— 2.0 1.2 2.0 5.3 39.1
Smokers ......--+-- 50.0 45.7 66.6 75.0 12.8 52.7
Number of cases (12) (293) (69) (48) (180) (300)
Females: Femalea
No tobacco habit .... 14.3 11.0 33.3 —_ 40.0 88.8
Smokers ......----- _ 4.7 5.5 _ 8.8 _
Number of cases .... (7) (152) (18) (4) (25) (100)
Wahi et al., M. 589 Patients with oral and pharyngeal car- 589 Patients matched for age, sex, religion,
1965, F. 232 cinoma: 232 and social class.
India (802). Percent Percent
Nonsmokers ....+ +--+ -- ee 0e+ 9.62 66.5
Smokers ....---. cess eer renee 17.05 21.2
Chewers (Betel nut) ....----+ 35.44 5.9
Both ....... 0 cc eee cee eee eens 37.88 6.4
Hirayama, M. 369 Patients with oral and pharyngeal carci- 277 Patients with other (unspecified) dis- Found only a suggestive
1966, F. 176 noma: 163 eases: association between
Central and Percent Percent alcohol-drinking and
South East Male Female Male Female ora) cancer in non-
Asia (124). Nonusers ....--2-0005 1.6 2.5 17.0 33.0 chewers only.
Smokers .....-..---+5 17.1 2.6 23.8 1.2 + BN-Betel nut.
Smokers, TBN and
tobacco chewers . 46.7 6.6 24.9 1.8

 
L£9€

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, Cazes Controls
country, Comments
reference Sex Number Method of selection Number Method of selection
Keller, M. 408 Patients with squamous cell carcinoma of 408 Next male patient admitted to same hos- Excessive alcohol con-
1967, oral cavity and oropharynx confirmed pital within 5 year age range. sumption noted for
U.S.A. (140). histologically. Three New York City VA cases involving floor,
Hospitals 1953-68: mesopharynx, and
Percent Percent tongue.
Nonuserg ................... 6.1 14.2 Findings indicate the
Cigarettes .........000.0...., 68.6 56.4(p<0.0001) association of heavy
Pipeonly ......... Se ceeeees 4.0 2.9 drinking with cancer
Cigaronly ..............00,. 6.9 6.1 independent of the
amount of tobacco used.
Martinez, M. Patients with epidermoid carcinoma of 345 115 male and 38 female hospita] or clinic Cases found to consume
1969, F, 38 oral cavity and pharynx: 14 patients without cancer; 330 male and more alcoholic bever-
Puerto Rico 76 female residents of same region, ages than controls.
(188). age and sex matched.
Percent Percent
Nonsmokers .....,.......... 13.7 19.2
Heavy tobacco users ......... 24.8 12.2 (p<0.0001)
Keller, M. 304 Patients with primary basal or squamous 304 Patients from same hospital matched for
1970, cell carcinoma of Jip: age and race.
U.S.A. (141). Percent Percent
Nonamokers ...... bee eevee 7.8 16.6 (p<0.001)
Cigarettes only ........... «+. 60.2 52.8
Pipeonly . 6.0 3.4
Pipe, other . 6.8 0.4 (p<0.01)

 

 
99e

TABLE A28a.—Summary of results of retrospective studies of smoking by type and oral cancer of detailed sites

 

Author
reference

 

Tobacco
chewing

Betel nut

chewing Miscellaneous

 

Broders (48).......Li

 

Ebenius (87). 2.0.0.0... ce eee eee

 

 

 

Mills and
Porter (186)

ce bcd kk ube ben ene nee eee EEE eRe bee Edn een EEE ee eR AEE EOE REE EEE Ee Ee Fee ee eee nee wee eveueeeeesss.-Pipes and cigars

combined—oral

(+).

 

Moore et al. (193)

Lip,
mouth (+)

bese see ae sees Snuff—iip,

mouth (+).

 

Sadowsky
etal. (232)

pharynx (—).....

Cigarettes Pipes
and cigars Bidis only
cece e ee wee eet eee ete ee teens Lip (4). 2.2... 65 cece eee eee
Lip (—). ce. cc ee eee eee Lip (4). 0.000006 wee eee cee eee
Se ee een et ee eee ee Lip (4A) cee cee ene
Lip, see eee Lip,
mouth (—). mouth (—)
cen ee ee eter eee ene Lip, tongue,

other oral (-+)

 

Sanghvi et al.
(241)

cece nee eens If smokers and

chewers—base
of tongue,
hypopharynx
(+).

 

Lederman (162)...

 

Wynder et al.
(313)

Female (+)....

. Gingiva,
lip (*).....

 

Schwartz et al.
(248)

we ee Oral (PB) occ cece ee ce eet ee ete tence teenies
ce eet e et ae eee ene ttee Each site
except
tongue (+)....
Pharynx (+). ......6-.. Oral (—) 2. ce ccc ee ee tees

 
69€£

 

 

TABLE A28a.— Summary of results of retrospective studies of smoking by type and oral cancer of detailed sites (cont.)

 

 

 

 

 

 

— - -— _ - pe
Author Cigarettes Pipes Pipes and Cigars Tobacco Betel nut .
reference Cigarettes and cigars Bidis only other forms only chewing chewing Miscellaneous
Wynder et al. a Oraland ec cce cece ee eee
(825) pharynx, pharynx,
Male (—) Male (+),
Female (-++) Female (+)
Wynder et al. Pharymx (+), eee cece cee ccevinetrsrreeveeerepee, Tongue, eee eee cece eee Pipes and cigars
(322) other sites (—). gingiva, combined—
pharynx (+), tongue (+).

 

Peacock et al.
(210)

Staszewski (259)..

 

Vogler et al.
(298)

 

Vincent and
Marchetta
(297)

Shanta and
Krishnamurthi

(256

 

STAD OPAL ee ttt trrren vtttetrnn tien nin rn TT
cavity (-+).....

 

 

 

 

Oral (TY eee... Snuff—oral (-4)1

 

Pipes and cigars
combined—lip,
oral cavity (*).

 

-eAll forms com-
bined (+),
Female (+)
Snuff—lip and
buceal cavity in
hoth cases.

TO elec tet er tvntene ley All forms
combined—

oral (+),

pharynx (+).

 

 

 

Bee eee cence ree Cesc ve eee eeeee, Lip, All smoking types
buccal —pharynx (+),
mucosa (+).. post tongue

(+).

All forms com-
bined—lip, oral
cavity, pharynx

(+).
Ooze

TABLE A28a.—Summary of results of retrospective studies of smoking by type and oral cancer of detailed sites (cont.)

Author Cigarettes Pipes Pipes and Cigars Tobacco Betel nut
reference Cigarettes and cigars Bidis only other forms only chewing chewing Miscellaneous

Wahi et al. Anterior ec cee en enn e beet ae Cb be ebb c ccc an ene nent atnbnnnee Anterior All forms com-
(802) tongue and tongue and bined—all
buccal buceal sites (+).
mucosa, mucosa,
Males (+) Males (+)

Hirayama (124)... 0.00. ee cece tee eee eee eee AN sites (—) occ cece ace Allsites (—)... Allsites (—)................. All forms com-
bined—base of
tongue (+),
oropharynx (++).

Smoking only
combined
—buccal
mucosa (+).

Keller (140)....... Allsites (4) 0.000 (0c cee cee cee eee Allsites (—). 0... ccc ce eee eee Allsites (—-) 0... eee ee cee eee All types smoking

combined, heavy
—floor of
mouth and
tongue (+).
Martinez (183).....Oral cavity,

Pe ee Ee ee Cente ee EEE EE CCE E ERD EEE Ue eee bee nnn s ues ee ete eeeeeereeeeaaetecenee All types of
pharynx (-+-) smoking, heavy,

eombined—oral
cavity (+),
pharynx (+).

Keller (447) ....... Lip (—) occ ec enn cee eee ee eee teen necenes Trip (4+)... Lip (—). 00. cece ce cece eee enee All types of

smoking com-
bined—lip (+).
' Only in individuals of low economic status and over 60 years old.
Symbols: (+) = significant association.
(—) = association absent or not significant.
(*) 2 association of doubtful significance.
Ze

TABLE A29.—Experimental studies concerning oral carcinogenesis

 

 

 

 

 

 

 

 

Author, A. Method.

year, Animal B. Frequency and/
country, and or duration. Results
reference strain C. Material.

Kreshover, 78 Swiss and A. Painting of lower No macroscopic or microscopic changes in controls or experimental animals.
1952, C57 mice. lip mucocutaneous
U.S.A. region.

(152). B. 10 times in 76 days.
C. Cigarette smoke
‘concentrate’.

Salley, 36 Syrian A. Painting of cheek Number of Number with ‘Number with
1954, hamsters. pouch. Treatment: survivors benign tumors carcinoma
U.S.A. B. 3 per week for 16 Acetone solvent 5 1 2
(238). weeks. Benzene solvent 4 — —-

C. Benz(a) pyrene in
acetone or benzene.

Holsti and 60 Albino mice A. Painting of lips No oral or labial changes seen in controls or experimental animals.

Ermala, (40 controls). and oral cavity.
1955, B. 140 times in 12
Finland months.

(190). C. Tobacco “‘tar”’.

Moore and 80 Syrian A. Material soaked onto Inflammation
Miller, Golden hamsters. wad and secured Original Surviving Number and basal cell
1958, in cheek pouch. Treatment: number over 1 year tumors hyperplasia
U.S.A. B. Wads replaced 8 Controls oo... ee eee ee 30 23 we 4
(192). times in 2 years. Smoke condensate 80 55 we 32

C. Smoke condensate Benz (a) pyrene 20 16 .s 9
Benz (a) pyrene.

Guerin, Strain IC and A. Chamber inhalation Original Buccal
1959, strain W rat. of tobacco smoke. number Survivora tumors
France B. Daily (2). Controls .........5-- 40 39 0/39
(108). C. Up to 5% months. Experimental ....... 100 68 5/68 (3/6 definite

epithelioma)
ZLE

TABLE A29.—KHxperimental studies concerning oral carcinogenesis (cont.)

 

 

 

 

 

Author, A. Method.

year, Animal B. Frequency and/
country, and or duration. Results
reference strain C. Material.

Peacock et al., 124 Syrian A. Packing of cheek No tumors noted in any of the 42 animals surviving over 1 year.

1960, Golden hamsters. pouch,

U-S.A. B. 1 year.

(210). Cc. Snuff, Tobacco,
Bland material.

Dunham and Syrian Golden A. Packing of cheek Hyperplasia Malignant
Herrold, hamsters. pouch. Original and/or in- pouch
1962, B. Normal lifespan or Treatment: number Survivors flammation tumore
U.S.A. 5-30 months. Betel quid Pies vee eres waa 375 90% over Ll year 19 —
(84). C. Betel quid ingredients DMBAand MCA ............. 71 56/71 over 5-30 months — 23/56

7-12 dimethylbenz(a)-
anthracene (DMBA),

 

 

 
 
  

Methylcholanthrene
(MCA) in beeswax
pellets.
Moore and Albino hamster A. Painting oral mucosa. Animals with
Christo- exteriorized B. 3 per week for 683 Treatment: lesions (time)
pherson, oral pouch, days. Controls... ec ce teen cece ee neeee Q-18 (at 392 days).
1962, C. Cigarette smoke Smoke condensate .....0..0... 000 ce cece cee eves 0/20 (at 387 days) (10 showed hyper-
U.S.A. condensate. keratosis).
(191), DMBA in 0.50% DMBA 200. cc cen ee cee cee teese pens 14/21 microscopic cancers (at 90 days)
petrolatum. (invasive squamous cancer originating
in the skin at the edge of the pouch).
Salley, CAF, strain A. Ultraviolet light Treatment: Number Duration Tumors
1963, mice. exposure to and Ultraviolet light and weeks
U.S.A. painting of lips. cigarette smoke .................... 40 94 —
(289). B. 3 per week for 98 B(a)P and UV light ......0.0.0....... 40 48 —
weeks, UV light ...... oe 40 94 —_
C. B(a)P in acetone Bla)P wool cee ee 40 45 —_

Cigarette smoke
UV light.
74

TABLE A29.—Experimental studies concerning

oral carcinogenesis (cont.)

 

 

 

 

 

Author, A. Method.
year, Animal B. Frequency and/
country, and or duration. Results
reference strain C. Material.
Hamsters A. Application to Original
cheek pouch. Treatment: Number Survivors Duration Lesions
B. See results. Cigarettes 5 per week vee 70 5B 64 —
C. See results. DMBA once .................. 13 6 128 2 hyperplasia
Croton oi! 8 per week . 10 10 30 _
DMBA once and cigarettes
5 per week ........0........ 30 28 81 12 hyperplasia
4 dyskeratosis
1 carcinoma
DMBA once then croton oil
5 per week ..............,.. 29 27 81 7 hyperplasia
6 dyskeratosis
3 carcinoma
Bock et al., ICR Swiss A. Painting mouse Number tumors/
1964, mice. skin. number mice
U.S.A. B. See results 36 weeks. Tobacco equivalent with tumors
(30). C. Various extracts of Treatment: (cigarettes/daily) (amall papillomas)

 

unburned tobacco
DMBA.

DMBA once then:
Acetone benzene extract ....

Concentrated Ba(OH), extract .......

Diluted Ba(OH), extract... . eee eee
DMBA only ........,.......

Acetone benzene extract ..................

Concentracted Ba(OH) 2 extract
Diluted Ba(OH) 2 extract ...0....00...00..0 0000000.
None ......0.....0.00.0.0..0¢ Ce eee eee

 

 

2.5
0.5
0.5
2.5
0.5
0.5

16/7
18/8
6/2
ve

TABLE A29.—Experimental studies concerning oral carcinogenesis (cont.)

 

 

 

 

 

Author, A. Method.
year, Animal B. Frequency and/

country, and or duration. Results

reference strain C. Material.

Protzel et al., Swiss Webster mice A. Swabbing of labial Original Percent at 18 months with
1964, with some having mucosa. number Papillomas Cancer
ULS.A. liver damage in- B. Up to 13 months. Alcohol and ccl, treated .............. 40 74 46
(213). duced either by C. B(a)P in acetone. Alcohol treated ............0.000000005 40 84 50

CC14 or ethyl cc, treated 2.0... .. cece eee 40 90 40
alcohol. No toxin ......... cece ee ee cee 40 42 15

Reddy and Swiss female A. Intravaginal Original
Anguli, mice. instillation. number Survivors Lesions
1967, B. Daily for 324~380 60 40 3/40 raised papillomatous
India days. malignant growths
(219), C. “Pan” mixture of 4/40 possible carcinoma-

areca nuts, lime, in situ,
and chewing
tobacco.

Elzay, Syrian Golden A. Application to Percent Percent
1969, hamsters. cheek pouch. Original Mortality Number with with
U.S.A. B. Daily for 200 days. Treatment: number rate animals tumors cancer
(90). C. See results. DMBA Alcohol Smoke 29 41.0 17 100.0 50.0

DMBA Aleohol ........ 29 66.0 10 60.0 40.0

DMBA sees Smoke 29 42.0 14 100.0 70.0

DMBA oo ........ eee ee 29 48.0 16 100.0 38.0

Alcohol Smoke 29 42.0 14 — _

Smoke 29 42.0 14 — —

 
SLE

TABLE A31.—Summary of methods used in retrospectvie studies of tobacco use and cancer of the esophagus

 

 

 

 

 

 

Author,
year, Cases Controls
country,
reference Sex Number Method of selection Number Method of selection Collection of data

Sadowsky et al., M, 104 White patients admitted during 1938-43 to 615 White patients with illnesses other than Obtained by 4 specially
1953, selected hospitals in New York City, cancer admitted to same group of hos- trained lay interviewers.
U.S.A. (282). Missouri, New Orleans, and Chicago. pitals during same period. 242 records out of a total

of 2,847 excluded be-
cause of incomplete or
questionable smoking
histories.

Sanghvi et al., M. 93 Consecutive clinic admissions to Tata me- 288 Consecutive clinic admissions of patients By means of ‘‘detailed
1955, morial Hospital, Bombay. without cancer. questionary.”” No other
India (241). 107 Consecutive admissions of patients with details given.

eancers other than intraoral or eso-
phagus.

Wynder et al., M. 39 Patients admitted to Radiumhemmet, 115 Patients admitted to same hospital with
1957, F. 35 Stockholm, during 1952-55. 156 cancer of skin, head and neck region
Sweden ($22). other than squamous cell cancer, leu-

kemia, colon, and other sites. No
matching.

Staszewski, M. 24 Patients admitted to Oncological Institute 912 Other patients sent to Institute with No details given on
1960, during 1957-59. symptoms probably not etiologically method of data collec-

Poland (260).

connected either with smoking or with
diseases of esophagus, stomach or du-
odenum.

tion. No age adjust-
ment or matching. Av-
erage age of cancer
patients, 60.5; controls,
53.