Tobacco Documents Online

03. 1T'9,~ TUE 13 45 FA~ ................. :},(--~*z> ~)..~:>.~,~ [4~01)9 May I~. 19~0 L A. Cause or Cau~e~ Positions/Questions OutlLne No ont know~ the cause ar causes of lung camcqr. C. Multifactorial Disease Studies zeport I~g cancer to be statixtic~.lly .~ociated ~a~tor~ ~cl~di~g r~ce, ,t~icity, religion, sex, on.potion, ~i~t, Epidemlalogict/Evi~.~ce Stu~i~a r~pozt ~ statl~tica/ a_,ao¢iatlot~ ~ztwt~ smo~g ~d l=g c~¢~. Howevtr, ~tatistlc~ studies ~o nat estab~h a causzl relationship. Rath~ ~7 yo~t ~ t~ nte~ for c~ntc~ ~4 labo~tory re~=~ in o~er to determ~e ~e prec~e.relation~hip- Cau,ation v~. the Constitutional Hy~othe~s The reported ~atlstical association between smoking amcl lung c.;mcer ~ ~etter e~lained by a constituti~l or genetic h~ot~esis (i.e., the smoker ~d not the smoking Is ~espon~ible for the a~ociattoa) ~ by the cig~ette ¢ausation h~othesi*- C. Methodological Weakx~e~ses i~ Prospective Studies The subjects Ln prospective stu4ies ~-e sell.elected a~ to smo~g, 1-,-, the subjects decide for themszh'es whether or. /[~/~ not to smoke. Accordingly~ re~I~s of ~ch'ttud~cs ~o not elimiuate the constitutional or gtnetic h~othesi~ (*¢e above}. -1-

03,'i7 98 TUE 13:45 FAX ~)~ only ~mo~u~ rather t~-multifactorial [i.e., examining the Unxepre~mo tat ire tire of ~t gener~ population. Far example, iB Hammond'a U.~. populattom Mcthodologi¢~ WeakB~r.~m~ G-t IZetro~pective Studies b. Co~y mad C~ Compa,r~o~, Dif£erenc~ ia lung ca-~cer mott~3.it~ in v~Jou~ p~t, of corruption. ~e~ diff~en~e~ h~ve be~ shown to exit f~ co~t7 to co~ty~ from ~it~ to ~i~ ~d even withi~ ¢itie~ ~acial ~i~crep~clea Difference~ in lung'¢~cer mortality betwee-B whltet black~ c~not be explained on the ba~i~ of ~g~et~e con~ump- t~a H-e., blac~ smoke fewer Cig~ctte* ~ white~ but have hi~her lun~ ~nccr mortality). .7_O

So Lung l~',~Hgious Disc~ep~cies DiE[erences in the ~cide~ce 0£ I~mg c~ncer between Se,=ish a.nd non-$e~ish popul*tions in Montreal, Pitt~b~h ~d else- where c~not be e~lained o~ the b~sls o[ ~t~e ca~sump- tio~ M=le-Fe~ale Discrep~.ncies For many years there has been a wide difference (&:l} ~-~ the incidence of lung c~ncer mortRlity ~n males c0~pare~to ~em~ R=cen~ studies report ~ ~e ~ r~tio is d~cre~- ~g duc to ~ p~k~g ~ ~e ~ence of I~ c~c~r ~mo~g ~a]~ ~d ~ concomit~t ~e~se ~ [c~e~ However, ~e reported ~crease amoog fem~ ~ l~gel7 adenoc~c~oma, a t~e of c~cer fo~'~ studies not to be se~t~H~lly a~ocl- azed w;~ smok~g. ~ermcre, studies ~ the U.X. ~d that the m~Ie-~em~e I~g c~cer ~d c~g~et~e con~tio~ ~t- cau~ti~ h~oche~s. Occup,tion -axious occupations ~¢hie.~ ~e not explained by Y~ zhe e~'ly t960°s ,~ese~xc.l~v~ examin?d the lung cz~cer dea~ rates ~rom ~e 193D~ t~ough ~e 1950s ~d to~d k~ea~ but at ~ ~~g ~t~ ~ ~ ~t, they pr~dict~/I~ ~ 7 next decade ~ ~ ~o~ ~ ~he ~.S. ~ ~e U.~),.reach~g the~/ S~ud~e~ s~ce th~ h~ve ~pport~d the~ pre~ct~ (Le.~ ~e ~-~ d~ce of l~ c~cer ~ the U.K- h~ peter ~d ~c:e~g ~ly ~ ~e oM=st age ~s}- ~e c~r am~ ~.S~ [em~es is ~eported to be ~cre~s~ but the ~ __ t~e o~ I~ c~cer ~e~ ~e ~yorte~y de-elop~ (i.e., adenoc~- c~om~ ~ ~ t~ o[ c~cer fo~d ~n s~ud~es not to be Real versus Art~/act Ma.,~y scientists h~ve obse.~,,ed that the l~g cancer migh~ ~e]l bc due to increased diagnostic ac- c~acy. ~e probl~m ~ comported by early p~t of ~e cent~y ~ere w~ pro~abl probabIy ~ tendency to o~crd;~gnose

03/17,9~ TUE t3 45 FAX Ad,,a.'aces in Diagnostic Technique~ The principal techniques for diagnosing lt~ng ca-ricer ray, bronchoscopy and tputum cytology} became widely available after 1930. ~ere was ~ot e~en a ~ecific I.C.D. category for l~g c~cer ~til 1939. Accord~gly, at~emp~ to comp~e l~g cancer ~ the ¢~ly century with l~ng c~ccr today ~e often mislead~g. Inaccuracy of Death Certificates Studies of smoking and lu~ng c.a.ncer often raly upo~ death terrific:ties in determL~ing cause of death- How~ver~ m~T studies have fo~ death certificat~ to h~ p~tic- of deat~ Confusion with Other IRe~-piratorT Conditions ~ o~Iy a small pert=hinge (i-e., about 1-5~) of ca~es ' ~agnased ~s tub~los~ ~ othar ~fectlous ~ea~es ~t app~c~t ~crcas¢ ~ l~g c~c~= ~ce ~e tu~ of the ce~y ~ould h~ virtu~y aliminzte~ d. De~,ection Bias smogars in e~ua~g ~ medic~ situation, smok~g the ~se~e itself. ~onfusion of Primary a~d Seconda_~/ Studies Fred that ~he main re,son Jar d~ath certificate ~nac~a~ wi~ r~g~ to l~g ~cer is due to ~e inabili~ to dist~Is~ prim~ l~g c~c~ (Le-, l~g c~c~ whi~ ~es ~ ~s lung, ~rom secon~7 ¢~cer (Le.~ cance~ whi~ m~t~st~izcs to ~e I~E)- M~y of the met~tatiC l~g c~cars ~e from ~s not even statistically associated ~i~ smok~g. Population quali~ies Age this cent~'-y has rcs~ited in ~ older population ~oday. perhaps ~tth ~eaker l~gs, which is p~ticularly ~sctpt- ible ta ~r~nic pulm~n~7 disease~, such as lung c~cer. Furthermore, ~tudias, of c~cer ~ diHtr~nt countries age ~t~ctur¢ of the populations f~d that the total number of ¢~cer deaths ~ a given population is relate~ to its age armature not its environment. 2S2023470

03 17 !}8 Tug 13 ~8 FAX . [~,I b. ~ohort F[l'ect ¢~ncer ~ ~llke other a~er -- d~d Aot ~orrelate ~ith ~c~ea~ing age but ra~her it peaked in ~hite ~ale~ ~ the latter half of t~e ~i~ decade of li[e. ~ey lh~ ~nding to a ~eeable ¢ohor~ o£ men ~i.e., ~hose born a~d the ~urn of ~e certify} ~d postulated ~ this vu~er~ble cohort grows older ~d is elim~ted frnm the ~opulations ~e incidence of l~g c~ccr among ~hlte ~a1~a wo~ peak ~4 £ina~y decline. s~udiea conf~m ~he accuracy of their predlction~ (i-e., in the U.S. l~g c~cer ~ ~cre~s~g ~Iy in the ctdes~ catego~ ~d ~ ~he U.K. it h~ peaked. ~al the age vf incidence of l~g c~cer dae~ ho~ ~epend eider up~ the age at ~hi~ =mo~g ¢~mmenced o~ the duration ~f smok~g or evea ~hether or not one smokes. The claSm t, ha.t smokes ~ho ~ale ~e more ~hle co c~c~ is ~¢~n~tent ~i~ ~ ~dings from one pro~e~ive Ce~ati~ of Smoking W'aile most a~ll-smoker~ c/aim zhgt a~ ~x-~moker°s rL~k for developing l~g c~cer ~pproa~ ~at of a .nonsmok~ y~s after ce~ation, at ]tgst one claim~ ~at ~ ex~oker's r~sk for deve~op~g I~E c~cer ix ~onsi~tant with the constitutional 4. "Tar" Yields The peaking of lung cancer in ~hite ~ales /s more llke]y the re~lt of ~e ch~ng ~at~e~ ~f the ~seate ~h~ ~e decrease in "tar" yields of cig~etta~ during ~e last ]5 years. ~ the c~ly 1960's rese~chers excreted the l~g cancer death rates from ~he 1930's ~hrough xhe 1950's ~ fo~d ~em t~ be ~crea~g, hut at • decreasiag rate. As a result, they predicted that the male death rate f~m I~g c~er ~ould level ~ff in ~he nex~ decade or so ~h0th ~ the U.S. ~4 the U.K.}, r~achtug thclr conclusion ~ithout r~g~d to lh~ ~ok~g h~hits in the population- -5- 2023 ? 1

03/17/98 TUE 1.3 46 FAX ~x-p ~im ent al Igvideace A. Anim:al Studies I. Lung Ca:acer and Laboratory Anim~Is Despite a~ enorraoua research effort to produce i~ the • ted with smokey, resear~cr~ have fa~,d to produce a. Beagle Dogs Several yea.rs ago a researcher cla.i--c~l ~hxt he had~ produced I~E c~cer ~ heagl~ dog~ e~osed to ~resh, whol~ ~moke. ~s e~er~ment received a grc~t de~ of rese~ ~d a great de~ of trouble ~d~g a scienti- fic jo~al ~at ~Id p~b~ ~e ~ud7 be~e hi~ con~l ~ ~d other ~e~od~ogles w~e ~ade- "e~l7 ~mo~ ce~ bron~ c~c~om~," but h~ pi~ t~ o£ ~e~ ~ppoaedl7 ~x~ve ~i~a do not ~ow eider ~c~oma, or ~v~ion~ ~ ~y .evenh ~e re- se~er's ~m ~at he hxs p~uced ~ dogs ~ t~e o£ l~g c~cer ~at ki~ hum~ has ho~ me~ ~i~ ~cre~-J ~g s~epti~sm ~d =ou-accept~c~ Some of his dogs~ ~o~ ~ose4 to smoke ~d ~t ~ ~po~ did have statistica~g ~oclated wi~ smokey. ~stead, ~ey ~e hellevad ~ he ~e re~lt of • ~1 ettvlo~. b. SF~i~ Golden Hamsters Syrian Gold~.~ hamsters have bee= • populaz model ",.he experimental produc*.ion of lung cancer hacause their l,r.~o~n capability to develop *.he disease cape:sad to a cancer causi~ agent. Nevertheless, se~chera ~ve ~fformly ~ailed ~o produce ~ h~msters expose~ to gze~, ~hole cig.are~te ~mokc the k~d ~ ,c~ce~ reporte~ to be stat~tically a~ociated ~ith ing. One life time study reported ~at h~scers to ~woke gained le~ ~eight th~ the non-exposed ~als; ho~e~er, ~he expo~e~.~nimal~ lived longer non~xposed controlg -6- 2S2023472

03 ~7 9~ TUE 13 " 46 FAX. ~nd Other ~odents ~e~plte ~n ~normoua research eIfoct, labocatory tests ~ole ~m~ke h~ve tailed t~ produc~ the ~d o~ lung ~7 c~cer reported to he atati~ticall~ a~cfat~d ~t~ amok- ~g. ~d, ode ~cent ~p~imc:% whi~ ~xam~e~ ~e potengi~l of tobacco smoke to act with other chemlc~s~ ~lu~c~ atther ~ fncidenc~ ~r ~e la~ea~ of I~io~s ind¢ced ~ mic~ -ith a laharator~ carc~o~e~. c~cer on the skis o~ ~im~s p~nt~d with tub~cco smoke ~lav~ t~ ~e ~m~ l~g ~c~ ~rob]em- Am~g ~e re~o~s given £or ~hi$ ~iew ar~: . The rel;zttvely enocmoua closes o~ ":ax" used. skb-, painting experimenLs. l~mg tLs~e, i~r..hadLng va~ima~ cle~ct~g mee.hma- frex~ ~hcle ~g~ette ~o~., ~~ers have reported ~e p~ductio= of l~ge~ c~c~ ~ h~msters ~ose~ 10 to~co ~oke; hc~ev~, h~ ca~e of ~e pe~li~ ~hy~olo~ O~ ~e hamster (l.e., it conc~trates ~e ~moke on a sma~ ~a ~ sk~ p~L~g th~ t~al~on te~ The posslble role of v|ral agents in sk/n paint/ha ~ ~ Other Tachniques ~Impla.~tation, I~.srtLlati~m, etc.) ~l-~ents or in special media such as w~m bees ~, tmpl~t~- tion phlle~s, ~c. Some researchers have claimc~ poaitSve~ results; ocher expcrlmentx ha~e resulted ~ negative findings -7-

TUE 13- ~6 but, unfort~'aately, little ~ttent|on h~ been paid to them. example, one such study found that condensate the trachea of test ~imals did not re.It ~ ~y c~cers of the tory c~cinoge~ c~cer~ ~ese ~trapolat~g the ef[ects B. I~ Vitro Studies Some studies have reported mutatioual b~ct~ ~d ti~ue c~turex e~se~ to tobacco smok~ condensate ["t~") ~ tobacco ~moke. How~, no one ~d~t~ ~e ti~e ~imal ~ari~, not ~ a ~b~titute 7/ C. Ca.rcinogeno~is The 1963 Su.rge~n General'~ I~.=port tobacco smoke t~ ~e~t a ~zzlin~ ~om~." ~l~ewh~e, ~9~ ~port .a~o~l~ge ~e compl~ n~ o£ c~og~asis.~ e~og~ ~ ~Z~ette smoko ~ too 'sm~ c~c~og~ic ac21vi~" ~ ~be~ed ~ ~e~ ~ gig~tlc ~roblem m~ ~d, ~ 1977 ~ U.S. D~m~z of Health bootee ~tlt1~& e~p~ment~ tobacco smoke c~og~es~ "~at ~us~ relatlon~hlp becwe~ ~ig~eCte xmok~g ~d c~¢e~ h~ he~ dcm~at~'" ~e booklet [~ ~dlcated that i~en/~cati~ O~ ~it~a~ ~d ~romotcr~ O~ ¢~cer [~ tobacco ~t~ficial to focu~ upon th* effecta o[ ~y one ~gredien~ or J ~t~up ~ ingredients ~ i~ola~io~ from the other~. It N~ loag~ ' ~ ~¢cn ~o~n, /or exampl% that certain smoke constituent~ a~t~ 7 */ 7~ ~ ~ti-c~c~ogen~ ~ test ~imals. Similarly, co~po~ds th~t~ ~e c~c~ogeni~ i~ test ~{mals, ~hen ~plled in i~ol,~ion,~ 7~-- -8- 2 2023474

03/17 TUE 1347 FA.~ smoke previously thought ~= he ]xck~g ~lIogether genlc ~C~ivi[T have t~ce~II~ ~e~n (o~d to be geni~ ~hen ~pplied with true ca~cinoge=~ ~ test product ~t is produced bg pas~g tobacco sma~e ~tly, stgdles sho~ that there ~e qu~tative, f~esh smoke ~o ~hich hum~s ~e ~osed. Tobacco smoke is a. h~ghly coml~la= m~x~u~e o~ so-oral thou- tobzcco smoke does contx~ ~ m~tc amo~ o( ben:o(~-~ ~7 p~r~e, it d~e~ no~ me~ tha~ It ~i~ be h~mE~ to th~ ~moke..J ~of~ .w~ sgu~y showed that ~ofers e~ed m conce~-~ e~o~ in~ed hy smokhg had ~o ~c~sed ~cld~ca o~ ~g e~cer. 4. Nit~oaxmi~s ni~samiaes to be present ~ cfg~cce smoke. Other studies c~¢et. However, scientists ~d goverum~ agencia~ g~-~ c~cer rem~s unde t~m~e~ ~ A. Cl/nica! Evldcttce -9-

03/17.'98 TUE 13:,17 FAX r~lq. Persons who have never smoked develop camcer of the lung Studies indic~te that a substantia.l number of lumg co.ricers ragi~ ~hich i~ the place ~ thn ~ most ~ose~ to tobacco though the trachea, ~hi~ i~ p~t of th~ respiratory more exposed to tobacco smoke t~ the Laryngeal Cancer Although the l~ynx, which ig p~.rt o~ l~eal c~c~ h~s remained Second l~:im azie_~ ~ILhough Lh~ce is no reach to ~ppos~ ~t there ~ a grea~ar ~po~e La tobacco ~make. at ~he site of ~7 giv~ l~g c~cer l~g~ ~ ex~emely rar~ c~cer ~d others ~ not. ~se who hold studies by gellerm~ ~d Sh~ ~hi~ reported ~t p~centage o~ ]~g ~cer patients had high level~ of ~d~cibil-) i~ of ~ ~zyme called ~yl hy~oc~bon Howcv~, more recently Dr. Shaw has reported that he could ~ot rep~cat~ his e~lier find~g~. ~ere is ~so puhllah~d~ c~£i¢~m of the Kell,rm~ ~ Sha~ study ~eai~at~g tha~ :he of the mitogen use~ Other researches ha~e r~orted production of ~amou~ cell l~g cancer ~imals, a ~ding which ~z conteg~y to the ~ech~is~ ~her~by ]~g cancer is -10-

03.17/98 TUE 1317 FAX t Autopsy 5tudie:~ ('P~o-ma~igna-nt Cha-nites'} Some researchers ha,,e reported from autapsy studies thal stz~okerl questions as to the relationship of ~uch thegns to hum~ c~er. as mell as whether such chokes ~¢ rela~cd to smok~g. No ~ne h~ demonstrated that ~ch ch~ges progrea~ ~to ~nv~ive e~cers or ~h~t ~e7 ~e ~ e~e~tial ~tep ~ the devalopment cer~ ~dicate that they ¢111 occ~{onally rem~ stable for ye~¢ or ~grc~ ~d di~a~pe~ ent~=ly even ~ithout tr~a~menL~ ~ece~tly a study ~ r~ported a m~re th~ lO-~old decre~e ~ the ]~g~ ~crease ra~h~r th~ a comp~ab~e d~cre~ ~ ~a reported ~c~d~c~ of l~g c~cer, ra~e fgrthe~ ~ue~ions k~ut ~he rel~ Histological r~le~ed to as G~p ~ tumo~ ~o~e ~ho ~o~ ~s thco~ contend ~e~ ~ l~ c~cer~ w~ ~ue to ~ r~e in ~enoc~c~oma~ ~amo~ c~ c~c~oma~ 3ut later ~mc ~tiata (i,e-, ~ua~ua cell ;~c~omt~ bet not Group ~ tumor~ (i-e., adenoc~- numb~ o~ squamous cell c~c~o~as berg report~ L~at ~ges ~ ~e prodacx (i.e., ~e addition of ~lters, etc,) haue been S~geom Gener~'s report, as ~c~ as some other re~¢~r~r~ that t~ reported increase of l~g cancer ~ women not gener~ly a~c~ce~ ~ith

---

03/17/88 TUE 1343 i " " 2~) U.S. Department of He~l~h,. Education, an4 :¢elgare,. Th.e Heal:k" Consequences of Smok~Ag: 1@68 Supplement. pp. fl9-i17. 29) U.S- Department" of Heal:h, ~duc~t~on, 'an~ Nelf~re, Smoki~,~n~ Health: ~eport of the Adviso~'Committee ~o ~he SurKeon G=nmral o£ :he Public Hea!~h betas, p.l&l; ig64.

~'6 tI

---

P.17/2~

87. Be.rksea,J. S~oki~g and cancer of the lung. l~la~o Cli~ Proc 367-385; 1960. 00.9,2.7 8B. Berkson, J. Mor~ali~ an~ marital s~tus: Ref!ec~ion~ on'the derivation of e%iolog~ from s~a~is~ics. ~er./ Public Health 5Z 89. Berkb~n, J. Smoking' and~n~ cancer. ~led P:oc lS" 327-~36; !964. ~ferenee to lung cancel J 5o¢ Occup Med 25(I): 2-10: 1975. ~9 ~ 91. Fish,r; R.A. Dangers of cig~re~ze-smokin~ " Bri= ble4 J 21503g]: 297-298; 19~7. 2 92. F~sher, ~.A. Ciggre~tes, can~r,-and s[a~iatics- CenZennial 93. Fi~h~r, R.A. Lung cancer and cigarettes? Na[u're IS2.Cq6Z$) : 108; 1958. ~ ~ TM 94." Fishe~ R.A." Smoking" Tie"Cancer ControverszL ionaon: Oliver 95. RiEdon, R.H. Cigaret:e smoking and lung' cancer: A "- of t~is rs!a£ionship. South~ Mcd J 6Z(Z): Z3Z=Z3~; 1969. 96. Rigdon, R.H. S~atement presented a~ Hearings before [he Committee on inters~a~e and Foreign C6mmerce Hous~ o~ Represcn~ntzvea, Aprll 97. Z~o~Iman, H.M. e~ ~i. , S~a~is~iis in medlca~ research: Principles versus practicos. J Lab Clin ~ei 71<3)" 357-367; 1968.. ' Selzzer, C.C. An evaluation of the ~ffec: of s~oking on corona '} hear[ disease. J~ 203(3): I93-Z00;!96S. /59~ " 99. Yerushalmy, I. On inferring causality from observed associa£ions-. in Controversy in .Internal Hcdicine, ~.J. In~elfin~cr, A.S. ~clman, H., ~n'ian4 (ed~_). ~h~. 5aunder5 Co. ; 1966. pp.

196~; Report tha~ "~atlstical methods cannot es~abllsh 9rcof of a causal relationship in ah association." The .Oyervie~.~ also ignores t)~e obsc~-vation in tho 1964 Re~ort cluslun~. The~ep6rt =onslst~n~ly ignores, when referring to statistical associations, the importan~ scientific prin- ciple ~hat such associa~ion~ canno~ establish causal re- latlonshi~s.13-2N Even the 196g U. S. Surgeon General's port state~ that."s~atlstlcal methods cannot' establish proof | of a causal'relationship in an as~ociatlon.''26 U.S. Public Health Servlce= • Smokln~ and health. Re- port of the Advisory Co~ttem to the Sure,on General of the Public H~alth Service. W~sh~Kton, U.S. Depmmt-.. men~ of Health, Education, and Well,e, Public Health " Service ~ublica~ion No. 1103, I~6~. 387 9P- p. 20. ': Lance~ 2(8097): 978; November 4, 1978. The anomally that-'------Qouldn't go away.

03,17/98 TUE L3:49 FAX Ko£1er, S. ,.P~ssible Statements- Concerning Questions of -" stacis~ical'Cau~al Research. blet'rika 17(0):. 30-42; 1971. " BUr~, p.R.j.,.s Bees Smoking Cause Lung C~car? New Scient'is~ 61{88~9: 458-461, ¢65; 1974. ~ ~£~77 .. ~isher, ~nald A.', Lung C~cer ~a Ciga~ttes7 Natur~ 108; July IZ,..19S8. ~2X~I/ .. Bro~lee, ~.A., A Review off"[Smoking ~d Health"- ~scc 60CSll)" 722-739; 1965. Fisher, Ronald A., Smokin$: ~e C~cer ContrOversy- Oliver ~6 Boyd; 19S9. BSX'ch, P.R-ff. "Smoking and lunE cancer: the-problem of £n- £erri~E cause". Journal of the RoT~Z 3~a~'~s~Ical Soclet~, Series A, 141(P~ ~)? ~37~g77; 197~- ~age C~mmit~ee on Health, Welfare and Social Af'fairs, Hearin9, 28th ~azliamene, Ise Sess., May I~, 1969 (Ottawa,. ~he Queen's ~rineer, 19~9), pp. 1058-1078, - Dijkst~a, B. m king and Lung Cancer," Suid- Afrikaanse Kankerbu!latin 2313] : 87-109, Eysenck, H.~. ~"ne 'causes and effects of smoking- Beverly H!IIs, Call£o~n!a: 5age ~u~llcat$ons; 1981..

03. I7/98 TUE I3:49 FAX h- XISSEN, O. M. The Presen~ Status of Psychosomatic Cancer Research. Ger£aZrics ~: 129-37 t'1969}. a. PARNELL, R. W_ Smok:in~ and c~ncer_ b. DAMON, A. Constitution ~nd smoking. r-anc~t l: 96~ C£9S1}. Science 13~: 339 ~L951~ 93. ~urch, P. R.J. Smoking =,d health. Lancet 2(7768): 132-133; 1972. 95. 96. , 97. flu;oh. P.R.J. Smoking and hoalth. Lance____~r2(7792]: 142]-1424: 1972. Dutch. P.R.]. Smoking and c.onccr. Lancet 1(75t'}9): 939-940; 1973. Buzch, P.R.J.'Smoking=nd cancer, Lancet f(7815): 131S-1316; 1973. 1lurch, P. R, J. Smoking and cancer. Lancc~ 2(7820}: 102-1'03; 1973/ -7- c~,~~ 282023486

03. 17 9~; rUE 1350 FAX 98. 0urch. P.R.J. Does sn~okinl., ca*,sc It, ng c~cev7 NewScie,tisc 6l(gg6}: ,t5,~-'163: i974. 99. fhJzch, P. R.J. Smoking and cancc:. New Scicn{Is~ 61(891}: 6]7; 197~. I0~. ~urch, P.R.J. ~mokingnnd cancer. New$cle||tlst ~a(S92}: 4h 1974. I01. 13urch, P.R.I_ SmskIng and cancer. New_.Scientisc ~2(895): 195: 197~. 1~2. guzcl~, P. R. ]. ' Smoking and cance~. New Scientist ~2(~99): 503-50~: 1974. 103. Butch. F. R.J. $~oklng and lung cnncer. Lance[ 2(TgSa): 950; 1.974. Bu~ch, P.R.]. Smoking and lung c~ncc=: gulch's reply. NmvSclends~ 6!(887): 859- 560; 1974. [lurch, P. R: J. Problems {n tl~e int~:~rcratian o[ cancer statistics with =~rcrcncc ~o lung cancer. ~ Soc OccuJ_~ Med 25: 2-10: 1975, 105. ~uzch, P.R.J. Par~ Prcss, 1976. sot ~urch, ~hc zmoR~ng and lun~ canca~ m~rtalltydata in ~ri~ain are more cDnsistent with ~he co,~stltutional hM- l~O~esis E!~s~ pos~ula£ed, by.Sir Ron~d 91sheP In 107. F|sher," R. A. 1~. Fisher, R.A." J09. ~shcr. R.A. ]SI-J66; J 9S~1. The B i01,,~u,'," of Cmcer: .~t ne.w apl~roach. [ialtim~re. Rid. : Un{versi~/ !ii. • the i950'g Dangers o[ c[ghrer~c-smoking. Tlric M=d ~.2(50.39): 297729S: 19S7.. Lung cancer and cigarettes? ~ur~ 182(462~): lOS; I95R. C;gnrct~cs. cancor, and.~t~tisdcs. C~ntennial ~evAvtsSc{ 2: Fisher, R.A." Lung ~ncsr and c[~re~es.? ~ur~182(4628): 10~; 1958. F~her, R.,A. ~mo~i$~ ~e ~occr Conerover~. London: Oliver & ~oyd; pp. 7-47.

03, 17 98 TUE 13 : So studies sugge~E-that there is a.ge~e~ic pzedispcslZion to " , . i12 71~6 s~o:<xnZ. Aloo of interest ar~:th~ atudies sbo~:in~ that smo.,In~ habit--. ii2) Fisher, R.A. ,. Cancer and. Smoki.ng- Nat~re 18Z: 5~6"; August.~0 1958. '. 1!5) Rz~scho~i-Nielsen, E., S=okigg Habits in ~ins. D~ish 7[~>: 82-88; 19~0. 277-284] 1972_ llS) ~herg, L. et al., Smoking Habits 0£ ManoZygazic ~d " Fisher, R.A., zt al-, L~g Ca'nc:f ~n~ C$~ar~s~ Na~urg [46Z~): 108; 1958. 117) Co~', ~[W., Personality Variables ~soci~ea l~i~ 86-i0¢; 197~. 118) Sel~zer, C.C., I-Io~holo~ic~! Constitution E~iron Health 17:[ 14S-147; J-~y,. i!9) Bro~,~, B_~.~ Som~ Ch~c~eristic ~G Dif~erehdes Bet~¢een Smoker ~ N~n-~oker Subjects. NeuroDsz~olo~ia~6" 1 .1968. 12~) Seltzer, C,C.,'Can~tizu~ion and H~re~ity in Relation to 142: ~22-530; 1967. S~okin~, Inhalation ~na- Personality." B~i'~ 203-Z16; 196¢. iZ2) seltzer, C,C., Occupation rand SmoI~ing in College Gra~uates- _J Appl Psy.-chol 4S[I): I-5- l~fi~. " 123) Kissen, O_M_ Personality mnd hmg Cancer. Uan'c'e~ pp_ Z16-217~ Janua_~y 25, i964. 124) E),se~xck, H:J.-, Smokers an~ Wonsmokers. Chap. S Smokin_~, Heal~h and Personali'-~- London: 1'lei4en~!d ~d Nicolson~'pp.flU- i0o.

03/17 TUE 13 5o FAS Claimed .~:~a~is~ical as.~ocla~1ons b~l;~.i~cn slnolcin.~ a:~d various dls~.~s, as ~:e}l as.overall ~orcall~, are ba~%cr ex~l~ined b~" a ~enetic hypo~hesl~ {l-e-, the. %ban by a ci~e~te-:~usa~lon hypothesis, lO0-~O~. re.eerence to lunZ ca~cev. ] S~c Occup Mcd 23(~): 2-10; 1975. 101_ Bd:ch, P.R.J. SmokLnE and lung cancer. Lanc~r'..~2(7SB6): 950; 1974. . : Lung cancer an~.ci~-',reCt~s? Nature I~Z(46ZS~: I0~; Cancer and smokinz. NaeCtre 1~214635]" 596.; Smoking.: ,The Cancer Conrrovcr~Z- London: aliver L=ncer i(7897~: 40-~,I: 1975. .. I05-106; 1975. Karvoncn, N., e~ al., Cigarette.smoking, serumocholcs~erol, pressure, ~ni 5-Ed~'-~atness: Observations in Finland. Lance: Selczc~. C. ~ Smokin~a~d cardiovascular disease. Ama~ Hear~ 1975. 109. q"homa_% C.B.. cral., PersonaliW characteristics 0£ medical s~'udencs as re~ececd :. Johns Nopklns k.l~) 127(0): 323-33&: 1970.

B~rch, P.R.J. "Smoking and funk cancsr: ~he problem ferrisK cause". Jo.urnal_of the. Royal ! Hills, Callforn~--~age ~u~eatlons : 19~d-l. • .

03 i7 '3,~ TIIE 13:~/, F.~X 1974.. 163. Friberz,. L.., et al., . .~lo_r~ali[y in ~wins in rela=ion to smoking habits and alcohol problems. Arch Environ Heal~h' 27(S] : 1973.

03/17/98 TUE 13:51 FA~. 164. Gordon, To, Kennel,. W. Hultiple contributors co coronary risk implicztion~ for ~crcening and prevention. J Chrcn Dis .25(I0-ii): $61-$65; November 197Z. 165.. Yerushalm[, J. Self-smlecti~n--A major problem in obse'rvazional stuaies, zn Procee~in'gs' of "t~'e' "6th Berkeley "5Zmposium on Ma~hematicS..~ Statistics and P[obabAl~ gol 4;'p~ ~2'92342, I~72. upon th~s/s~ud~ in the B~itish Medlcal'Journai, "~he tempor~l ifends ~'n overall show no co~istent association w%th trends of s~klng habits. Of course can be objected, with ~ustice, pointless to compare mortality ~ ~he selec~¢~ ~oup o~ ~oct~rs who chose ~h mort~lltM ~ ~he Kenerai m~le which differs In so'~ constitutional ~nvi~o~nt~ respects ~om the respondin~ doctors. "3~ 34. ~urch, P.R.3. SmoklnE and. health- . January 15, 1977. " Bri~- Ned. J. I: 165;

/0

0,3,17 98 TI,:E 13,52 frequ'ently ignored. --/5 ~ 282023494

03~17z9,S TUE 13.52 FA2 30. DONNAHOE, k. S. Statement Before the Commi~:~e on Ca~_rce, ~d Adve~is~_ $e=i~ 89-5, 1955. ~. i, ~. ~77. Z82023~5

03:17/98 TI!E 13:52 FA.~

03,~7/98 TUE 13:52 FA~ Su~. 199: Ill 7-19, ~l-W~, WS-~S, 57-59, lesea~ Council; 197~7 pp. t.S. C~unzries ~-~ ~19~6-1967)- dapanese Cancer 197Z. pp- 76, 77. ii0, iii. P,~s,~l~ 4dd" h.b " recent stmdy by Dr. Parka=h of lu.ng cancer remalned constant since I~62 despite the fact that tobaco.o consumption has been steadily inereasigg.79 .......... 7"9- Parka~h, O. Lung cancer: a atati~tical study based on " I autopsy data from 1928 to 19T2. ~..¢spiratlon 3~ : 29~- ,

03/17,9,S T[!E 13:$3 F.~X 1994 - 95 COLLECTION z zozo s A MISSING IN ALL SETS MTSS~NG I~ CLOSED AND ~.EV~4 SETS ( ) D~LET~D CHANGED TO ( ) DELVED A~D CH~GED TO USED C ~ } ADDED DATE OF CHA~G~:

---

---

03/17/98 1 L~5. a. DEAN, G.' The causes of death amom~ The South African- horn and ~i~rants ~o Sou~h Africa. So. African Meal. Journ. Vol_. ~9, Supp~ i C1£65) " On!o Int. Cont. Canc. i__~: 721-23 0_953). I~. EA$1COI~/, D. ;. The Epi#,~n~oloEM of L~ C~cer Z~a. i~et 1956 ~ : 37-39 ~9~69. ~.I~3- Dean, ~. L~g ~nc=r among ~Mtlce South A~r<cans~ Br~c Med ~" 2: 852-857; ;d14. 115. Dean, C. Lung. cancer among whlt,- SouzhAfric~ns: repor~ on a furrier s~udy.. B~c ~/ ' be~we~n zhe ~Lldi~no~ non-Maor~ pOl~tac£an and ~o~nl~nts/tom Crea= ~rlca~n. Dr[c ~mptCe Cancer Camp~l~ll (N. Z. ) Depn o~ H~]~, WeH[n~on. ~v Zealand, 1955. pp. ISg-llS. Eastco~c. D.F. , 37-39; 1956. The ep~demiolo~y of lung.ten'car in New Z~.~land'. Lancet TOTAL