Document 4JvMgBkeML9xKadZQ7d1YwwGj

i, PLAINTIFFS i EXHIBIT , 01-553. CD :? J" : j .. Asbestos Exposure, Smoking, and Neoplasia Irving J. Selikoff. MD: E. Cinker Hammond. SeD: and Jarob Churg, MD due to chance, the number of each deaths being right thnsa^npsr**)-** ham c>n< 1701 small. During the latter part of the study, we ob tained information on the mnkinp habits oi mout mm tram Jm I. IMS m April 30. IMS. Oi of the survivors, but we could not obtain reliable information on the habits of those who ,Tr:uriii'iiii.'S'ap --i had died at an earlier date. Therefore, we could not at.that time investigate death rates in rein* two to smoking habits and exposure to safaritos dost which were considered both separately and jointly. There is abundant evidence that cigarette smok ing leads to a high rate of death from lung fnr-f in the absence of occupational exposure to sshuli w dust.'' Our findings outlined above suggested < bat did not prove I that exposure to asbestos dust may lead to a high rate of dostb iron hing cgwr in the absence of cigarette smoking. If the latter be n 1964. we reported on death* occurring between I Jan 1, 1943. and Dec 31. 1962, among 632 members of the International Association of Heat and Frost Insulators and Asbestos Workers.' All - <we men had been occupationally exposed to so. then the combined effect of both types of ex posure might or might not be equal to or greater than the sum of the two effects On the other hand, it was possible that exposure t asbestos dust increases the nsk m lung cancer among cigarette aserc:^ . for many years. Their death rate trom lung cancer was found to be 6.8 times as high aa that reported for the general white male popu lation of the United Statea daring the samt yes .,. with age taken into consideration. Three of the men died at diffusa pleural mesothelioma and one died of a neopian histologically suggestive of peri- smokers but <)>* not lead to lunc iar.ar .among nonamokers The present study was undertaken primarily; (.. investigate these possibilities, '.u addition. wished to ohurn mors information on the occur rence of mesothelioma and gastrointestinal cancel ,irising asbestos workers toneei meaothahoma. Tina war- of interest since mcaotbeboma is a very rate disease in the general population bat t* reported to be associated with exposure to aaboatos dust.' In addition, their death rate from cancer of the stomach, colon, and rectum was higher then expected: but this may have been Fromjreconls of \ew York Local 12 ami Ns NJ. Local ;12 of the International Aaaomata Heat and Frost Insulaton and Asbestos Wo a Iact was made ol every man who was *_____ of mther one of these locals on Dec 31, iyi| I aaS chuff). tag Ok- ltap*'!- -a ho joined between that data and Dae U, No one was omitted ragaidfom of hfo Mm <r/. r at (to Bull-- I is work history. Ikawuwl data from aa l at e IIS* i r CM* Hi. Imm th M- IS i <t. of tits 632 on tbs unsat of tha men had Oat Mi ,, to asbestos dust prior tatttS.. *~',3V ir r PLAINTIFFS EXHIBIT f VvJV-C)0057| 01 043 0031 rSbl 370/ ,y....... npi--ema--jkPsamttwa--*i* --***.<*."* niywliibytteNi far aga atceding to tha aga < of tbe 47.5 expected deatha. T in Table 5. Expected vs Observed Dx -Aa dM--<taii Table a, tl--e wm 94 oha--a aatha (fe M oTtha 370 aabartoa workers died) an 47.5 deatha expected -- the hadeof the i deeth ratee of ell * in 196^n--.^thern w--eMr--mm 47A^46J 4M rhnpnir carcuinma. meeothein-- of tha pi--Ia time; peritoneal mesothelioma, we* rot tbe colon. four; cancer of the rectum, er ol the ati-rh, than; c--car of the , two; cancer of buocal cavity end pharynx, two; cancer of bladder, one; cancer of undeter mined priii--y site, two; adiratnaie, 15; cor pulmo--Ir, one; oomaiy heart diaeaas, 17; aaforthr heart failure. one; cerebral vascular lesson, two; aoroc aneurymn, one; cinhotre of the Hear, three; acote penenetttia. one; Wegener'* or-- and acrid--tel fall, one. Egpeete4 DexHtx-Far purporrr of -- wiahrd to aerrnain bow many of the 370 safe jecte would ham died during the 37 --with period (Jan 1,1968, to April 30,1987) U their aga-apedfic death catea bad bean exactly the smat far the grnaatl white male population of the United States. P#r thie purpoae. ueie nae of the United 8tatm 1964 Hfe table for white roama; thie provided tbe moat (table baaia far coarpenaen. It ba noted that for white raalae total death rate* and end rate* tram rmpimtory cancer were aiightly hir4*-*- r- *:. * industrial atatea of New York and \rw >-sar~ -n the United State* as a whole.*-' > `be other band, raepiiatory cancer daathmtee in wane ea-- aged 20 to 64 are reported to be a trifle lower than average laborers, not eiiewbtre ciaaaiflad erghgpd in conetrartion work.* Fm the hfa table wo determined for each of the 370 n--i the probability of hie dying within e pe riod at 52 mn--ha, conidering his age on Jen 1, 1963, and aawatnmg that tbe life table probability appletd to hta. Summing them pcobafcditMs lor tbe 370 men yialdari -- aatsnate of tba "expected" meat aa far United Stater white make The computeban indicated that 47.5 r'd ham ba-- expected, t, whfaad to aatnnata tba expected man- da --a ot tha pmcantage dfatiflmttnn of hf pq--of death ----g^fttted. 8tataa stomach. oofan, end rectum. Cancer of Lung, Pteun, and Trochee.-In petx- Krhari mortality data for tha United States show ing deaths each year from venous cruses by age, aax. and race, the fallowing diaaaom am combined: cancer of the hmg (including sot-- of tbe lung), cancer of the bronchus, cancer of the f-Hr* and cancer at the trachea. For thia group of rlianoaea. them warn 27 obeerved daatha and onfy 2.3 ex pected deaths, a ratio of needy 12 to L. It ie well known that, ter the United States aa a whole, aO except a vary tern ol the daatha re ported in the combined category are dm to broo- cbogenk caicinoma. Thna, it may ba ------>< that them wore dose to 2.3 mpertod deaths from this cause aa compared with 24 observed death*, a ratao of av 4Q to 1. Mesothiimma -Tea of the 94 afaaarvod deaths were due to meaothehoaa, thna worn duo to pleural mesothelioma, and ear-- went dm to pan- to--el mronthrlirwnm This is that if the 370 subiecta had random sample (ram the general population, ono would not have expected any of tham to the of mini tails mi* within a period of 52 All three of the men who died of plrmel th-iioma bad a history of regular cigamtee Of tbe seven who died of peritoneal one never smoked regularly, one smoked only ; a'*i - 'js... ju:a nv had a history of regi far rvtte smoking. Cancer of Stomacti, Colon, end Aorta*.--la our 1 earlier study of asbestos workers, them 1 deatha than expected from cancer of the i colon, and rectum 19b sipacted. 29 i compared with a total af LA them causae, than warn flight thia study, dae to can-- of stomach, three: colon, foot; n though thie beam out ear anrtii bar of deaths from these conei we still refrain from dwibg thia time. . ^ if 94 deaths. WhOt it it --I from this dwaaaa ocoer an [oi 043 0036 ,'.r"-V':' OKKUM-4CU1WV CT At 107 the bw*1923 aad the IM. All of tfaMo no ncetMtallr ttwagfa Doe 31, 9i 282 of then mod to hovo died 19 t *08 time. Of the r to ttt 20th of tfao bob'a as 4*44 4*44 M4 MM ms* 940 mm 7%-n mm TMM iClaastfM by Areata* Jsal. 1961. aad by TOM From First ( Exposure to AtkortM Cmw uo to Jsa 1,1963 1W. t U MM MM mm 49 4M m a 61 ' MM 2 12 17 . . ... *f hMltto not wmnmit mm M mm mm 4*44 .. 2 T 2U . 1 00 2$ ... 1 10 94 M 1 9n It 1 10 M ..... - 9 It I l 4*40 ...... 1 10 0 9 1 90+ ... t 17 19 2 l9 SI in M 9 9 9 ua* ... i t 10 n 10 17 0 8 9 34 |dsst and 255 occurred tfao 20th annnrer* That, of the 632 TsOW 2.--Satpets CtmsHM by Age ate by Smettng HaMta on or telart Jan 1.1963 370 were atill living : Jan 1, 1963. "hoee 370 men were mis i Omt oufaiecti of tfao preo; invmiigslinn Table l tfaeir OKO distribo- ao of Jon 1, 1963, 1 tfao lapsed time (nm wpiem) up to that I7N01I+yr fmf All of them km trarari, and 94 of area* famd to have il967. ' tfao four-year i iateraal h Jam 1,1963, to Apt in October l?b2, mi Hue OCT--riy --hw4 one to nine dgutte a day, 17 amohari 10 to 19 cigarettes a day, 97 amokad 20 to 39 cigarettes a to examine them man day, and 63 wanted 40 or more rigaivtrae a day. ax to tediv --i--dm tetas ge and physical aowdrttou. The cheat x-ray films ae anB aa Tfae --othf habits of the 370 subjects were compared with the smoking habits of s large num M- ber of ram swifted from the general population.' weal cumpiainta. Aihitether, There were proportionally more cigarette smokers among the 370 subjects than were found in the ~nersi population sample: age was taken into "wi j., *1.4 + ) of tfao am at it bare repeatedly examined moat of ti dd bring. on anmAun faabits wan obt considaratiom Conan of Dmth.--A copy of the death certificate -?kdi*tu lor each of the 94 deaths. In addi tion, ra exanmreri hospital records, paatraartam witfa tto 336 ana ate Of the 32 men who were not told uo tfaeir imokinf habits by telephone and ladings (41 caaaol. as wnB as tire anpcd and pathologic reports whan surgery waa preformed (39 rases). We also reexammad hiatnlngic apachmam. the information by mail The local It was found that the death certificate was irmc- (who personally knew tfaaae men cunte in I I instances. However, thia did not alter I) aanartainari the smoking habits of 18 men. the picture as moch as ipigfat have been expected mernbew wipphad the information on three mam This accoonta for all of i 370 mam Table 2 shows their Hading hafaita max Jan 1. 1963, the man Dame rlaahhert since there were several compenrating entire. For example, in one instance the death certificate in dicated bronchogenic carcinoma as the cauae of death while a review of the hirtelogk specimen r ape an that data, even thwigfa aome showed that death waa due to plreaai meeobte. smoking Mite between 1963 and liana; but in another raatewcs eeartfy the raauao 158379 omm 48 mrm --ifciit ipMr, 39 suited in changing the reported cauat of death in i mm 01 043 0037* r M * r B ol i far lOLOOO mm uMagstPml ' Owing a dart, itmEt tnmchogenic CmreiL^Bnochofnic cat- m 1 > ? . 1t14f* m a a..s.tr 1 z u aM it m Mn ar 97 IStI tm 100 ia its ss ,I.S, .a.s. _... ts Iatw?e .. It 111M7 me M...i ... at.a.o. aMsl- acooanted for 24 while only about i wave exnected oa the j^FTi'iin TnTT *T* uSmSTi^ *********** * ^****** of gemni United Stetea naortaBty data for mates. However, as previously mentioned, at hand suggests that than wen pcopur- divided into many five-year age groups, eoene of tee subgmupe contained only a wnaQ number of men. In coneeqwaaoa, the long death rate was aomewhat more cigarette unbare among i of the very email sub- 970 subjects than among white mates in the Stetea as a whole, age being taken into . This might hove partially accounted isiMirlsi|iinir firipwM death rate at teabjects. For this and other raaaons wa made i of the expected number at bmnchopanw In three when tbe observed rate in a small wfgwqi aigwaml to be badly out of line, we arbitrarily made an adjustment to bring it mom into Got with adjacent figures in the table. Ureas adjusted figune which are indicated with symbols m Table 4 cany vaty little weight in the deaths, tbe smoking tsktti of tbs os; taken into couasdeutioa. Thfe was done as la are available on hmg canoar daaths in ra fatal ralndatton. AB of the rates wen then adJwtfld AdBowi Ltmg career death rates in the United Statae ham riaea etoadfiy yaer by year and were higher te the ""*^:~g habits of 44QJ00 men by American Cancer Si*xh wdunteeis in epidemiological study between Qc- 1960 and March i960 aed traced through in 1964 than tewing tea period 1960 to 1964 as a whole. Farthaanon. in tee study described above, we noted miffing aarioaaly iB people and. ea of the cut-off date far fii`g tee computer tape, 190,1964. Causes of death wenascertained from certificates, but afacmver mr*r waa men- ou a death certificate inquiry wee made of physician who signed the certificate. In case fiaiiM uient between the two sources of faaioT- - -thvaicuui's statement was accepted, ter . upoee at hand, we only made uae of date wnag the 52-month period hagiiming on June 1. we had not yet received death certificates for all of tbe men now known to have died during the sperifteri period of time. For these reasons, king cancer death rates in tbe study population were appreciably lower than those reported for white males in the United States in 1964. To compensate for this, we raised tbe rate of each individual smok:ng r-tegorv w* that the total hmg cancer death 9. end ending on Sept 30, 1964. The ""*-- of deoths occurring during the B? nraith I uae divided by tbe * at ana aBn at ' uiaregardmg smoking habits) in each five, year age group would be the same as that at all United Statae white males (based upon tto 1964 I at tbe period. This wae done by ftvw- life table sad the 1964 distribution at deaths by for aean in each of tea fallowing causes of death). The reouhe of theae coqnMhta (U never rawhed ngnlaily an shown ia Table 4. (It should be noted tfat Table 4 teams only such rates as wen required far I); <B) history of ngufar pipe oe dgn naofc- further nktetteal The rates aboma in Tsbfa 4 ware tern appifad to tee number at aabaatee marhan teams la each of the i rrmpnaihng internal crib of Tates 9. TTte Il966Mff fffafag SUaS piS *tSLaur* ` . \ ''F-V -'F Iqi 043 003SI tr ak" tabta a.-s tnf tetM- brW0Mq|H*brt** tor3704 to--u --w tor *mn< -- UMf > S ms* rwvw miaimi ^SS5*'. M9S8T' o am aaa um m in *>!!> mmm mm itwohii-- riliw mmlmaviH*t9eHmmn*UToMim* 4ms *M49rdar. ' fa this study, ww aabmtoa dust . iasoked cigarettes npfaifi Twenty-four of the warn \ cigarette smoking diadof whereas only 238 wen ex| ' K>- of &05 to l. From this it i Tabta 6.--Eapectag and Obw--d OaaSw Miow fC Art--. thratni dust greatly fac tnsWbrtwrsripossg tofcstMtB Oust 20ym or tangw cancer among cigarette wn f UMCt4 OtogtMd Teiaf cm+jmr. mlt vtmm Ohggndi CdEntcparcalat dtuff* tfICkM, 0town Obutsgd CrfL<acowrcot*aftatemgch cteM. toctum Ofagrthd c. EipacaMit oft> vmm uaternw* Otoggrwor* kibtefteit Cuictte Oh aMnrnm Ac anm* c-*ua-- Cipactttf Oh write# immr MMw tNMr 209% 426 m 64 24* Mi M 4U 0 46 144 2.1 U 44 77 77 4 I 6 11-2 7* 32 70S 21 * 14 2* tt 00 12 14 XT 162 3*6 au 14* 30 ii* Now we may ask bow greatly is i cfaogewir caicinoraa inciaaaed by t fecta of cigarette --l*g and ops dust To answer this shown in Table 4 foe never smoked regularly to the nnanber of ad with a history of regular cigarette smoking as i in Table 2. Thia indicated that only 0.26 at the| subjects with a history of regular cigarette amok would have been expected to die of bruncbogsnk| carcinoma if they had never smoked regularly had never been occupationally exposed to dust. Since 24 of than actually died ol that the ratio of observed to expected deaths ia 92 to fie. 24 divided by 0-26~92f. Thia appears to dicate that cigarette smoking plus occupatiaBal into consideration. The ranhi ere tmnmeriied in Table 5 winch shows the expected and ohaarnH number of lung cancer deaths in each of three exposure to asbestos dust incraaaes the risk bronchogenic carcinoma by a factor in the order < of 92 to 1. It dnuld be noted that i estimate doe* not take current amount of i smoking categories. smoking into consideration. Taking smoking hab-.U as Trtil 9- ? into can* (deration iTabie 5} s total of 3i bronchogenic rarrinoma deaths were expected whereas taking only age into consideration 2.3 deaths were ex pected from this cause (Table 3). Thua. perhaps ''tie of the excess bronchogenic carcinoma deaths Companion With Earlier Findings.- As t are started with a cohort of 632 asbestos imulat workers, the entire membership of the union to on Jan I. 1933. We have now traced each through Apnl 1967. Table 6 shows the i and expected numlier of deeths for ej*rh of ~vshi :*r attributed to the fact that there appear .. --n puifiontonnllv somewhat more ciga- periods (the first. 1943 to 1962. being previously reported ) .in.i fur the entire period. In respect .it- .visets among the 370 subjects than among respiratorv cancer (lung, trachea, an.! pleural of tiw same ages in the general population :r respect to cancer of the stomacn. colon. Tin- following -tatements are baed upon the i.nn. tne findings in the two penod- ,,rv in .sain -iKiwn in ladle .V Twenty-tour deaths from iurtonent. rrronehogeiur carcinoma occurred among the 370 subnet- impanel with only 3.16 expected, a ratio Comment if aUiut 7.6 to I. This is slightly higher than (mind The inert-a.--<1 nsk ol it<c;-..i-ia itnnnlv in <>ur earlier study which indicated a ratio of n.b genic can in-im:. .mil n. ~nthi n-ii' imnrig t.i 1 (not taking smoking habits into consider*- (ton workers " :kti.iI h. n- -booM tie evaluated t .on i It should be noted in this connection that the the knowledge *r- *t i. t..i\, f7(t stub tecta in this study had been exposed to light exposun- n~ i'nmarily i nJmtM dust Mimewhat longer than the subjects of pitiyed in con.-tun tmn work, ucuix nf tha mat hit previous stud', it he present 370 subjects arc they use I'niit.-rn iitfle . r on ashiwtos ssj survivor* as. ui Jan I. 1903. of subjects in the have only C\widitkuw of *w% piwtuoa study these nun nfiin work <>ot<kiura Of tt <f aubjerta whu never smoked regularly and operators in lactnry work. * ucnp thm* who wnoked only pipra or cigars, none died exposure Minin have f i*4 mnochogaur raixnnoma wharaaa (kid of these their, results haw genendiv r*3g*.fmgt |fat %jam ww rxpuctrd to die of Iwqgcsacec.Ttes suge v-pfU ttmi retrain to icS-t<tei!u#.dpw net' *; W:ht k* IVT ' aXT'"d ' *. W-UT'hr rite uf bfynchr.g^iid. Pi ' ltA --^ 043 0039 043 0040