Document wqQgjNJaJ39wDV2b67w724KQ

FILE NAME: Kent (KNT) DATE: 1956 July-Aug DOC#: KNT145 DOCUMENT DESCRIPTION: Journal Article - Etiological Problems in Human Lung Cancer - Cancer i Site M u ^ ,, ,,fi M1* July--August, 1956 \ C)!.( ; M I !) X !J M B K R -1 ft MSL A Journal of the American Cancer Society fl I "vi'i I ill i'* I '' s !l J . B. L I P P I N C U T i C () M P A N Y P H I L A D E L I' l l ) A |i /o t * wfPsh, A filli ! I !<)!.( H . i C AL P R O B I . KM IN H U M A N l'.-Vl :I. H. S IKIM It, M.l). UINO CANCKR |\ 1 1.S, I,`i deal In were a t t r i b u t e d to now not e x p l a i n e d bv any recogni/ecl expostm.. I linn; i a m <t m ilir I T i l e d .Slates among' or o t h e r lac tots, a n d thev a t e designates ' ''i'.' I.'i] li mn all causes In a p op u l a l ion ol "s p o n t a n e o u s " - an obvi ous a b s u r d i t y in a pit) n. HiO,000,0(10 p e o p l e . " A survey in 1i) f7 sic al tutivetsc:. M a n y r ecent lines ol mvrstigw an.I I'.'IS le.1 i iu- N at i on a l (l anc er I n s t i t u t e in lion have o p e n e d the possibility ol ac eouniia,- ci i Ame r ic an lilies repot led ( etude) ptilnio- lor litis gr o up . However , the n u m e r o u s lead' iai \ ( am er-tnoi tality tales per 10(1,(100 whi t e have increased the a p p a r e n t eomplexi tv ol tlit' p o p u l a t i o n ol l.a. l in liii m i n g h a m , la.ft in p r o b l e m . T h e c u r r en t s i t u a t i on resembles that T l l s b u i g b , l.u.O in Dallas. IS.'! in Detroit , IS.O of " p n e u m o n i a " in a b o u t the year 188;). whet: in ( `.hit ago, 81.8 in I'll iladel phia, an d `AD. A in its n u m e r o u s etiological agents wete just hr New Oi l c an s: in linen ( d i es in with h the g i n n i n g to be s e pa r at ed out a n d identified l a l-gurrs lot s\-11itcs a n d n o n u l i i t e s were com- the si ngl e- bat tet ial-eolony technicpte. the list h'ined, the tales were S.O in .\ 1 1a 11!a , I I.S in Denver, a n d 80.8 in San Id a n< im o. 15 1 is not known to what extent these large diilcrcnccs ate teal hut, in any e \ t n i , the mo r ta li ty is xi/cahlc. rite t isk t a n he ex pi essetl in a not her si tuple ol Koc h 's postulates, a n d epidemiologic .r me t hods. Re l ia b l e me t h o d s lor p t o v m g tbe i m p o t t a n e e ol suspected agents arc, however not set available in lung cancer. The r ecent identification ol 8,-l-bcn/pvt cut'. , a potent cat ( biogenic agent, and oilier aroin.r tlu < 1 I tc . 1K-t l i( Ionn. Ol evei v 100 babies hot n in this eonnt ry, neat Iv two will u ll i ma t el v devel op l u n g can ' et . mostly bet we en :>0 a n d 80 years ol age. hi anv disease bas ing -ate b a small at tack rate .<ud onlv al ter so long a tune, t e e o gu i l i o n ol the etiological laetots is ext rentel v eliiiuult, especially il they are multi])le, if onl v interm i n e u t l v present, a n d il the long interval I om biitlt to disease repiesents the induction 1 me horn (umulativc elicits. T h e problem is (|uilc dil l ei eni lioiu that in an acute, disease, su< li as measles, in which neatly 100 per cent ol pet sons are at t ac ked, usually w i t h i n the lust ten seats ol lile. s lt ot l b a l t e r e x p o s u r e to lit polycyclic bvdtocat boos in soots and c a r b on blacks'' -7 assumes impoi l ance in view w the global p i g m e n t a t i o n ol h u m a n lungs la', a n t h t a c o i i c ma t er ia l s a n d the dcmuitsl t at ini', ol ibis c o m p o u n d in at mospheric d u s t s ' - - a nd in a h u m a n lung. "' lakewise, the (list covcry ol these carcinogens in ot he r common ' a t mo s p h e r i c c o n t a m i n a n t s , such as t he limns ol i nt e r n a l -combust ion e ng i n e s , " '- - ' asphalts,;t a n d l u b b e r t i n s am! o t h e r prochn is,1' provide' additional possible sources lor etiologual agents havi ng a wide d i s t r i b u t i o n . 1 be sta lls l it <cI association be t we en the use of lobaeeetpa n d l ung c a n c e r 1- " s- ,'1'- presents a n o t h e r pos ` ib;, lit-;- nun lino fill,,; ! at. plot, II I II : tO) kilo-, sell , 5u 1)V pin!, the etiologual agent, and b\ an agent that lias m u l t i p l i e d a n d that is present, w hen the i lisease is ma n i h si. 'I he p i o b l e m ol the etiology ol lung tatteer is gi eall y ( (i mpl i c at e d by the p r o b a b i l i t y that t here at e m u l t i p l e lai tors, ' he oeea.sionttl stbilitv, whi ch is greatly s t i e n g l b e n e d now r " - f that a ca r ci noge n, XThc n / . p v r e ne , has beer .Uli: ide n td ie d i n - t h e tat ol ci garette s m o k e . ' - - 11 In view of the p kgKor a of possible agents. A shew, o n e c o i K c p t o ! the c u r r e n t etiological situation-, in. m in the: U n i t e d Stales may be o u t l i n e d a b o u t as dent- tumors that o i e u r in childhood (see leletcuce It) lor relerenees) at e h a r d l y a t t r i b u t a b l e to the same agents as ate those lou n d in u r a n iu m a n d cobalt mi ne r s or in asbe.sto.s-, chr omate- , n i ; kel-, tar-, a ud o t h e r spec ia i w ork e r g to n p s. ' " i lie gieat m a j or i ty ol i n d i v i d u a l eases are l ion) lli<` Hcpiu Iiijcnf of I'.ii linlogy, Thr University o{ (hua^o, (.hiiaj.'.o, Illinois. I hr hiisir woih was stippni led iu pait I>v a ^tauf. I i o i i i !hr Amerit ari (aimer N<><ieiv. Inc., on leioinmentiaiion of liie Commiltee on (.muili of (lie National Rf-ra u li ( cii iu iI. Reteived lor j>ull u aIion, Neplrmber HJt'. lollows ( T a b l e I ). ? " From this annua! total of approximately", tluce- q u a r t e r s of a bill ion man-years of e x T po.sure to possible sources ol agent only about;'. 80,000 l u n g cancels o cc ur each year. It is nut;., known whether these few persons develop tlu disease because t h e i r p u l m o n a r y cells h ave tlu., highest susceptibility to neoplastic iratisfoinu lion, because thev h a ve h a d t he greatest, ex pees tire to causative agents, or because these laetots ate combined. N ei t h er is it known': whether the effects of these and other hypo s KM ( A TI; migi ite ; or it, g'-lls DO b testi . tet u t haveetnj.: ..i b 66-1 Miinmmuumm'nni-, u. K i 101 i >c.o ; si I'koI'.m m in H u m s n I . unu i '.w u h Slain T aiu.k 1 m :M IN r n. MONARV Xla ml R I d i s I \ !s| il il a \ [i h v I'o t i i k i K Ai. c \ k t i \ ( it .1 \N r ...., r I \ |)i im ire v m ,i phy- y investiga. | i mm l i ny t ' m-i leads ;:! >ii\ 'il l 1k> i.i '. M h t h a t N when y u\i he- i Appmximati number nf persons bring exposeal .uiim.illv (o: A, 1-heii/pyi'i'iie anil oilier carcinogens in son is s.-i-ln'iirp;, rene and oilier livdroenrbinis in engine exhaiM ionics. A.'l-benzpvreiie and oilier lisdroeam iimis in asphalts, etc. A,-t-hciU'p'aene and oilier carcinogens Ml mill'IT 1in IIIue 1?, sue II as Iires, el e. I uv-il'lc carcinogens in tobacco prod ucts ,1 (C-AIIS rlironnOes ns'licl oilier unrrengni/e<l agent!. liit 1,000, not) Hid,(100, Odd !f>(l,000 ,(KKI 1(ill, 000, Odd N.s.OOl), Odd ' > i d ual | )\ \ rial annua I ma n-\ r of expoon e, approx. V.'.s .000. tint) d i r ij.sf1 ],iia! anmi'd lung eui ros, ahouf .((I. d( (1 1 1 ' i l <i g l e a ] h ' im g Il i r k ieii( nl r hr 111 i( a I agent s aie, in whol e o r in !>W( ' \ X T , j: part, a d d i n ve: n i i i t na l l y i n h i b i t o r y ; .syneigi.s- Iu ; siimma table to o t h e r nniiienl ioued and, . ' (Vinif;, V' if. |,el haps, notispeeiln hit tors; or w h e t h e r they 1 a t om; , - j, .uni car ; i icw o{ i operate in 'till o t he r wavs. 17 | !ie dillr: ullies in pi n p o i n t i n g die sible agent or (a<tois in i n d i v i d u a l respon human ' by l i' i ) a l i on ins! V- -1 j|, I!a' ills, 1 Imi l l i on J: IIHI UN \y - ; i l u I i s , !i -a | u iniil cs f 'm!r>r;11a1 | Ihc M , J 1 I I l ! M 1 ( () S I K T ; MIS- I ' I - I H O W (I mieiaiHias are gicat. if. (or example, a serial number, b egi nni ng with n u m b e r 1 a n d going (hrmtgb to dO.OOO, were assigned to each ol the lung omiiintiiiis as tbev show tip on | . m n a i y | ,eid then, al ter ol a m aear, the el io l o g i i ai problem woul d be that ol d e t e r m i n i n g in ease uuniber 1 the relative i m p o r t a n c e of ok It law tin in the list given a n d of o t h er s as vet u n known, T i n same p r o b l e m wo ul d pi c se nt it self in ease n u m b e r '1 an d in eueh sin ( ce di ng subject to l u m b e r '20,1)00. In n<> two eases, probably, o o id d the i ('sponsible agents, their p;ijja it t.io 11s a n d t he i r sou tuts be exact ly the M ' b e e n f s.ti: iv. U is possible that fin liter i nvestigation will .i >i'111s, -i i na i i on a bout ;i, 'dniw that c u e or several agents pt ( 'domi nat e in sonic, or even in a m a j or i ty ol, t uses. T h e demonstration ol this tail w o u l d be easier il lente ol the agents were r h e u m alls' unitpie. - .; n .a Ir 1v ' 'll I N I'. ,111o :11 Idtcn/p; ri'tte lound in a lung with innccr might have t o m e from o n e or scveial somccs, lie uleilti/n at ton ol t\ Im h wo ul d be <i rffir 11 i( li is 111II uv impossible. I he <hcmii a 1ly u n (pie cat a ino i ||)|) tin; M i l 1 1he m-iis m Mable I were, <oiiseijucntIv, the fust m he recognizee!. | . \ t r ; o t s ol h u m a n lungs m h o) lll.'l (csted Im' <a u d i o g e n i c a<iiviiv. with no at e . i u si e \ mi Ihese iciiipl at 11 at Iinnat ion nl the i o m p o n e n I s . 7'" I, ,vr yielded evident e ol at t i\ it v ol t he tlegi ee r Jimvil 1I! I 1 I \ I ) ( ) , mphasizeti bv Ke i ma w . n as ol i m j i o r l a m e in human ( tun er. I l f , . 1, ( u n i j i.i i i hi o u n i x p u i i m e n l i n u r l i i n o g e n e si s (i u i \ e " A 1 i n u ll ii II ! Md s i i e n i ni ai i i m. i Is de \ ei o( ns ) h i n m i i n I n s \ e ; n s . w i t h Jj 11 j j i ;i l j l u n g i . i m e i |sue l e x l ) . In expet menla! i a) t mngenesis, it is possi ble, by vat si ng t he ( a i <)in igim. its dosage, die species a n d s o , m i ol a n i ma l , di e t issue e x posed, and ntbei lailols. In ai lneii lueli up Io I0(1 pe i i111) or Ion I i pi an, 111,, a a vichis in a leu months. Itespi,. abilns l igidly lo ( ( ii 111 ol die ex pel unci 11a I ( olid 11ions, the itllcrpi clat ton o| die lesiills is s o metimes di do u It. l:' I l.n n g e x c i t e d its elicits, the tat- ei nogen max He absent m dial i b e m i t a l h u m w h e n die m m o i appe al s. but tliei Hint e, die p r es e n t e ol an a g e n l k n o w n to be <ait biogenic does not necessarily p i o e c dial it will inline o r lias i m b u e d a t u n m oi even dial ii is biologically at live. I.iic i na c t i va t i on ol Tl-beti/pyi cue bv adsni ptioit (o taiboii par lisies''7 mas e x p l a i n whs die i n h a l a t i o n of a p p r o x i m a t e d 200 /<g. pci sc ar ol ibis c h e m i c al 1 docs not icstill in a g r ea t er tiiimhet ol lunna i i l ung ( a m els. 1 lit elle< is ol l.hl) //g. per scar ol a, ! b r n / p \ i c n e in ( i g ai e ll c lais- 111;ts' also be mi t i g a t e d b\ tins plienomeiioti ol b t o i o g n a i iliac (i\a Iton. II I(it t.(KKI, 0(1(1 peopl e Us ing in an e n \ ii o n m e n t ol ( i n t i t t o g e n u agents dev e l o p onlv gU.UUU lu-tig i . i m r i s eat It year, itnpoitanl pio te ttise latlnis must lie m operation. Idle h u m a n eiiological p i o h l e m is d ifii<1111 not nils' biologo a 11\' a n d <hem n a ll\ but also e p i d e m i l o g o allv. T i n s is d l u s i i a i e d bv hig. I. ( ni r ve "A " l e pi es enl s an cxpei i ni e m in whit Ii 11)t) per sent o! the a n i ma l s i u j e c t i d svilb a cal a ungen d c s c l o p c d lumo i w it hi n two visits. 1lit ei a el at ion ol die t e s n hs ol this m a g n i t u d e mas' be e xt i em e l v dill oull il seset.tl agents liave been uiniluned. In (onliast, the ttu s e lot lung e a to e i in a l i i i nmi popt t l ai i uu Ini lowed lor eights seats would be t cju esented at. the level ol L' per <ent, a point so nea r the bast' line that it ( a n n u l <sen he demons l t at ed by t be sea Ie used m I*ig. 1 \ e \ ert bcless, as was i c i c n t i v p o i n t e d not bs ixcu na u a v, this is die o l d e r oi magi 111n d e in wi m l i it is hcmns.iis to t h i nk in h u m , m t a m ei etiologs. It is the di l l oul l lev <I ol (.ausatisc h o t o i s that, the statistician and epidemiologist, die genelit isl. a n d Ihe <berm si must wm k wi( h. sepa tale, and i d e m ii y in Iu ug i a in er. () 1 t <uu sc. the epidemi- h i ih ( . A \ ( v n I u ly . f tigasl DT>h \ nl n l D ' M s ! lists (>i h e r let i mp l i e s hv whi t h he ]in[ rs in s i mpl i f y i h r II n,i I\ sis. ( d i i u e i . h u i o u l \ ' (u l e t h u e lilt* c n j i o s i i i c Ik 'I* a ( ( 'M a i n t h r e s h o l d i r \ r h 11 t l u ' s m a l l r i s k 1h;it I i;i\ in;; t o m e t hi s l. u, U m. i v he pel m issihle, .iM(l d<si i ,iI hr . In sj >(( n In i r a hii I m i he) ;i h<m I lh<- | u n l i l r m m ( h r cvciiii! tl t m U i o l nl tun; ; f i I K <T I>\ ])i t a (nl l m u . I I r i r I ht.'i r is ;i i i r n<11111 ;m.j d l ; ; m ; i l n i ; v , i n | n u i< i j >lr, p i o v i t l r i i h y ( \ | M'l i m r u l . i l ( in ( i n < > ! ; r n r s i s . T h i s is l o ( he: (lift ( i hit i 1 is n o i n e t r s s . u \ i <> w i i h l u > k l ;i ( ;m ill' :);.;(in< . i ; ; r m t ( >m j >1(lei v t o p r e v e n t a m a n has to l i m p e a r n e r r e p r e s e n t s ( h e tornh i n a i i n i i n l h i g h e s t s*t i m. e p U h i ] i I v j >1u s ;_n e a !("'I. dosage, the p io h le m ui p te v e n lu m hetuear o n e nl a Ii i i i Ik t slight, m h i d i o n in i \ p n s u u hv wit h h u l d i n * ; a p a i l ol t h e p r e s e n t iv at litia ^ e n i o r a ^ e n i s . T J i i s w o u l d h e r o i n e a l<>';i<e (.o n s e t p H ' i K e nl s i i e t e s s l u l e l l o r l s i d e n i i l v i n d a n d a s s i g n Itm t nia et ! r o l e s t o e a t h a r e 1 1 1 . rn ,y<n (; Mull ion; Ri I I RI I. \ \ < > V ( ,Mf I1MMM11S in ( jn.1 l ('ll (S. [1',(||||)| j.il j U) i ( . m. i i m: t ioi i. l oo k d. ( ' i i n n i>, K .I I .i \ i m . A . | . ;i n<j W \i i i ie U . Id: I i i r | i c m i n ( i >1 a : ! I >et i/1 >\ i r u e i n t i14.11 c l I r s i n o k r . II 1 'I I n In Ilie 1.(Iilor. j ( ' h i m . I n d u s ! . [ IUS 1j: I MH, i'.l. :t. ( . e m u . s. p, ;ui(J I ,(i\ i i \ \ n. i ). 1',.: T h e 1 isk of iiivc 1<1 1 1 1 1 1 n 11 1 1 1 < .m1 1 r 1 ;m 1 1 in.1 >1.1 1 i<1 ns 1li1 1 Io s moki ng. /. A at. ( m u , m I ns t . I d: L!() I J I I . IT, 1. I. ! ><>1 1 , R a n d Un i , A \ \ I h r mol l.i Iil v ol doc fnis in irl.i i i nn in i hr i i smokin' .' h;ihils; a pi c! i in inai v i r p . n l . H u t . M. }. I: I Idl I i.V>. Iddl. d. I u K, i I . I a n d S 1 1 1 \ i in R. I ' 'I h r i( frn l ilmi lion ol a m m a l n pc >I\ t \ 4 lie h \ d 1 o. , 1 1 I hr, in car Ron hl;nks. hr n n m h e s r n n h I J : AO AO. ) 0 ,'J. o. I \ 1 K, II. I S 1 1 1 \ 1 . p, | ( . 0 1 1 >1 1 1 \ , S.; l'.i-.i si <iw , \ . ami I !ak 1 m K .: C a n i i m n im I n d m c a i R n n s a n d u l ai rd ( o m p o n n d s in p i o c r s s r d i nl i ne) . ( h n n e i /,Ys e n u h 1I; Am Adi. | 0 d | . A l e i i i i x . t'.. and ' i i m i o \\. Ma V.\pri imrni s in l ; idc n li 11 <a U< m . >1 ''>: I I>cn / p \ i m r in d o me s Iir soi l !>v me a n s oi i h r Iiiin i es. r i u r s p i i i i n m . h u t . /. (uni t <i A: 107 - 1fin. 1!) I1'. S. [ [ \ \ i \ 1 1 1 \ n , 1', ( , a n d i Imk \ . In. I h r tela l ion.si i ip In I\s eei i I m m a n s mo k i n g haRils a nd deal l i l ai r s; a h d u e u p s i n d \ o! I S7.7f.ii men. /. T Ai, Inn: l a i d i:ws. RIAI. A. l l i i r i u , M. ( : ( >m u pa Imi n t ! I l l i noi s a n d Allied Pisiases, s p i i1 1 p 11 e 11 1. Illinois, h i n n i e s h ! horn, is. Idl'd, in. I h i n i o W. h a I ' m i i o n m e n i a I inn;; n n u r r . h i , h i s t . M , d . 0 A//e- do- 10 'nl. I d ' T II. k i \ \ \ \ v \ Y . Id: I he st a Iof 11 a I si ni ilu a i n r of h ol o^ii ai dal a. I h il. A/. /. 'J: o d . IOn I. Id. kii 1 1 \ . I'.; I- \ i is. 11. 1 \l \M i:, Id. a nd 'I ii omas, V.: \unii.iUc In d i o< a i Rons. |, l Oe- ai ne in tin law At I S AiiLMdes a h n o s p R e i e a nd i h r i a u i l i ndenu iI\ ol ai mm p h r i i< r \ 11 a< Is. . /. Al . . {. / u i t. I n d u s ! . 11 v.1.;. 0: 1 iA IhA 10'. t. im , 1' I;, i 10. knii.N. id: 1' Uk. II. I... a n d I m a n s M.: Ai" m.iiii li \ d i o. a i Ron-- II. I R r s e i u r in llir p a i i i o d a t ' p ha s e ol ir i snRnr e n n i u r r shausl . s a nd i h r o m ino^rnii il\ r,| ev h a u s l eMiact.s. . 1. M . . 1 . . l ul l . I n d u s ! . / / \ d . 0: In i 177. Iddl. I !. 10 au ie I h u m Si r\ h i . D n a k i m i m ei Hi \i i h , ] ih i \ n o \ , a m i \Vi i i \Ki : \ ' i i a l Sl alislirs ol i h r I 'niloR Si al rs !0n0; X' cdmnr III. Woi t al i l v Dal a. Wdisliinnli'ir . I).( . ( . o M ' i n n u n t i d i n l i n g Oilirte Idnld il, H i l l ), M.isnc,,.. 0 a, t.R'O! | ; Id. 10 ui ie Iti u . n i S\ rvii e h m i n i . S n u a i v Ar m i a : ( n i K i a M o i R i d i u Sri irs. I 10 (I' uRl u I R u l i h Srn i . r I'n R| . N'o. I",, (id. i-7, 1 Id. IdO, I AL?. 17. dl . dl 7, J t i 1 Wa s h i n g t o n . !).('. ( . m n i i i i i n i i i On i l i n r (Mlnr. lOA' I Odd. K> s i i i .m k . Id I.: l.iiolouical im pli< a t nm-. ol ilu ` ^ro<;i aphi r. i | >lisn i Im i ion ol h i n ^ e i n c r i , . t i ' n , (diion n i l i ' i n o t . i o n i t e ( i n n e r 0: 1 ><) i 7 >. lO.Vd ,n IS.M 'm l 1>rn ' IiI i n i\ : 17. Si i i n u, Id U n m a n s i ^ n d n a n t r ol e s pr i t : menial i a u inoni nrsjs. A/. . 1. . h < h . ' nt h. nd; d_d dl I. IOdd. IS S 1 1 i m it. Id Id: I h r ( <>nd il ional Riolo^ic a I a< Ii\ il' ol ( h r <ai r i noi ; r us in ( a i Ro n blacks, a i u i its r l i mi i Ui Mon. ( ai u r e r Hr s e m ( h II: 10 AI I(). 1On I. nui ",i.n -''li.,: ih-.ii nm: 10. S 1 1 ini io Id 1.. a n d t UK. I i . 1 .: Su m ma l ion a no, i uhi Ri Uou r d r r ( s of weak a n d slroip; c;\u iiu.i;rni< hv d me a i hoiis: I .d Im n / a n l hi u cmr, i hi vsenc. I ddsdOecii : l i r n / a n l h i a f r n r . a n d d0-met hv l<In danl In r n r . ( hi nr c ' Ih'-Sf n u l l I I: n0 01'., IOn I . dO. S h i m io Id l-d: s i w m o D. \ \ .. an,I Hni YU'i'o M. N.: A s r a i f h Im ( a u i n o ^ r n i r subs t ances in i a u i n " ma l mi s h u m. i n l n n u . I x h . I 'n t l e 'id: dOOnol, 1017. dl . W m .i .i.h, R. I'..' I lie l ) rn/ | >vrenr r o n i r n l nl town,; air. / h i t . J . ( h n n r i (>: S d l , I9dd. JO , , mi,l .in. , da.- tr;n : i ; < . IMOI , me; i U i )I in , 'll;, i s , ; Mu,. f: In- . l; `.I il 1 , p rum; p. id. e" It. h" M as- in