Document gbVyeeVvkwkkOdM40ykon85r9

r C 1 1 PLAINTIFF'S i EXHIBIT f UO^SiD J An Ipiderioiogical Study of Lung Cancer in Aabeatn* Miners Zsiniel C. Eraun, M.D., and 7. Ivld Truaa, AKA .Archive*, Juno 1956, Yol. 17, 3o. 6 Reriev by Tirana F. Nancuso, M.D. Chief, Division of Indus trial Hygiene ' Jfovccber lb, I960 /f rl rut:7e Revievs: .^e-ati~rs: ^ 'C TV mRCSlTTgl MATERIAL 1. Early literature refers to cancer cases vhiea occurred simultaneously vith csbestcals. In other uords, reprieved thca cases of esbestoais to find vhat percent of cancer (lisg) occurred in this Group. 2. Essslc: Herrvetber (195^*) l6.0 ' Gloyne (1951) 1^1$ 1, Sneoe.- (1952) states 1-YT% of cases of ashestcaia, after 1} to 20 yean latest period, develop lung cancer. 2. Itordacrtnn and Sorre - nnlnal experiments- produced lung cancer in nice vhich wore exposed to eabestca dust. 1. Sauce (1939), found no cases of lung cancer among c2D cases cf asbestos is be examined. 2. Hoi,lab (1S-U2), found the number of cases of asbestosis vith -"`I us ) f-tneuso: tr 3. Venclius (19^7), in 1^6 x-rayed cases of osbestssis among ^76, found no lung cancer associated in the group. Lung cancer occurs in asbestos uoriiars vith and vithout asbeatoais. All studies vers related to cases of lung cancer associated vith asbeatoais and vben this simultaneous requirement occurs, it is usually a untiller percentage. The Wegelius study nsJtes the ossunptloa Doll: .-'ancuso: 2raun: ftaneuso: that for lung cancer to occur, tills would be only when . es'oestoais 13 present by x-ray evidence. This say or nay cot be true. t_v-; cancer can occur in these wariers as a cause of death, \rlthout asbeetoaia as a secondary cause. 3y considering only the sinultaneous occurrence of lung cancer and asbestosis, the'investigator ia automatically excluding a large potential of c*eatra vttn .to diagnosis cf uabestasis, even though exposure end duration of exposure have been, established. Doll (i?55) studied records of men vbo warned for at least 20 years in exposed situations; found that in workers after 20 years of exposure, the risk i3 10 tinea as great aa general population (Found ol cases of lung cancer-studied 'H ? men. vho bad warred for 20 years cr tore.) In Doll's study, he excluded these vho died frog, other causes, after shorter employment. It is evident that lung cancer eases could have occurred arsons employees vith less tbaa 20 years esplnyoe^ exposure, depending, of course, on vbat is found to be the number of years exposure required and the latent period. Cites selective factor of Dr. Gloyne's series of l4.1J of ' autopsy coses saying these cans oa part of unusual group of lung eases to autopsy. Also cites percent of lung cancer at London Cheat Hospital was 21.37?* This could very veil relate to all the lung cancer-eases vhich coce to the hospital, like ccuing to Dr. 0chaner`s Clinic, so this port of the criticise is valid. However, association . of asbestos ia with lung cancer i3 not a bias that exLsta by virtue of the Clinic-so observation of Gloyne ia still an unusual su'd valid suggestive lead. 3 Lung Career la Asbestos Minors l' Dmun: Refers to Klota vbo found only b casea of lung cancer la 173 coses of asbestos!**. Initial observation la recard to the limitations of this interpretstlan still bolds. Other cases could fcava occurred but not simultaneously. The alrailtaneous requlreseat places a restrictive bias la actual situation. f-PPTlCWT! by Eraun :Jouree c: Data L. 2roua used all persons vbo had been process ad through tbs company clir-ic at Thetford Mines since 15^7 Is Quebec. 2. Established cohort, vith total exposure of 5 O" rare years, vbo vers oa employEect rolls In 155^. Tbs office force end non-exposed vere not included. - Ffcncuso: I question vbether Ersun is alloying suffioieat suaoer of years for latent period required for lung cancer. If tbs eutaff date is 1955, then the cohort latest period is only being tested against a period of 11 years, 25^5-1955; question whether there is enough cf this population in the cohort with exposure of 19 yeses or core. For exaeple, if they (the mafrer of vorhers vith ip or more years exposure} represented only of tbs cohort, the * >0 expectancy of lung cancer would definitely be diluted b7 the other The cohort folloved through 1955vfcetber alive or dead, ". > be statea-all but a smll number cf thtsc vers accounted for as either living or dead." This vaa 133 out of 5,091- If tha 133 Vera found and only 1 lung cancer recorded bad occurred, the entire conclusion of the Btudy would have been different. Certainly a vary slight thread to drav such definite conclusions. - U. r Cancer La Asbestos Sinere Emun: 1. Through Office of Vital Statistics tabulated lung cancer rates by o for years 1950-1955, Inclusive. * 2. Group policy coverage of one eocpsoy studied for ar cancers of lung ood Braun states: "Very fev cot coveied by this policy- cod those who leave industry cad are cot covered, ere a erall cudber rfancuso: Eov rany? This nay affect results. Draua states "fev cases la vtiich lung cancer is strongly suspected but not proved as the cause cf death wtb considered separately, " Knocuso t Dentes from ling cancer vere detemined frea clinical, rscords in the radical service of industry and checked by rrarn of death certificates and the Insurance cocaany records. However, he refers to only the croup insurance plan corerag* of industry. Cohort-5,95<5, placed in three (3) categories according to increasing decrees of exposure based on veighted average of years, etc. yjzi ceo: Cable l--66i of cohort in 20-kk rrtnrs. s' . { Population veighted to tha young age group'vill not shew natal incidence of lung cancer found In the older age groups, therefore, '*' rates of this group as a total for cancer vill be lov and biased, a dilution, factor cf considerable proportion. Severer, the age specific rates for 20-^fc, if higher than the control, would bo significant. Again, however, one rust determine. hov may in this group worhed for 20 or sore '/ears since this is probably the Istact period, otherwise the rate becoaos xaarhedly diluted. The acber cf this group by the very nature of the ages, 2D-J&, would indicate that i\ \ the merler of wortare of 20 or core years would be very stall, . ; too amil to use" statistically since the cohort vas only followed`for I. . ' 11 years, how cany vere there vith 11 or core years exposure in the / age group of 20-U4 comprising 66 af the total cohort? 5. Cancer la Aaboatoa Miaara !*auruao: rfcncuso: Msncuso: ttocusoi Table 2. The .-.iar.ber and percent distribution by length of - er^loywnt 3boved only 30 with 20 year* or acre exposure{ 70^ ta&~ leas than 23 years. If It takes 33 or sore years to develop 1-^3 nance: then the dilution factor is 7&p! the bag cancer rates should be based on the ;p>* Bren should vo oooaider that 10 or sore years am required, then them is still TPp of the cohort vhich would not be i-vQ-rrt in the population when the rate* are eAi-rrO-v^wd. licterially, would Increase the rates. Itotiea, however, la addition that the length cf emlo^cgrt .. is cot rivefn,,:ibv ar-e srcus. " Could be as Mgh as 50*i In the age .prcu? vith less than 10 years of crployrent. Doa't hoov actual percent but represents a high H-firrfc.-trv factor. Table 3. rxrrjnure categories. Again,in categories cot related to the age groups like 23-i-l. T"-'" 1 r- 1, Habi*'-'*. ** Sot misted to age groups* Definition cf 3nokers-5 cigarettes ^ TM ^ "*-*-* * It- pack a day, etc. Table 5. rfunber cf Cases. 1V -v ^ Defined proved cases of lung cancer as "diagnosis snggssted by - autopsy, surgical section. Microscopic examination. " "Suspected csses-3, diagnosis in doubt but evidence points to cancer." * Basic error here, la f^yei^g this type of "proved" case criteria of autopsy or surgical section, vhich does cot apply to ' the control of the general population, the rates for ling cancer la the control are derived front lung cancer as listed co the death certificates. There is co indication that the sacs criteria was applied to the general control populsticn. Actually, **>< vould be irgjoeflibls without reviewing all ths lung eaoerr case* of the county cr ra-establlshlng theIr entire clinical record. Seccaily, the general, population nay not have Moan opportunity of r^r*-1^! care. **<. could ward both ways, mcc Juries other eaae* without such confircatloa. Controls include both eoixfimed ard ixamnfircsed, usually ccncocfir==d jrcup is larger because of cedi cal or available care. la discussion states "If ha uses the 3 suspected cases. Table 12 would be statistically aimpair!cant- " Be rpes on to acolyte the 3 questionable cases because this rakes the study so close to the significant level. :soi Table d. lung Cancer Deaths by Ana Crouos. There was ooJjr 1 case of the 9 proved cases ia-the 23-41 age ^cup. Beca.il that this age group bed oca of the pcoulntlor. cf the cohere. The rata for 23-44, per 100,000 core years cf saqpomrre, vu only 4; acd rate for 45-54 vas 15. (Comprised 17$ of cohort). -' Kates ere based on very mail sunbers, oca each ia 23-44 and ~ 45-54. Cannot xae total average rate cf 25 because of carted dilution factor of aga 20-44 seta of 4 which ccegirised 60$ of popalatlcu; t ' cost take age specific ccamariscsa with the control- Table 9. r'~~ eraser Peath3 by Length cf Ihrlovsest. , Shows that caly 1 proved case was faad in the leas than 20 year length cf erploysent and this group cvsrrisart 70$ of the cohort. rates under 2D yearn length of ctployaeat were 7 por 100,000. This again dilutes total rate and Lowers average rate to 25* Bote that the rates were high ia 20-29 yr. length of rryloyrrat Group which was 54, and the 33-29 yr. length of eeployrmt was 15/100,000 can eroloyrant years. * Brava; Discussion cf 2Uo aca over 4o yearn of age, followed for 6 years, did cot develop lung cancer* / Tnbls 13. Lmx Cancer Deaths by Sposure Catscory states rates do not lacraa.se by catagory of exposure. alia is proof that asbestos Is not a carcinogenic agent." "Thus V. Categsries, however, are not related to age distribution of the population^ for example, 65^ of population in tha 20-11 ago group. Do not xnov hov such a contribution Is rade to these various categories, I, II end IU. Hiis =sy ba the reason vhy tha rates did not rise with category Increase fron I to III. Secondly, workers are so sra.ll, 2 cases in category IU; the audition, of 1 or 2 cases raxes sireabla difference. Table 11. Categories I, II and. HI were comprised of 1,795 persons with employment only of 5-9 years and comprised 3&P of cohort population ELdd:.-.g tha ID-19 yrt. length of employment group gives 73^ of tha population. However, of these groups at least 66 must have been in age group 20-11; 1300 out of 1772 vere in category m-froa employment group leas than 20 years; lU00 out of 2,150 vere In category II; 1300 out of 2,COO In Category I. It is obvious that these categories are biased by contributions of different age groups end higher numbers under 20 years in these categories. i Therefore, one cannot use this approach because the categories are weighted by a larger number in the younger age group; even in category HI which would be less lihely to have cases of lung esnee occurring. Braun states "Average number of years of employment in each exposure category is almost identical." Ee does cot take into consideration distribution by age group. nccr in .-sbestoe riicers Tub 13 12. _ States not a single cslm cf ling cancer oocurrcd in 1,265 w" cna-anokera of both "proved" and "suspected" cases. Tables 13,1k,15. _ , _ 7ears . States -'Itb looker exposure average (2.3 f these sack era) and greater age (data does act dbcnr this) coe would expect the roo-snekiag group to sfccv a higher rate If l;sig cancer was due to asbestos." Actually ha docs cot shcr ia what ages these cases occur la the "saokers." ' Table l6, Cocoa-rlsor. cf Cobort Ebpsriencs vlth Province of Cuebeg. Gives - Annual rate-per 100,000 Province 22.5 Cohort ~" (Zhricdiag Asbestos workers) Thtai 33*3 Proved 25*3 Be gives =0 reason vhy tha suspected cases should sort be . included. This would be statistically slgoifloact sloes sobs exclusion factors are cot applied to tbs coatools. Secondly, be feels that the geaersd population Is cot studied os diligently as the dinars aad, tie refora, ths rats Day be low In the control, laylying that the difference, therefore, is ant real. . fact that the cohort did not necessarily show a progressive increase ia these years is cot a valid argneat became variations occur depending upon tha latent period: aad, recalling the 6o ia ^conger ago groups, coe nay find that ia ths next ID years . there would be a rise ia lung cancer after tha latent period is fulfilled- ' 9 Cancer la Asbestos Xlners . Hanguibt m~: Tabla 17 *' Brain use* a claaslficatlca of "prinary'' and "proven" a* determining whether death certificate carried the Laclualon of autopsy or surgery, etc. Thia la not a valid cacporiaoa. Thera La act iia a era degree of accuracy ia recordlag data oa death certificate*. Cable 13. ' Gives cccperisocv cf actual and expected mrvrxr af lung earner death* 07 age aaong asbeotoe aloere. 'Snrjwt first, Braun uses tie sod 1955 province rates rather thsa the year* of actual study frsa which the population was stalled-. bed a higher rate, and with th* control higher, it beecaes lose lively to plch 19 the difference is the cohort because cf the saall embers involved. 3h the 6p year* aad ever grothJ, there vers 5 obierred deaths compared to the ejected cf 2. 3e, however, points out sad ~ crpirslace that this includes 1 cf the "suspected" eases to isdic&te what appears to be a suggestion cf statistical evidence. Be adds ` that "it 1s rather lihely that ths rate for the general population is understated la this age group for the obvious reason that ths exact cause of death In ths very old ia not o natter cf the asm intensity of interest as it Is In the younger person." Tils Is sot true. 3a expects to irply that the rata for this group would be higher In ths control and, therefore, the differences observed by the cohort in this age group would not rwin anything. Bmuai Si Tibia 18, say* neabera of cohort have not died frea cancer at an age earlier than general population. hbmisoi What be has left cut is that the cohort consists of 6&i of age Croupe of 20--U*, cad k,CG0 out cf 5T30 have leas tbw 33 years ^ -- Lung Cancer 1 Aabestco Miners I'n.uruao: Braun: Maneuso: cxparieneef so, if the 2D-Wj group did rot have a oufficiant latent-' period, they v*xdd :ot hare lung cancers. Recall too ti*.t the v* cohort van followed only Tor 6 yaars. ^ to tha coanoat about tha ZhO with oora than lO years of enplnyaent, this aay be c selective factor with the tardy currlvors. Thera in some question whether be really got all the ainers who retired, ttooa vho left tba area, etc. ` Siscnsa Ian-cage &i7, Ert.cn aaJcea tin case again oa tba total nt-ns-oll ages, 20.3 per 100,000 for Canada. Cocports to 25*3 Ptr 100,000 proven cases. 2* 33-3 for total cases included tba suspected. feel that Table li, sga suspected, tend a to srove ratber than dioorove, particularly' vbcn rccogn I tiri3 that 6e of tb cohort in 20-^v use group were i_i tba 72? under 20 years exposure. large populatiea cf cohort vritbout sufficient follow-up baa autocstlrally diluted tba' results. Actually by a-ca specific rates, the aontrals are lower than ~ the cohort study as it no? stands. If cohort van fOUowd longer thin t *' would show np core strikingly that limitation cf tire period of follow-up influence* absence of cases. to sot agree with stateaerct ha cakes that "tbs re are ao isportant. differences between tha rates for asbestos ri.nrra acd general populstloa of Qae'oec and Chcoda. " Ossa proceeds to cccyare vltb Edited States sates vbleb axe higher. This is sot valid because of mrkad Industrlallsstion is our country cceyarod to Cnnaia. Pat! o>3 of dincuaalra. Uovl Speculates that about ^OtOCO persons enqxeed througho'rt the \Krrld have 1,000,000 ran years of exposure. Since only lyO canes reported in the literature, cItcs rata 15 per 100,000. 1 1 liiT-a !*- tr-- in /nbcatO* .wln*rS Iti vraa: (coot 1 r.'Wri ) ,- Ttt!% is ridiculous because rainy case* of I'.r'.g cancer never are rcporsad in the literature alrply because studies were cot ends La the aabcstca plant*. Tbturyla; Halted States reports in literature are not an accurate gauge as to ufaet has or bos not occurred as fax as lung cancer la concerted. fbnr.3a: Table 22. This table shows that lung oaacar rate of tbs county It vfeieh tbs asbestos plants vers located bus rate 2 tires tbs adjacent ooirrclas, f" ' 13.9 to 9*^* Ibis la a valid corps.riser., certainly cakes a better control. He baa be using the Province of ^uebs as a cactrai vuich I believe includes icr.traa.1 which raises the owra.ll rate cf tbs control. Srauu; Refers to additional casts net tnclrricrt in tbo cohort, for^pxssale, the 9 prior to ths beginning of study due to lung cancer. /\ i-l* Jbnnuso: --------------- 2raun refers ngsln to "at least 7 cf 23 proved lur>g esneera were I sot accompanied by asbeauaals." This is cot the point about dealing ' i* i only Tith ths histologically proven esses. 15s should have used os a i : control, the age specific rates of the surrounding counties iusteud __ l' * ^ of the total Province which usa weighted with other industrial areas, [which raised the total rate of the central. If ha had ccepared with the adjoining counties on an age specific basis, it would bars been statistically eigvlficont beesuee the ooe county was already 2 tinea the rata of the adjoining oocniy. Els cose is too weak. Hrtira eradiation binges on the additloa of 1 case. Ills ooccluslons aboull have been either that he bad not I dieproved adequately that lung cancer la cot associated with asbestos!* \ or that a valid enaver could only bs deterained vtaer. ths oobort is . fnllovod for a longer period cf tioa, equal to ths latest;period. ooo