Document ppxN2dQn0LEaQKbbmbNe1pQ47
FILE NAME: Smoking (SMOK) DATE: 1954
DOC#: SMOK004
DOCUMENT DESCRIPTION: Journal Article - Etiology of Lung Cancer - Present Status
Etiology of Lung Cancer: Present Status
M O R T O N K. L K V I N , M . D . , A L B A N Y , N K W Y O R K
(Asmhtnnt Com mixoioner for ,1 /alien! Storing, AVie York Shite Drparimt 11/ of Health)
!i { VAiLAiiMv evidence points to a number of lx . different possible etiologie factors for hinp; nincer in man. These include chemicals, radia tions, dust or fumes encountered by workers in various occupations, and cigaret smoking. Inlastries and occupations with evidence of abnor mally high lung cancer risks are chromate prolurticm; production of illuminating gas (studied in Kngland); 1 lining of uranium ores in Solineelerg, Germany, and Jaehymov, Czechoslovakia; nickel refining in South Wales; asbestos manu-1
. rVluring in Kngland; and metal grinding in! ; kngland.1 Recent evidence points also to inl erased lung cancer among welders and other f wickers exposed to metal fumes or dust in the ; United States.5 Suggestive evidence regarding
.wral other occupations has been reported, and it seems probable th a t other as yet unknown oc! rapatinns with high lung cancer risks remain to be 1 'liseovered.
Evidence for relationship of these oecii])a,tions 1 In lung cancer consists chiefly of the increased
mortality rate from lung cancer observed among makers in these occupations. Exact, risks have i Icon estimated for two of these occupations, j diromate production (in the United States) and I illuminatinggt.smanufacture (in Kngland.)1 For ; :>few there is also experimental evidence of a ' mrcinogenic agent in the material to which 1 workers arc exposed, but in no instance has lung ancer been produced in animals by such ma| Serial. In the case of the (diromate industry, in | which lung cancer mortality has been shown'to | ie 14 times that of the United States population I *inong white workers and SO times among Negro workers, application or injection into j animals of vai ious materials to which workers are ripost'd has thus far failed to produce malignant
.`'I'biics rnportc:) Jicrr were a i d e d b y a g r a n t f r o m th e National C a n c e r I n s t i t u t e , U.S. P u b l i c H e a l th Se rv ic e COS KiO). and f oin th e N e w York S t a t e D iv isi on , A n ier ie an fsnccr Society.
lung tumors. .Nevertheless, tlicrc is little or no disagreement, as to the existence of a. lung cancer etiologie agent in the (diromate industry'.
A relationship between lung cancer and tobacco smoking lias been suspected for many years. Sta tistical studies, of which the first apparently was that of Muller' in 1939, have uniformly shown a, higher percentage of cigaret smokers among lung cancer eases than among control groups. In the past few years this relationship has received increasing public notice so that it is today widely debated and discussed in the news papers, in national magazines, and, no doubt, by the public itself. Many physicians, statisticians, and others engaged in cancer research have ex pressed themselves in the public press as to the significance of the reported studies on this as sociation. Considerable difference of opinion and of emphasis lias thus been elicited. Appraisal of 1bo nature of the evidence regarding tobacco as a possible etiologie factor in lung cancer lias thus become of increasing importance, because of the widespread public interest in and concern over the subject, the large financial and tax interests at slake, and, most important, the steadily rising mortality from lung cancer reported each year. .It is, therefore, necessary that physicians and public health authorities appraise the situation as it now exists to determine what conclusions may be drawn and what action may be required.
Most studies regarding smoking and lung can cer thus far ma.de--18 are listed in a recent, arti cle1---have compared the smoking histories of lung cancer patients with those obtained from other persons, usually' patients with other diseases in the same hospital. Almost without exception, these studies have found more cigaret smokers among lung cancer patients than among other patients. If these observations arc valid, it would mean that, lung cancer occurs more fre quently among cigaret smokers than among nonsmokers.
Mnrdi Ifi, 1954
76!)
MORTON L. L E V I N
Severn,1objections can be raised to this type of study, and these objections must be carefully weighed to determine what, possibilities of error east, in such studies, whether these are sufficient to invalidate the conclusions reached, and what, bearing the evidence has on the question of smok ing ns a cause of lung cancer.
The first question which arises with respect to these studies is w hither they prove that a real association exists between smoking and lung cancer. In other words, do the studies prove that persons who smoke cigarets develop lung cancer more frequently than do those who have nevei' or rarely smoked, for this is the meaning of "association" as used with respect, to this type of evidence. "Association" does not mean, a,s lias been implied by some writers in the press, merely that the rise in lung cancer mortality has ac companied the rise in the use of cigarets. The guilt, attributed to cigarets is not based on this latter type of association. The concomitant rise of lung cancer and cigaret consumption would be expected to follow a true association between tire two, but by itself cannot be con sidered as more than suggestive evidence of it. The evidence which is at hand is th at cigaret smoking is more frequent and hea vier among per sons who develop lung cancer than among those who do not.
The fact that many studies by independent, in vestigators in this country and abroad show the same result is accepted by all or most authorities as proof that some association exists, i.e., that cigaret smokers do experience a higher incidence of lung cancer than do nonsmokers. It may lie of interest,, however, to consider why there should he any doubt at all on this point.
Two possible sources of error must, be consid ered, those due to bias in obtaining the history and those due to bias in sampling. Whore the smoking history is taken as part of a special investigation, one must, consider whether the in terviewer, by reason of his own bias or conviction, influences the patient in the, answers the latter gives. In at least two studies the clement of in terviewer bias would seem to have been eliminated if it existed. Doll and Hill considered that they had demonstrated this error did not exist in their study since in .TTi patients believed to have bronchial carcinoma at the time of interview, but shown later not to have the disease, "the smok ing habits of the wrongly diagnosed group were sharpl}' distinguished from the habits of the cor
--n
rectly diagnosed groups and were statistics: | indistinguishable from those of all the otb* ; patients suffering with other disease." 1 In tb 3 Roswell Park Memorial Institute studies,6,6b w i in 1938, we consider this source of error to lim lieen eliminated, first, because the studies nn ;
undertaken in the belief that no association real!) I existed and, second, because of the fact that lb ! smoking histories were not part of a separate i> ' terview but were obtained as part of the routir,' :
history taken on admission before any diagnose had been made.
A second possible source of error which Ln ! been pointed out is th at one could not, be, ccrl.v * that the lung cancer cases studied were represent, l
tivc of ail lung cancer cases or th at the conk" i
patients were representative of the general popub- j; tion. However, those two conditions are n-'i :
necessary for a valid study of the association < ; two variables. First of all, the cases and contrim ]
need not come from the general population In;' ;
from the same population, i.e., the contrrt j
should he persons of the type most likely' to ent<" :
the stud}' as cases. Second, tire cases and con- :
trots need be representative only with respect b
the factors studied, in this instance smokier ;
history.
,
The theoretic sampling questions raised aW with respect to the case studies may thus be sum- ; inarized in tire following questions:
L How likely is it that the control and lumr, cancer cases in the studies reported were draw: i
from two different populations which differe;!
significantly with respect, to smoking and differs I
always so th at the control cases came from t, | lighteivsmoking population than the lung canm 1 rases/O
2. flow likely is it that these sampling bins* ;
would be more marked for cigaret smokers tins ' for pipe and cigar smokers and more marked (a I heavy cigaret smokers than for light eigareb smokers?
3. flow likely is it, that lung cancer cases wh smoke are more apt to go to the hospital or that;
patients with other diseases who smoke are lea
apt to do so?
j
4. How like)}' is it th at these sampling bia.w :
should occur repeatedly in studies made in dif
ferent countries and in different sections of lb 1 same country?
Xone of these contingencies seems very likeli and their occurrence to so marked a degree urt
show the differences between smokers and m
ETIOLOGY OF LUNG CANCER: PR E VE NT ST AT UE
VS|U,F, I.-- E rtimatkd P rf.valf nof , Ha t k h 11 of L unvj C amckr fku 100,000 M aofs of Rkmcotfd A gf s a .vd Va r i o u s C i o akkt S m o k i n g H i r t o h i f G'
-Xu tu b e r - - --Dung Cancer Control
Estimated Prevalence Hates
^ - Q u a n t i t y S m o k e d D a i l y 7'
All
Quo.nti-
Heavy''
ties
.Gone
Relative Prevail eneo'f--'
All Quo.ntiI ion vy ties
Putionfs ag ed .50 to 5b y e a r s Doll arid HUH Wynder and G r a h a m 2 Sndowskv, Gilliam, a nd C ornfie ld 2 Rreslow, Ho aglin, R a s m u s s e n , a n d Roswell Bark M e m o r i a l I n s t i t u t e
I'fOients a g e d 0.) a n d 69 y e a rs Doll an d H i l l 2 Wynder and 'Graham2 Sadowskv, Gilliam, and Cornfield2 Hreslow, Ilo ag lin , R a s m u s s e n , a n d Roswell P a r k M e m o r i a l I n s t i t u t e
Abrams2 Abrams2
276
275
91
42
7
12
(3
2.58
21 0
117
47
4
27
1 1
198
208
87
4 1
12
7
4
212
212
102
4 6
17
7
172
657
141
109
15
9
7
197
199
127
62
0
187
160
128
70
5
29
15
76
71
4 t
7 l
.5
9
4
168
169
422
78
17
25
5
197
675
479
280
50
9
5
* Estimated ac co r d in g t o t h e m e t h o d of C o r n f ie ld .>> *> All d at a a p p c t r i n g in th i s ta b le , ex c e p t for Ros we ll P a r k M e m o r i a l I n s t i t u t e figures, a r e t a k e n fr o m th e p a p e r b y Bres-
`uw<1nl?
<Quantity s m o k e d dai ly, ex c e p t fo r t h e p r e s e n t s t u d y , is all f o r m s of s m o k i n g ex p res se d as r i g a r e t s with pipe s a n d cig ars m,averted to tho.ii e q u i v a l e n t s in cigavots as follows:
Dull and Hill--- 1 ou n ce t o b a c c o = 4 e i g a r e ts a d a y \Yynder a n d Gj a h a m -1 ci gar 5 eiga r e t s ; ! p ip e fu l 2 ' / ? ei gar et s Sndowsky, Gilbr.m, a n d C o r n f ie ld - I ci g ar ~ 10 ei g ar et s ; 1 o u n c e p ip e to b a c c o = 20 ei g ar et s I'm the Bicslow c nl. s t u d y q u a n t i t y s m o k e d da il y in cl ude s o n ly cigaret. sm o k in g . 4 Relative pr ev al en ce ar e the. following ratio s: h e a v y -- rfitn ai m in g h e a v y s m o k e r s / r a t n a m o n g n o n s m o k e rs ; all q u a n t i t i e s rate among sin :k e rs/ ra te am o n g nonsm okers. * Heavy smokin g is defined as th e folio wing n u m b e r of e ig a r e ts or eq u i v a le n t s of cigaro.t.s per d a y : Doll a n d Hill, 50 or m o r e ; Wynder a n d G r a h a m , 25 or mo re ; S a d o w s k y , G ill ia m , a n d Cor nf ie ld, 41 or m o r e ; B r cs lo w et n l 40 o r m o r e ; p r es en t s t u d y ,
70 or more.
`mokers elicit xl hv the various studies is oven >sa likely. Their likelihood is probably least in `tinlies ma.de n hospitals, such as those at Rosvcll Park Memorial Institute,5 in which all pa tients arc admitted without- charge, and in the British studies of Moil and Ilill, made in patients in hospitals coming within the National Health Insurance scheme. Wynder and Cornfield's `Imly7 made of smoking histories of physicians sho died of lung cancer also is not subject to the possible bias of hospitalized eases.
The fact that 13 separate studies have shown the same result is strong presumptive evidence (hat an association exists between eigarot smok ingand lung cancer, i.e., that lung cancer occurs more frequonily among cigaret, smokers than among nonsmokers. Indeed, one may predict lli.it the "pros' >eetive" studies now under way will fully confirm the fact of a substantially increased risk of lung cancer among cigaret smokers. How ever, they should provide more precise estimates of the magnitude of this risk.
Magnitude o f In crea sed R isk o f Rung Cancer A m o n g C ig a ret S m o k e rs
Estimates of the extent of increased risk to
lung cancer suffered by cigaret smokers vary markedly. Table I, taken in part from the paper by Brcslow el a l.2indicates that in the age groups fifty to fifty-nine and sixty to sixty-nine years, male smokers have lung cancer prevalence rates from four to 15 times as great as among nonsmokers. Among "heavy" smokers, according to varying definitions, the relative prevalence is estimated a t seven to 29 times that of nonsmokers.
Tabic IIA presents estimated rates based on a tabulation of smoking histories 'of patients ad mitted t.o Roswell Bark Memorial Institute from 1938 to the present. These data, indicate that cigaret smokers have at least six times the risk of lung cancer incurred by nonsmokers. The ex cess risk among pipe and cigar smokers is much less.
In 'fable III A these data, have been recal culated, after adjusting the place of residence, classified into nine population density categories, of the noncancer cases to th at of the lung cancer cases. The indicated relative prevalence among smokers is not significantly altered by this adjust ment. The relative incidence ratios between smokers and nonsmokers arc based on the as sumption that the differences in smoking history between lung cancer patients and noncancer
March 15, 195
771
MORTON L. L KYI X
TARTK U
A . T s t i m a t i ' d A \ \ i : \ i , I Nc r Di TNCi : o n H u n k ; ( ' a \ r: i ; u i>i-;u 10 0 , 0 0 0 I'o i t i .a n n . v A m o m i P i i t ;, O k : a h , a n d O k ; a u k t Rmdmc a n d N o n mm n k k u s ( M a i , k s )
Age ( !n>up ( Yeans)
Yonsmokery
A nn u ;il Cigarot Smokers
1n c i d e n e e ............. Pipe
Smokers
-% ( 'igar Smokers
35 to 44 4.) to 54 55 to 04 55 to 74 75a m i o v e r
1.2
10.2
0. 3
04.8
15. 0
11.3
28.5
100.2
20.4 50.0
55.1
343.5
70.0
40.8
If). 9
302.1
71.8
01 .4
" T h e r e w e r e n o 1u n g c a n c e r e a s e s a m o n g p i p e a n d ei g a r s m o k e r s in t h i s a g e g r o i n
P>. XTi m h k k o r ( 1AS IPS
R a tio of Inridotirp
.1 t o N o i i s m o k r i s A m o n g
( 'igfiret,
Pipe
Cimr
Smokers
S m o k e rs Smokre (
8. 5
" ;j
7.0
l .0
1.2 f
0.0
0.0
l.H `t
0 2
1.4
of r
23.2
4 .2
5.4
ij
Age ('.roup ( Years)
35 to 44 45 to 54 55 to 01 55 to 74 75 a n d o v e r
' - - N o n s m o k e r s --.
Tung
Non-
( 'ivnce.v
rnnrer
1
5!
r>
122
Hi
18(1
13
HiS
1
80
37
0t 3
-Pipe" Smokers-
Tun;g
N'on-
('am "v
ranee r
1 1
2,
37
0
75
10
05
2
41
21
250
" Includes "p u re '' pipe an d eigar sm okers only. h In clu d e s c ig aret s m o k e rs w h o also s m o k e d p ip e s a n d /o r cig ars.
.-C gar" Tung
Cancer
2 8 5 2 17
S m okers-- N'onearner
10 34 52 71 32
205
--- ( 'ig a re t/' Tung
Cancer
30 T 00 182 72
7 400
Rinoki'i*1- fi Xoti riuiccj
iHi i air ;
301 j. 151 j 2d p
m) i
i ;j
TABIT) HI
A10. 0.0I0']0ST
IM AT Kl> P opula
t
TlfNfi ion A
( ' AN' CKK most; M a
ANNUAL ll C igar
k
fNriDhN'f'r: t S m o k k u .h
PKU and
X o x s m o k KKS
Age. C r o u p (Years)
X c w Y o rk S u ite"- --
Non-
AH
smokers Smokers Males
R a t io of Inoi-
d c n i'e Smokers
Nonsmokers
30 to 30 40 to 40 50 to 50 00 to 00 70 to 70
0.8 4.2 M .8 50.3 33.0
2.0 25.4 108.0 280.4 435.8
2.3 18.2 70.7 12 5 . 7 124.5
3.0 0.0 7.2, 5.0 13.0
" R ates h ised on incidence rates for lung ameer in New Y o r k S l a t e , exc lus ive of N e w Y o k C i t y , for 1010 -1051.
proximate true differences in the relative ri.4O
developing lung cancer. These data (Tiitt
I.VC) indicate that among males aged thirty yevd
and over who are light smokers (less than tdi
oigarets a day) the lung cancer risk is aby
doubled, in smokers of five to 19 cigarets a A r
the risk is about six times its great, and in tl.nj.
smoking 20 or more cigarets, approximately c)
times as great a,s in nonsmokers.
t
In Table V is presented a- further analysis ofv)
smoking history of male lung cancer patient*h'
.11oswell Park Memorial Institute, compared *i!
patients admitted with a presumptive diagim.j
A ge ( Y e a rs)
30 t o 30 40 t o 40 50 t o 50 00 t o 00 70 t o 70
P.
X o n sin o k ers- -
hung
N on-
C ancer eaneer
1
38
3
80
8
1 50
23
200
4
150
30
030
---(O g a r e t Tung
C ancer
Sm okers---N one iin e e r
10
170
57
244
152
300
140
225
25
72
300
1,077
/-. . . . . . . . . . . O t h e r . . . . . . . . . i
D in g
Non- s
C a n c e r C A I l C K ij
!
30 if
;$
c ,J
13
i w .li
25
244 r
10
1M il
52
fitf if
patients reflect similar differences between lung cancer patients and the population from which they come. Since there is no reason to believe that the smoking habit per so influences admis sion to the hospital, these ratios probably ap-
of lung cancer but whose symptoms upon fs! diagnosis were not due to the presence of fed rancor or any lung tumor. This is a severe ten1; the difference as to smoking history between cancer and other patients since smoking per*):
ETIOLOGY OF JXJXG CAXCEP: PII ESE X T FT A T (IS
TA K l.K IV A, E stimatku''- A n n u a i, L i n o O anouu I nt iok nck i'l'.ii ] 00,00 0 A monu M ai.us, C ic ak kt S mo k fu s and V on hm ok kii s , hv
Av K iu ii n A mo unt S m ok fu D aidv ( N kw Voihc S ta ti A)
Age ( Years)
::n t<> oo
dt) t o -`9 50 to : 0
fit) t o oo
70 t o : o 80 7 to '.u
Less th an
I ,S
8.0 88.2 59. I 82.2 20.8
5I >;t i I y
5 C i g a r e t s S m o k e d t o HI 1. 7 18.8 8 S O . 212.5 d 75. 0 02.7 '
20 or m o r e 8. -1 8t . 7
111.1 '17').0 005.-1 102.0
,Nn n s l o o k e r s
0.8 l 2 11.8 50.8 88. 0 15. 0
All S m o k e
2. 0 25. 1 10S 0 280.4 485.8 180.0
" For the m e diod of ca lc ula ting incidence rat.es, see Cornfield.8 h Based on re p o r te d l u n g c a n c e r in c id en ce fo r N ew Y o r k Sta te (exelusi ve of N'nw Y o r k ( A t y ) for HI 10 -19A1. f A dj us te d (n p o p u l a t i o n , male's ag e d M0 t o 70 y e a rs , N e w Y or k S t a t e , ex c lu siv e of N e w Y o r k C i t y , 1050 ce nsu s.
P . Pi-:ii C u n t 1) i s t k i n u t i o n '1 o f
S m o k f u s i n D at um .\' u m i i i : h o f ( ' i o a i u x s S m o k o d ''
Age (Years)
50 to 80 40to 40 50to 50 (>0to 00 70to 70
<--- - bo ss t h a n 5- -
Non-
bung
cancer
( 'a ticer
2.71 5.50 3.50 1.50 0.83 2.00 5.80 2.50 4.21 2.78
10 - - D a i l y X u i n b e r of C i g a r e t s
> to
.......... -
Non-
bung
cancer
( 'ancer
28. 10 23.00 20.05 ] 5. 81. 0. 54
10.07 57. 14 53.80 3.3.07 30.50
n A d ju s te d t< pla ce of res id e n ce of t h e lu ng c a n c e r g ro u p , &Pipe a n d ei ?ar sm okers n o t shown in this table.
- - 20 or M o r e
Non-
bung
cancer
( 'a nrer
40.01 37.34 20. 55 12.10 0.84
On. 07 71 .43 50.28 40. 15 33.31
Nonsmokers -
Non-
Tmng
cancer
Cancer
!5. 08
5. 50
20.00 4.70
22.41
4.02
20.00 11.08
37.58 10.20
C. CoM l'AUISON OF ESTIMATUI) PuhATlVK IxciDKN'CF f)F L t : \ ( ; C woick A mon' o C ioauut S mokkus and X onhmok kks
Age jYea rs )
80 to 30 40 to 40 `0 to 5!) M) to 00 70 to 70 80 t o 79"
5 5 10 20 ........................... D a i l y C i g a r e t s S m o k e d -
Ijess tb a n
to
or More
0. 0
2. i
4. 4
1. 0
3.3
8. 5
2.2
5. 8
8. 5
1.2
4 .2
8.0
2.4
14. 1
18.0
1 .8
0. 2
10.8
All Q u a n titie s
3. 0 0.0 7.3 5. 0 13.0 7. 2
n .Relative in c id en ce ( s m o k e r s /t io ti s m o k e r s ) o b t a i n e d a l t e r a d j u s t i n g a 11 ra t e s to t h e n ud e p o p u l a t i o n , N ew Y o r k S t a t e , ex clusive of N ew York City, 1050 census.
T A B L E V.-- ( moakf.t S mok uks A mono P ati k.vth w it h Lit no C anouu and w i t h O tii ioh D i smasks of t h k R ung ( Mo n t i ; mpits') in M aukh ( K dhwiim, P ark. M kmokjal I n s t i t u t k )
.On (Yean
------- - b u n g ( 'a n c e r ...... - -
Cigai -ot 'Smokers
( hises"
Number
Per (lent.
b u n g X o n t u m o r s /' -- - -
Cigaret Smokers
( discs
Number Per Cent
1udic uted Relative Ineidenee Smokers to All Others''
85 to 44 45 to 5 1 55 to 04 05 to 74 75 a n d o -or
81
30
00.8
120
100
00.8
218
182
83.5
no
72
05.5
14
7
50.0
17
11
01.7
37
28
75.7
40
20
50.5
17
4
23.5
1
0
0
10.5 3.5 3.0 0.2
403
4 00
118
00
I nc l ud es 18 cases with h i s t o r y of c'o m b i n a ti on p ip e a n d ci gar s m o k in g , n o t t a b u l a t e d in 'I'ab l e I IB . '' Incl ude s ch ro n ic b r o n c h i ti s , b r o n c h i e c ta s i s , e m p h y s e m a , a n d o t h e r d ia gn ose s. r Comparison here is between eigaret smokers and " all o th e rs" including nonsmokers a n d pipe and cigar smokers.
known to cause in some individuals chronic in- The differences in per cent, eigaret smokers bcflammation of the trachea and bronchia,! tree, tween the two groups is statistically significant,
MORTON L. LKVJN
V7Y-
;uul the indicated relative prevalence, from these data,, of lull}? cancer among smokers compared to nonsmokers is still considerable (approximately five times as great).
Because the routine method of obtaining smok ing histories is known to understate the preva lence of smokers, there is reason to believe that these estimates of relative risk are too low rather than too high. These data confirm those of previous reports from Roswell Park Memorial Institute5'6and by many other investigators that the lung cancer risk among moderate and heavy eigaret smokers is several times th at of nonsmokers.
Eliologic Significance
The fact that eigaret smokers suffer an appreci ably increased risk of lung cancer does not of course amount to proof that this increased risk is caused by eigaret smoking. It could also be due lo the fact that eigaret smoking was in turn as sociated with some other factor or factors which were carcinogenic or that eigaret smoking en hanced the effect of other carcinogenic factors. Possible factors of this kind which have been suggested are atmospheric pollution by in dustrial wastes, engine exhaust fumes, dust from tarred roads, and occupational exposure to carcinogenic, dusts or fumes or radiations. The air of some industrial cities is known to contain benzpyrene and arsenic, and mortality rates from lung cancer are higher in cities than in mini areas in this country, in Kngland, and in Denmark. However, this would fail to explain the marked excess incidence of lung cancer among males in cities as well as in rural areas. The extensive British studies of Doll and Hill6'10 also showed the same excess risk among smokers when attention was conlined to residents of London. Doll10 has recently re ported that t he lung cancel' incidence among nonsmokers in Knglandwns about the same in London as in rural areas and in females as compared to males. These findings suggest that the difference in lung cancer incidence between the sexes and between rural and urban dwellers may be due to differences in the prevalence of eigaret smokers in these groups, either alone or in combination with other factors. It has not been established that exposure to air pollution, to engine ex haust fumes, or to dust from tarred roads is significantly higher among lung cancer cases than among the population from which they come.
filing cancer cases known to arise in occupations
which involve increased risk to lung cancer at
present account for only a relatively small per
centage of the total cases. Admittedly, there
may be many more such cases than are recorded
and more such occupations than are now known.
Two studies correlating smoking history and or- |
cupation in lung cancer cases have been reported.
In 1,357 male lung cancer cases and 1,357 i
matched controls, Doll1 found an important ex
cess in the cancer group in only one occupation,
the production of illuminating gas: "The cancer :
group containined 23 such men, the control group
14.'' Although this difference was not signifi-
cant, it corroborated other evidence (gathered
also by Doll) that gas workers have an excess risk
to lung cancer. Breslow2in a study of the smok
ing and occupational histories of 518 lung cancer
cases and 518 controls found 77 lung canper eases
(about 15 per cent) "had an exposure of more 1
than five years to suspect occupations." In one :
of these, welders and sheet metal workers doing
welding, part of the excess risk was attributable
to the high proportion of smokers, and a signifi
cant portion could not be so explained. Unless
occupational hazards causing lung cancer are ;
many times more prevalent than any existing s
evidence indicates, they could not possibly ex- ?
plain more than a minor fraction of the observed 1
increase in lung cancer or the excess risk among i
smokers.
1
This conclusion has been further tested by a !
study of the occupational histories and smoking !
histories of male, lung cancer patients and other t
male cancer patients at Jtoswcll Bark Memorial j
Institute. In this study (to be reported more (
fully in a subsequent publication) 137 male lung f
cancer cases and 390 control cases were matched I
for age and place of residence and adjusted for of- i
cupation. The excess of eigaret smokers among ;
the lung cancer cases remained after the factors of j
age, residence, and occupation were equalized ;
(Table VI).
|
Interpretation of the etiologic significance of : the smoking-lung cancel' association rests on several types of evidence. First, it conforms ' with what is known about other carcinogenic agents. Tobacco smoke is known to be an irritant and to come into contact with the bronchia! mucosa. All or most known carcinogens maybe classed as irritants, although the reverse, is not true, and direct contact is one of the most fre quent modes of effective application of carrino-
ETIOLOGY OF LIJNG CANCER: P R E S E N T S T A T U S
T A U L F , V f . ---- K h T I M A T E I ) H K E A T I V K U l H K O K T , U \ 0 ( , ' A N C K H R V S m O K I N O C ' A T K C i O K I K S A N D O C C U P A T I O N ( M m . K S )
rnadjustod for occupation fumg cancer Control (othoi cancer) Ding cancer incidence among cig.vet smok ers co m p ar e d to nonamokers
Control cases a d j u s t e d to occupational distribu tion of lung cn. iver cases
bung cancer incidence among cigarc' smokers compared to nonpmokers, a d j u s t e d for occupation
Nonsmokers
Other than Ciyarcts
o.ii 24. 24
8.03 28.28
1.00
1 .33
23.02
27.81
1.00
1 .32
Sm oking ( 'ategories
........................... -
(Per Cent)
Cigarets b y D aily Units aiul D uration
^-- boss than
.--20 or M o r e - - '
20 per Dav Under 40 Years 10 Y ea r s or M o r e
per Dav Under 40 Years 40 Years or More
'Total Cigaret Smokers
13.87 10. 0 1
10.03 0.83
27.01 13.80
33.03 13.13
80.80 47.48
0.24 1J.87
3.20 0.38
0.21
12.71
14.18
13.74
8.71 40 . 17
3.32
3.32
8.04
I 1.30
8.03
'Total Cases
Num-
Per
her
Cent.
337
100.0
300
100.0
100.0
I'Piis. Second, it rests on the failure to demon strate other mown causes of lung cancer among smokers, as compared with nonsniokers, to explain the excess risk among the former. Third, and more indirect 1y , it rests on the conformance of the etiologic hypothesis with the known epidemio logic facts. These require that the suspected etiologic age it be one known to have increased markedly in prevalence within the past thirty years, as has cigaret smoking, and to have af fected males more extensively than females. The product .on of skin cancer in mice by tar ob tained from cigaret smoke, reported by Wyndcr, Graham, and Croningcr,4adds further support to the belief that cigaret smoke may be a truly ctiologic factor in lung cancer.
All of the available evidence thus indicates that cigaret smoking is one of the contributing causa tive factors in the production of lung cancer. It does not indicate that it is the, sole causative, fac tor or even chat it is operative in the absence of other factors, such as susceptibility and, per haps, other as yet undiscovered etiologic factors.
Perhaps Ihc fairest statement of the case, at present is that there, is a strong presumption that cigaret smoking is an important etiologic factor in lung cancer. I t has been estimated previously6 that in males cigaret smoking may account for from 50 to 75 per cent of lung cancer on the as sumption that other etiologic factors arc equal in smokers and nonsmokers. Recently, Doll" has estimated that in hlngland, "about one in live of the lung cancer deaths in persons aged twentyfive to seventy-four in 1950 were, attributable to causes other than smoking,'' or about 80 per cent to smoking.
A nticipated Results of Further Research
Total population studies, whether "retrospec tive" or "prospective," should serve to furnish more, precise estimates of the magnitude of the excess risk associated with smoking of various types and durations. Such studies cannot be ex pected per so to furnish more information than we now have regarding the etiologic significance of smoking unless accompanied by a concomitant stud.y of all other known or suspected etiologic factors for lung cancer among smokers and nonsmokers. Experimental studies now aimed at production of cancer in lung tissue by application of the components of tobacco smoke, if successful, may add to our confidence in the etiologic nature of the smoking-lung cancer relation.
Further study is also indicated of the, reasons for the much smaller increased lung cancer risk found among cigar and pipe smokers. Possibly, some sensitivity test may be devised to distin guish between the majority of smokers who may smoko with relative impunity and the minority who will develop lung cancel1. The, identification of and removal from tobacco of the presumed car cinogenic agent, without removal of tire tobacco, is a hopeful possibility.
Public Health Im plications
hung cancer is a rapidly increasing cause of death in this country. In New York State it now exceeds tuberculosis in number of deaths among males.
Retween 1931.-1933 and 1948-1950, ageadjusted lung .cancer mortality increased among males in New York State by 385 per cent, among
March 15, rio t
775
u IIIlim n
IITS ffl
MORTOX L. L E V IX
TABHK ('AVCKH
V I I . A<; r, -Ai ). Tr: sTKi )" M o h t a l i t v f r o m L u n d AVI) A b b O r i lK U S t t KH OK ('ANf.T.K IN' N k AV VllliK
S t a t i A ( D katiih pkh 100,000 Hiv in h )
T A H H F , Y J I 1 .- P kk ( + \ r I 'R o i i A i u i . r n o f l)FYF,bo!M'm H r \ < j C a n t k k a nd C a n d o r o f O t h f k S i tus f r o m B iutr n\
( 1 9 4 2 HO'f A\ i> 1949 H O I )
M ales 1931 -1933 1918-1.950
Females 1931 -1933 194,8 1950
Per cent change Males Females
Hung ('aimer
4.7 22.8
2.5 4.2
+ 385 + 08
( -;i tif'r r O th e r Sites
110,3 112,7
151,2 128.8
+ 2 -- 15
Site Male
All sit es Hung Female AH sites Hung
HM2 1944
1 .dd 0.91
19.37 0.22
1949-HIM
2 20..0117
23.27 0.34
1949 llio I (Adj usted'1)
18. 5(1 1 .87
21 .40 0.31
<' O b t a i n e d b y h o ld in g 1042 1044 m o r t a l i t y ra t e s from all ca u se s c o n s t a n t a n d a p p l y i n g 1040 1951 r e p o r t e d cancer inci d en c e ritt.es.
" Adjusted to 1940 population. New York State, t Kxclusivo of New York City.
females h r OS per cent (Table VIJ). .Since can cer is a reportable disea.se in New York State, it is possible to calculate the probability of developing cancer of various sites throughout the life span. For lung cancer, within the short period between 1942-1944 and 1949-1951, this probability has more than doubled for males (Table VIII). At present rates of incidence, 2 per cent of males may be expected to develop lung cancer. If the present rate of increase continues, this figure may double again within the next fifteen years.
Lung cancer is a public health problem rapidly mounting in importance. Public health authori ties as well as private medical practitioners must take cognizance of the available facts regarding its occurrence and etiology. The following ap proaches to the problem are indicated:
1. Case-finding: Since early diagnosis and treatm ent offer the only hope of cure in lung cancer, early case-finding should be intensified. Special attention should be given to the following groups: (a) males aged forty and over, (b) cigarct smokers, (c) persons exposed to known oc cupational hazards. The application of the community chest x-ray program, so extensively developed in this State, to the finding of lung cancer has already begun. Further refinement and adaptation of this program to the diagnostic problems of lung cancer are needed.
2. Public education: The public looks to the medical profession and to public health authori ties for information regarding health matters and for an appraisal of existing evidence regarding health hazards. W hat shall be our reply to questions regarding the relation between cigaret, smoking and lung cancer? The existing evidence justifies the following statements: (a) Lung can cer occurs more frequently among cigaret, smok ers, and particularly among heavy smokers, than among nonsmokers. We do not know exactly
how much more frequently it occurs, but the. evi dence we have indicates th at the excess risk is ap preciable. (b) In the absence of evidence to the contrary, the most reasonable assumption is that this increased risk is due to the effect of cigaret smoking, either alone or in conjunction with other factors, (c) Persons who arc concerned about lung cancer cannot be assured th at cigaret smoking will not increase their chances of developing the disease, (d) Cigaret smokers, particularly those past forty .years of age, would be well advised to have chest, x-rays taken at least once a year.
8. Research: Further research into causes, improved treatment, and methods of control of cancer is a public health responsibility. In New York State this has long been recognized. The expanded Roswell Park Memorial Institute at Buffalo12and the Bureau of Cancer Control of the New York State Department of Health are de voting considerable attention to investigation of the relation of tobacco to lung, larynx, lip, oral, and other types of cancer. Investigation is pro ceeding along the following two main lines: (nj investigation of the carcinogenic properties of tobacco smoke components and (b) epidemiologic investigation of the characteristics of persons who develop lung cancer and of smokers compared to nonsmokers in an effort to uncover all pertinent associated factors.
Sum m ary
1. The existing evidence regarding the eti ology of lung cancer points to the existence ol multiple etiologie factors, including occupational haza rds and ciga ret smoking.
(2. Known occupational hazards do not ac count for more than a relatively small proportion of lung cancel' eases.
3. The evidence regarding excess risk of lung cancer attributable to cigaret, smoking indicates that, it is several times that among nonsmokers
770
Now York State J. Med,
KTlOliOOY OF U 'X O CAXCFAt: J'lt.F S F X T S T A T X S
snd may a c e n u u i . for a. major part of the incidence <iflunp, cancer, ]>;u'ti<ailnrly among males.
4. Tim evidence for excess risk of lung cancer among smokers persists when comparison is made, between lung cancer patients and patients with uthcr conditions affecting the lung and bronchi mid when the :influence of residence and of oc cupation is equalized in lung cancer and control groups.
5. The available evidence is sufficient to justify public health action in the direction of mse-finding and public health education to the effect that eigaret smoking must be presumed to play an important role in the production of lung cancer.
6. Intensive further research in all aspects of the problem s urgently indicated. Further studies may be expected to provide more pre cise data on the magnitude of the excess risk to lung cancer among smokers. Additional evi dence regarding etiology may be forthcoming from the results of experimental studies but may rest in the final analysis on the study of other possible etiologic factors found in smokers but not in nonsmoxers. At present no such differ ences are known to explain the, excess risk among (lie former. The weight of the evidence there fore indicates that the relationship between rigaret smoking and lung cancer is causal and not merely an '`association."
7. In less than a decade the chance of de veloping lung ( anccr at some time (luring life has
more than doubled among males in New York State. Two per cent of all males may be expected to develop lung cancer at present rales of inci dence. Since a majority of adult males are cigarct smokers and most, of those over forty have smoked for many years, a good deal of the smok ing effect probably has already been exerted on these. Hence, no appreciable decrease in rates may be expected in the next, decade, even if everyone forthwith gave up smoking. Public health efforts hence must, concentrate on early case-finding and on research.
G r a t e f u l a c k n o w l e d g m e n t ip m a d e t o M r . A r t h u r K m us an d Miss R ita C u sh m an , of the B u reau of C an cer Control, N'ew York S ta te D e p a r t m e n t of Health, for assistance in the statistical analysis.
N oth : T w o c h a r t s a n d a n a d d it ioual I a h In will ho i n c l u d e d in t h e a u t h o r 's r e p r i n t s .
R e fere n c e s
1. Doll, R .: B r it . M. J . 2: a 21, 585 (Sept., 5, 12) ITT}. 2. Bres low , I,., I lo a gliu , I-., R a s m u s s e n , (J., a n d A b r a m s , II.: Presen ted at th e A nnual M e e tin g of the A m erican P ublic H e a l t h A sso ci at io n , Oct,., H)T}. I n press. 3. M u ll e r, kb II,: Z t s d i r . f. K re b s fo rse h . 4 9 : 57 (1939), 4. W y n d e r, E. L., G rah am , E. A., find Croninger, A. B.: Cancer Research 13: 855 (1033). 5. bevin, M. I,.. Goldstein, H., a n d G erh ard t, P. IT: J .A .M .A . 143: 330 (19.70). (>. Le v in , M . L.: A c ta , U n io n I n t e r n a t i o n a l e c e n t r e le C a n c e r , 9: T31 (1953). 7. W ynder, E. L., an d Cornfield, J .: N ew E n g lan d J. M ed. 248: 441 (10.73). 8. Co rn fie ld , J . : N a t . C a n c e r J n s t . 11 : 1.200 (10.71). 0. Dol l, R . t a n d Hill, A. B . : B r i t . M . J . 2 : 730 (19,70). 10. Ihid. 2 : 1271 (1952). 31. Doll, I t . : B r it . .J. C a n c e r 7 : 303 (1053). 12. M oore, G. E., a n d W eh r, W. II.: N u w Youic S tatk ,1. M m ) . 5 3 : 2 7 08 (1953).
M edictil Society o f the State o f Now York
Hotel Staller
A N jN . U A L M E E T ]
M ay 10 to i t, 1951
N U
New York City
March 15, 1954
777