Document 2qEKpGBbwvZO4LKyqL83DJNQa

FILE NAME: Smoking (SMOK) DATE: 1956 DOC#: SMOK003 DOCUMENT DESCRIPTION: Journal Article - Etiological Problem in Human Lung Cancer i Site July--August, 1956 \ C) I ; M ! !) X ! J M B K R -1 M u ! IMjL A J o u r n a l o f t h e A m e r i c a n C a n c e r S o c i e t y fl I "vf't i fll S'*I 's !l J . B . L I P P I N C U T i C () M P A N Y PH I L A D E L I' ll) A i /OT* ills !I !<)!.( x .iC A L I'ROBI ,U.M IN H U M A N P a v i . K. S i k i m it, m . i ). LUN'c; CANCUR | \ 1fJT)(1, 18,,`il,'! deal In w e re at u n b i l l e d to n o w n o t e x p l a i n e d hv a n y re e o g ni/e d exposing, I lm n ; i a m <t m i l i r U n i t e d .Slates am ong' o r o t h e r lat toes, a n d th e v a t e designat e1 1 ` V ' l.'i] l i m n all ( a u w x III a p o p u l a t ion ol " s p o n t a n e o u s "- - a n o b v i o u s a b s u r d i t y in a pit) n. HiO, 1)0 0 ,0(10 p e o p l e . " A s u r v e y in 11) f 7 s i t ;11 u n iv e tsi:. M a n y re c e n t li nes ol in vest ig " : an .I I '. 'IS le.1 i iu- N a t i o n a l ( a m e e r I n s t i t u t e in li o n h a v e o p e n e d th e p o s s ib i li t y ol j c r o i m i i i g c i i A m e r i c a n l i l i e s repot led ( e t u d e ) piilmo- lo r this g r o u p . H o w e v e r , th e n u m e r o u s lead' iai \ ( a m er-tnoi t a li t y tales pe r 10(1,000 w h i t e h a v e in creased the a p p a r e n t e o m p le x i t v ol flu' p o p u l a t i o n ol l.-t.-l in liii m i n g h a m , la.ft in p r o b l e m . T h e t u r r e n l s i t u a t i o n re se m ble s thai T l l s b m g b , l e d in D a lla s . I S ..'5 in D e t r o i t , 18.0 of " p i i n i n i o i t i . i " in a b o u t th e y e a r 1880. when in ( `.hit ago, '.11.8 in P h i l a d e l p h i a , an d '.111.0 in its n u m e r o u s e t i o lo g ic a l agents w e t e just he New O i l c a n s : in t l n e e ( d i e s in \vhi< h the hgnre.s lot w hites a n d n o u w h it e s w e re com- g inning to he separated out and identified l a the sin g le -h a t tei ia l- eo lo n y let h n it |u e , the list h'ined, th e tales w e r e 8,0 in .\11a 11!a , h i .8 in D e n v e r , a n d 00.8 in S a n Id an< im o .15 it is not know n to what extent these large dd lcrcnccs ate teal hut, in a n y c u m , the m o r t a li t y is si/e. title, l l t e t isk ta n he ex pi eased j n a not her sim p le ol K o c h 's po st ula te s, a n d e p itle m to lo g it a m e th o d s. R e l i a b l e m e th o d s l o r p i o v i n g tlu . i m p o i t a n e e ol suspetted agents are, however not set a v a ila b le iu lu n g (.in ter. T h e re c e n t i d e n t i f i c a t i o n ol 0,-1-heu/pvi cue , a potent c a rc in o g e n ic agent, and o th e r amin.t tin < S1-1' Iu. 1K-t I >( lot tn. <)! evet v 100 ha I lies hot n in this c o u n t r y , neat Iv two w ill u ll im a i c l v d evelop hint; ran lit': 'C t. m ostly h e lw e e n :>0 an d 80 years ol age. In a n v disease h a v i n g sin It a s m a ll a t ta c k ra te illto ,<nd o n lv a lte r so long a tu ne, t e t o g u i l i o n ol ,,: the e t i o l o g u a l la etots is e x tr e n t e lv tliiiienlt, ! .11 e s p e c ia lly il they are m u l t i p l e , if o n l v inter- i n i u e u t l v pre sent, a n d il th e lo n g i n t e r v a l iiu11, I out h i i t h to disease vep iesents the im h i e t io n 1 me l i o m t u m u l a t i v e H it s is, T h e p r o b l e m is <j u i I <d i l l e i e n l l i o m that in tin at me, disease, s ik It as measles, in w i d t h n e a t l y 100 p e r cent ol petsons are attacked, usually w it h in the lust ten seats ol lile. slto tlh a lte r exposure to tlie e t i o l o g u a l a g e u l. an d h\ an ag ent that lias m u l t i p l i e d a n d d i a l is p resen t w h e n the t lisease is m a n i I t s i . d lie p io h le m ol the eiiolog v ol lung taneer is g i e a l l y c o m p l i c a t e d hy the p r o h a h i l i t y that dem. th ere ai e m u l t i p l e lat lots. T he o cca s io n a l mat < Il li n o is that (it c u r in t l t i l d h o o d (see l e l e r e u e e A/l-ll It) lo r re leren ees) are h a r d l y a t t i i l m l a h l e to the sa me agents as ate those h m n d in u r a n i u m a n d t o h u l l m in e r s o r in ashe.sto.s-, chro m ate -, or 11: tit; kt1-, tar-, atid o t h e r spet iai w o r k e r grou ps.1,1 T h e gieat m a jo r it y ol in d i v i d u a l eases are t.) I: liom ilir lV|>;nhnml of I'.il linlogy, Thu University o{ C.huiiRo, ( .hit aj.'.o, Illinois. I hr basic woik was stqjpni lr<( iu pait I>v a ^ranf. liom flic American Uan<er Not iriv, Inc., on i('ioiiiiiini(iaiion of ilir ( o m in ilU e on (.lowih of ilir National h Rr'ra K h ( o11n( i 1. 66-1 Received lor j>uI'I u al ion, Neplember lib', I Don. lit polycyclic h vd lo c ai bolts in soots and c a r b o n hint k sr'-7 assumes i m p o i t a n e e in v i e w ` ih;, th e g l o b a l p i g m e n t a t i o n ol h u m a n lu n g s l a ', a n i h i u c o i i c m a t e r ia l s a n d th e d c m o n s i i at inn n u n ol this c o m p o u n d in at m o s p h e ric d u s t s 1-ant! in a h u m a n l u n g .1'1 l a k e w i s e , th e (list covers' ol these carcinogens in cither common ' a t m o s p h e r i c c o n t a m i n a n t s , such as I lie limit's 1111 . proi, ol i n t e r n a l -combust ion e n g i n e s , 1" - a s p h a l t s , ;t a n d r u b b e r tires a n d o t h e r p ro d nc is ,11 provide'' additional possible sources lor etiologual agents h a v i n g a w id e d i s t r i b u t i o n . T h e site listical association between the use of lohatog a n d l u n g cancer"- ' s- presents a n o t h e r pus Nihil it y, w h i c h is g r e a t l y s t ie n g l h e n e d novthat a c a r c in o g e n , T-l- h e n /pvrcu e , has beet' id e n t if ie d in - t h e tat ol c ig a r e t t e s m o k e . 1-" In view of the pkgKora of possible agent'-: o n e c o n c e p t o l the c u r r e n t e t i o l o g i c a l s i t u a t io n -) tO) kilosell . Sri h i: ptuh I-., Still: 11 shot, in. m in the U n i t e d S t a te s m a y lie o u t l i n e d a b o u t ah lo l lo w s ( T a b l e 1). ?" From this annual total of approximately, m i g i tluce quarters of a billion man-years of exT postire to possible sources o l ag ent o n l y about;'-. I'.e ; 20,000 l u n g c a n c e ls o c c u r e a c h year. It is nut,:, k n o w n w h e t h e r these fe w pers ons d e v e l o p the getis disease be cause t h e i r p u l m o n a r y cells h a v e the, highest susceptibility to neoplastic iratisfo in u li o n , because; th e v h a v e h a d th e g-reaLcst ex p o su r e to c a u s a t iv e agents, o r be c au se these laetots ate c o m b in e d . N e i t h e r is it known': w h e t h e r the effects o f these a n d o t h e r h yp o -: .teste , 'ten ii have einj.: ..! - T g - - n > ,p - "- i- ^ w rT ie T > rT ^ 'u - "T M iin m m u u m m 'n n i- , No. Ki 101 nmc; si I'li'iui i m in I I m h :\ I. i'nc ( . w i l l . : Slcilll T aiu.k 1 H O M SN m . M O N A R V V . M ' O S t KW I D isI \ is!nil A\|) m oot lit: i K,\|. C.A 1\ ( I \ ( ) ( . I , N S r7....,r I \ |)i >m ire v iexjgnated fi m ,i phy- y n m s t i g a . i" ' i ' MIII I i l l g 7 ` "i-i h a n k , ;:! . i ;\ 'il 11K> i.i ddes dim. n >. w h e n y past he- i i died hv t di r ij.sfJ l " il<igieu] h iml; ilir t7 i V m v v c i ' . j: .' (>vi riu:, V' 1;i,,"na' i .mil car ; i icsv o{ ; '<nigs hv l 'I'liai ion : 11- 1si - -i ji, ; In' ills. ; Imi ni on J: 11niics a . -;i l uI l s, !i b | Hi Allies !j m >b>gu a) J "7 M;|-1 1 I l l u i l l ) il! ( KT [MIs "i I i ii nv (; ms been | ' .i >is11s, . i i n .11 ion ili'Hii a-, isin.alrlv Is ol ex IIs ,111'); i' ;i is nm m Ii>i> i h e !i, i\ c 1h e i i i 'l n i m;i .'.in s i c \ e e lhesr r iainivn 11! i 11\ | )(> Appmsimati n u m b e r nf per sons b r i nk exposed anmialls' ( o : .1, i di c n/ pyi ' r ne am] oi l i er e . i n' i nopens in sinus .l. i-lieiirps rene anil oilier livilrornt'IjdiiS in .alpine e x h u i M iiinirs. vl-benapYi'ene and n'dier li sdmrariions in asphalts, etc. i , t licnrp'aene and oilier c.iirinngrns Ml nilil'er proi Ilie is, sue 11 as (ires, el e. I tosilile e,;r ei nol ens in ( n h u r o prodarts aslie-aos rluomales !ar!;el oilier iinrrropiii/rd . w r n e . Hit),0110, 000 Hid,POO, (100 !( , f l ,0(10 , (10(1 )(ill, 000, (ton S.s.OPO, 01)1) j' > jend annua 1nia n \ r id ex pi om e, approx. ] oia! annual lunp o i i i n a s , .dionf 7.'a .000 . (0K()0P jii'Mii al ( In. mil al age nts :ne, in w h o l e or in part, additive: ni i i l na l l y i nhi bi t or y; synrtgi.sin; sinnina lalilt; to oi l i e r n n m e n i i o n e d ami , peihaps, noiispeeiln latlors; or whe ther they operate in 'dill o i l i e r tears. 17 | he dillr; til lies in pi n p o i n t i n g di e r e s p o n sible agent or bn tots in i n d i v i d u a l h u m a n jni iri am ris are gtcai. if. (or example, a serial number, b e g i n n i n g wi t h n u m b e r 1 a n d g o i n g ilirmigh In 20,000, teere assigned to each ol die lung c m i n n m a s as dies' s h o w u p o n | , m u ; u y | anil (Iteicallcr ol a m tear, (hr e l i o l o g i t a i problem would lie dial ol dete rm ini ng in ease ,lumber 1 (be relative i m p o r t a n c e o f eat It law lot in the list g i v e n a n d of o t he r s as vet u n known, Ti n same p r o b l e m w o u l d pi e s ont it self in case n u m b e r 7! and in each su c c e e d i ng sniped in l u m b e r 120,000. In n o !van eases, probably, n o i d d die i('.sponsible agents, their proportions, and their somites be exactly the wine. U is possible that b l i t h e r i m e s l i g a ; ion will To w that e u e or several age nts pi (' domi nat e in some, nr even in a ma j o r i t y ol, t asrs. T h e demonstration ol this tail w o u l d he easier il nunc ol the agents were e li emi tall v u nique. blirn/py iene lound in a lung with ( a m c i might have t o m e from o n e or sevei al soui ces, the ideitt ilu at ion ol t\ Im h tvould be <1rfftr 111( pv impossible. I he <hemi i a 1iy tm it pie t arcinogel is m Maide I were, t o i i se q u c u t | \ , di e first pi be v c e o g m/ ed . I. xtratls ul h u m a n l ungs ppled lor <an i n o g r n i e a i i i v n y , with no at K'in|)l at I m d o n a t i o n of die t o m p o n e n I s . 7'" I, ,vr yielded evit lcm e ol at t iviiy ()| i be degi ee , aipliasi/eil In1 Kenn. nvat as ol i m p o r t a m e ht human tai n er. Ilf,. 1, ( dill j ),l I i "Il "I Ml I \ p i11iMl r 111 ill I Ml ill'MU'll" sis p ll ]\ r " \ I in u ll ii 11 !MO pel i "Il I "i an iMl.IIs diu ciopisi 111M1111 in In" \r;iis. null jjiuiiM] lung i.ilioa (sue Irxlp In expe t u nc n l a l i at t i nogenesi s, il is possi hie, hv v , u s i n g t he t a n im ig.en, its dosage, die spet ies and ' l i . i i n oi annual, die tissue e x posed, a n d otliri I:i<tills. In a i l mw i lupli (Up to 100 pci l e n t ) ol low ( i pi "Ml, 111,, ii w yields in a lew months, Itespn. abilits i igitlly to ( i m1111 d die ex pup m i l l 11 al i olid it ions, the mi e r p i et a ! a m ol die n s u h s is s o m e t im e s d i l h i u l t T ' l l a s m g e x c i t e d its cll eit s, the i ;11 linog en mas he absent in dial ihcm ii a! loim wln'ii the n mi o i appe a l s . bin t b c t mn i e, die presence ol an agent know n to be t an inogeiiit does not rna (".xurdv p i o c e dial it will i n d i n e or lias i n d i u c d a tunuu oi (wen dial it is bi o l og i c a l l y at live. I. in ina< Iival ion ol T ' l - b e n / p y i c u e hv adsoi pti ot t to t a i b o n jiat- tiilesd mas explain whs the inhalation of a p p r o x i m a t e d 7100 /(g. p n vear ol ibi s ( h e m- u a l 1 does not icsull in a greater m n n h e i oi h u m a n hm'.; t a m e r s . 1 lie el i ci t s nj l.pt) pg. per scar ol d, ! b e n / p y i c n e in ( i g a i e l l e lais- iiniv also he m i t i g a t ed b\ tins phei lomei ii m ol I n o l o g u a l i n .k ( t\a ( ion, II I bO.OO.'I.OOO p e o p l e U s i n g m an e n s i i o n m e n t n! t a i t i n n g c n n a g e n t s d e v e l o p nnlv 710,000 l u n g l a m e t s eai h vear, impnilanl p io l e it is e l.ulnis imisl lie m operation. T h e h u m a n e t i nl og i ta l p i o h l e m is d i l l u u h not o n l y hiob >gh a 11S' a n d t l i c m n a l h lull al vi e p i d e m i o l o g u a l l s . T h i s is (Must i afed hv big. I. ( i u r v e " A " i c p i e s c n l s an r \ | ici !m e m in whit h 100 per (Cut cd the a n i m a l s u p l a n d w i l h a cart i nogen d e s e l o p e d timwa svillu'n two ve,u\. 1in i'i pi el at ion id di e l e s u ' i s ol this m a g n i t u d e iiuiv he c x t i e m e l v dilliiiill il s e s e i . d agents Itave ilia'll m n i l i i n r i l . 111 ( o n l i a s l , di e i n t s e lot lung cantei in a linnuiii p o p u la t i o n Ini lowed lor eights s eal s w ou ld lie i eju esential al. di e level ol 71 per ( c m , a p o n d so near the base line dial 0 cannot t sen he demonsl t ated by the si a le used i n ! ig. ] \ e \ e n heless, as was HU r n l l v p o i n t e d out bs Kc u n u n . i v, ltd-, is die o l d e r oi m a g n i t u d e in w.lmli il is m a w s , n s to thi nk in tiinn. m t a m ei e l i o l o g t . It is the d i l l u u l l lesel ol i . u i s a l i s e l a i t o l s that, the slatistieian and epidemiologist, the geneti< isl, a n d Ilie <Itemisf must wan k (\ it h. sepat ate, am! i d e m il y in In o g i a in er. () 1 i out se. Ihe e p itlend h i ih ( , , . \ \ c ; u I n l y . f ttgitsl i b d h \ M nlD'Ms! lists (>i her ic( Imujiirs by whit h lie ]ln| rs in si m j>! i Iv i hr ii n,i I\ sis. I i;i\ in;; idiih' this l.u, U m.iv he jno m issi 1>lc, (In' |>1 .iM(l d<si i ,i I)lr, 111 sj k'( n Ini r ;i I)i 1 Ini i Ikt ;ib<m I u b l c m m (hr e v c n i u d ( u n i i o i ni tun;; f ;i n it I>\ ]>i (u (11111 () u . I Ir i r Ilu'i (' is ;i i i c m <11111 ;r. jdl; in ]n u n i | >lr, j)i <>\ i<11uI by t \ | M'l i mcnl. il ( in ( inn;;riu'sis. T h i s is lo llu: el k s ( Ihit I iI is not nc< rss.n v io wi l 1T o l d ;i (Mi ill'w o n u .i;;rni (<>iu])I(IrI v (o prevenl a c a i u r i . bui oul\' in u o l m c llu* c x p n s m e bclna a ( ( 'Main i hr c s hohi i e \ e b 11 tlu' small risk ilia', man has to Iiiiil; c ancer represent s the woir b i n a i i mi nl highest s'tisi. rpl i bi li lv j>1ns op <di l e d. Tunm-. (he p io b l e m ui pievent mn l i u o u i r out* nl a I m i h r r slight. m l m i i o n in i \ p u s u u bv w i t h h o l d i n g a part ol (hr present iv ;u litia^rni or a^rnis. 1 jns w o u l d b e c o m e a lopiur (.onsrtpH'iK c nl siirtesslul ellorls ideii 1d vinil and assign I ( o n c< t roles lo r;u li arrii 1. Pn h<n (: Mull i(i 11: K I I I Rl I. \ \ < > v ( .ii t iimmmiis in i ia.i i r i i cs. [ I'.dilui j.il j U)i ( . m. i i m :i i m i . l o o t , d. ( .( m|-i k. K . I I .1 \ l M , ,\ . | . ,l |]( I \ \ \l l l K, Is . I'd: I iir |.ICS, IKr ,| S; 1 Iui i/1>\ i cmc iii ( jj>,ncl Ic mm>ke. f I r'l | ri in i h e 1.d i 0>r. j ('.In / u . A I n d u s ! . [ I07 I j: I M S , I'M. a. ( . e m u . s. p, a n d I ,<>\ i i w n , I). 1',.: T h e ' i isk o f dcv c 1oj 1111,> 11 1 n lm .1111 ei a n d in. i > 1.1 1i, ins 1i i ]i l o s m o k i n g . /. \ u t . ( m u , r , h i s t . I 7: r i d ' l l . 1W, I. I. ! X >i i , I s a n d I I n l , A \ \ I lie m o l la Iil v ol d o t i n i s in i c l a i i n t i in i h e i r s m o k i n g h a b i l s ; a pi e! i m i nai v i c p o i i . l i n t . M . /. I: 1-17 I I I.V,. 1071. 7. I u K. i I . I a n d S i i m i ; , I'. I .. nl a m m a l n p n l w w l i r h \ d 11 x ,i i h m is hr n i t f i I h n m n h Id: .70 70. ) o ,'J. I h e i d e n Ii Iu a Ii on in tarbou hlaiks. >. I \ i K, II. I S u n k , l '. I ( . m m i i \ . S.; I'.in si o w , \ . a n d I M k i s , R. : ( 'a i < i ixmm i m 11\ d i ot a i l i m n a n d u ' a l c d i ni 11 p m 11 k Is in p i o t e s s e d i n h h c i . C u / n r i I l c- snndi 11: :i:m . iwm. A ( . o n in\. I'., and ' l i n m \\. Ma V'.xpn interns in l ; id, 111i 11<j i i on ol 7: | I)ci i/ p \ i c u e in d o m e s I ie s on l I>v m e a n s oi i h e Ii i m i cs, ei u c s p c i i i m n . 00 h . /. ( um<<> Id I; 7 - Ihi', I!) Mi. S. I I \ \ i \in.Mi, IT ( ., a n d I I, iK\ . I n. 1 h e i cl a l ion.sii i p liMween h 11111,in sm o ki ng hahils and dcaili laics; a h | | m \ n p s i n d \ oi 1x7. 7oO m e n . /. T AI, I.>.>: l a i n i :a m . 1(17 1. A. I l i i e i k , W, l : O m i p a i i o i u ! I l l i n o i s a n d A l i n 'd Ihsi.iscs, Xpi ino!id, 1. Illinois. ('mules (A 'hom.is, 1(1IM. in. I h m -ii o W . (d: I ' m i i o n m e n i a I i o n ; ; I n d u s ! . , \ h d . d 7 / / 0 - dO- I!) o. d I ' . M. laiuiT. I I . k i \ \ \ \ v \ Y . Id: I h e s i ; i l i s f na l s i j n d h t a i u e ol h n l n ^ i i a i d a l a . I n i ! . M . /. ' J : on",. 10.) I. 10. \d: k o n \ , I' .; I- \ i k, II. 1 \ I \ hi k. Id. a n d 'I i i o m a s , \ 11 .ii i.11 it h u t ioi a i h o n s . 1, I'icm u i r i ntin I.o> N( IS Animles a U n o s p h ei e and ihe i a u iix>oenit iI\ ol Tilin' p h e i i< e \ 11 at Is. . I . Ah . I . / ><h . I n d u s ! . 11 v-.;. 0: 1 >A I 10M. im , 1' I;11 Id. K 1 111 \ , Id: i \ i k . II. I... a n d I n o \ i \ s M. : Ai" m a i i i Ii \ d i o, a i Iam-. II. 1' i e s e i u e in ( h e p . o i i o i l a t ' p h a s e o | g a s o l i n e e n n i n e esl i an. sl . s a n d i h e i a u i no^ei i i i ' i l \ , >| e v h a u s l e M i a i l s . .1. M . .1. A u h . I n d u s ! . / / \ d . il, Hill n 0: Hi! 177. I07 I. M.,s. I !. 10 in n : 111 \i m Si r \ mi . D i e \ k i m i n i ni n Ie wI ! n n 1 d k n r i \ n o \ , a n d W i i )u u : Y i f a l S l a l i s l i e s o l llu* 0 I.''!<ni:loO Mal es 1070; V o l u m e III. M o i l a i i l v Dal a. Wdisldneler. . I).( . ( . o \ e i n i n e n l i O i n l i u g Of l i a*. I(k`)!d t.`d'(.)i i : 17. 10 in u: H i u . m S\ rvii r. h u i ' M . 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