Document kmLx9EVm62MY1JwveVdkg0nZO

7R2 Occttp Environ AW 2000^7:7H2-7?5 Mortality from all cancers of asbestos factory workers in east London 1933-BO G Berry, M. L Newhouse, J C Wagner ' Department of Public Health and Community Medicine, University of Sydney, New South Wales 2006, Australia G Berry Formerly TUC Centenary Institute of Occupational Health, London School of Hygiene and Tropical Medicine, London, UK M L Newhouse (died 15 February 2000) Formerly MRC Pneumoconiosis Unit, Fenarth, UK J C Wagner (died 25 May 2000) Cnrn jiKiitdcncc to: Dt G Berry gcr>(1blr?pub.l>e3lth.usyd.edu.au Accepicrf G July 2000 Abstract Objective--To give the observed and ex pected deaths due to cancer at all separate sites in asbestos workers in east London, and to analyse these for overall effect and exposure-response trend. Methods--The mortality experience of a cohort of over 5000 men and women followed up for over 30 years since Jirst exposure to asbestos has been extracted. Itesulls--There was a large excess of deaths due to cancer (537 observed, 222 expected). Most of these were due to can cer of the lung (232 observed, 77 expected) and pleural (52) and peritoneal (4$) mesothelioma. The exposure-response trend for all these three causes was highly significant. There was also an excess of cancer of the colon (27 observed, 15 expected) which was significantly related to exposure. There were significant ex cesses of cancer of the ovary, of the liver, and of the oesophagus but with no consist ent relation to exposure. Conclusions--The excess risk of cancer after exposure to asbestos was mainly due to cancer of the lung and mesothelioma. An exposure related excess of cancer of tlie colon was also detected but the possibility that some of these deaths may Table I Observed and expected deaths for all men and women Site (1CD-? code} All neoplasms (140-239) Buccal cavity and pharynx (140-148) ONoplugus (J50) Stomach (151) SinaN intestines (152) Colon (15J) Rectum (154) L'vcr,gall and bile ducts (155-156) Pancreas (J 57) Jjtryn* flfiJV Lung (162-163,231) Breast (170) liteius-cejvix (171) ' Uterus-otlier, and unspecified (172, 174} Ovary (175) Prostate (177) 'lirstiA (178) Kidney (I B0) Bladder (181) Melanoma (190) Sfcin-otljer (191) Utain and CNS (193,223, 237) Thyroid (194) Bone (196) Soft tissue (197) ITodghjn'te disease (201) Myeloma (203) l^ufcnemia (204) Other lymphoma (200,202) Mtsotlitliorna-plcural M csothc li o ma -pc * i tOncnl Other site* 537 5 J2 23 2 27 10 10 8 3 232 12 6 0 9 5 ] 2 10 0 0 a 0 0 0 2 3 7 4 52 46 3) Expected 221 58 3.24 5.78 23.U9 0.46 14.78 10.10 3.76 9.26 t.84 76.96 10.48 2.70 1.28 3.5 6 7.14 0.82 3.64 0.91 1.39 0.69 7.66 0.55 0,89 0.60 2.14 2.13 5.29 3.61 -- -- JO.flJ Obi.'Exp (95% Cl) 2.42 (2.22 to 2.64) 1.54 (0.50 to 3,60) 2,08 (1.07 to 3.63) 1.21 (O.Bl to 1.75) 4.33 (0 53 to !5.6> 1.83(1.20 to 2.66) 0.99 (0,47 tc 1.82) 2,66(1.28 to 4.89) 0.96(0.37 to L7Q) 1.63(0.34 to 4.76) 3.01 (2.64 to 3.43) 1.15(0.59 to 2.00) 2.22(0.81 W4.63) 0.00 (0.00 to 2.87) 2.53 (1.16 to 4.80) 0.70 (0.23 (o 1.63) 1.22(0,03 to 6.79) 0.55(0.07 to t.99) 1.45(0.69 to 2.66) 0.00 (0.00 to 2.65) 0.00 (0.00 io 5.35) 1.04 (0.45 to 2.06) 0.00 (0.00 to 6.65) 0.00(0.00 to 4.14) 0.00(0.00 to6.r0) 0.93 (0.11 to 3.37) 1.41 (0.29 to 4.12) 1.32 (0.53 to 2.72) Ml (0.30 lo 2.84) 61 (4G to 80)* 54 (40 to 72)* 'Rate pet 100 KKT peisop-ycars have been peritoneal mesotheliomas could not be excluded. There was no consistent evidence of exposure related excesses at any other site. (Occup Environ Med 2000;57:7S2-785) Keywords; asbestos; cancer; exposure-response The mortality of a group employed at an asbestos factory in the east end of London has been described in several publications.1"* The group consisted of about 3000 men and 700 women factory workers and of 1400 Jaggers (insulators).The factory workers were involved in the manufacture of asbestos textiles and products--such as prefabricated cement pipes. Crocidolite was used until the mid-1950s as well as amosite and chrysotile asbestos. The laggers worked on contracts outside the factory with intermittent and varying exposure, and some had worked as insulators before their employment by this factory. The men were those first employed between May 1933 and 1964 who worked at die factory for at least 30 days, and the women were those first employed between 1936 and 1942. Llie most recent analyses were of the follow up to June and December 1980 for women and men respec tively. Since that analysis follow up of the groups stopped. The previous publications reported exposure related excess deaths due to lung cancer and pleural and peritoneal mes othelioma. Several other cancer types were considered in some of the papers but the com plete listing of all cancer sires has not been published, hi view of the interest that occurs from time to time on the possibility that asbes tos exposure increases risk of cancer at several sites it was considered appropriate to give the results for all sites while summary data are still available. Methods Causes of death were coded according to the 7tli revision ofthe international classification of diseases (ICD-7). Tlte cause of death coded was that given on the death certificate except that where a confirmed mesothelioma was found, the mesothelioma was taken as the cause of deadi irrespective of what was on the death certificate. Cancer deaths have been taken as ICD-7 codes 140 to 239 inclusive. In previous reports codes 140 to 205 have been used. Tlie inclusion of codes 210 to 229 (benign neoplasms) and 230-239 (neoplasm of unspecified nature) involved only one extra death (ICD-7 237, neoplasm of brain or other part of nervous system). WrfrUM; Jt. J~^ <f~'I** * xUMjttm. ;w.j .1 t .1 n is iC 0 "S d d s. IS le y d ir re i .d i ;r i u id >e is i iO s- i re l:LI i i'S j S ! al le I ill i i ie of :d ol as le le :n In al !9 . of tt er The mortality was assessed by comparing the number of observed deaths with the number expected based on sex, age, and period specific death rates for England and Wales, cal culated will) rhe person-years method, and the tables of person-years produced for the most recent previous analysis.8 The first 10 years after first employment in the factory were excluded. In previous analyses the mortality covered the period from 1943 for men and from 1946 for women (10 years after first entry into the study) but because ofthe availability of cancer death rates for all the sites attention is now restricted to mortality from 1951 on wards. The effect of this change is trivial as the period excluded contained only 12 (expected 11.7) of the 1249 deaths from all causes and two (expected 2.0) of the 539 due to cancer. Exposure was classified by degree (low to moderate versus severe) and duration (2 years or less and more than 2 years). Fuller details of the classification or jobs were given by Newhouse.1 Briefly, the low to moderate category included administrative workers, store workers, those involved io die manufacture of insulating material with less than 20% asbestos, and maintenance staff. Workers in this category did not work regularly in areas where the 1931 asbestos regulations applied. The severe inten sity category included workers involved in sectional pipe malting, the manufacture ofinsu lating material with a high asbestos content, workers in the textile and mattress sections, openers, disintegrators, and those employed in the disposal of dust. These jobs were all covered by the 1931 Asbestos Regulations. The terms Tabic 2 Observed and expected mortality for separate exposure groups At1 neoplasms Buccal cavity and pharynx Oesophagus Stomach Small imearinea Colon Rectum liver* gull bladder and bile ducts ikancmas Larymr Lung Bi^i Uterus-cervix Uterus-odieri and unspecified Ovary Prostate Testis Kidney Bladder Melanoma Skin-oLher Urain-CNS 'lliynud Butie . Soft Lissue Other lymphoma Myeloma Hodgkin's disease leukaemia Qbsersied texpected deaths Vfbmcn Severt Lffiuhnod <2y Scveve >2 y 12 *7.27 0 0.09 } 0.16 J 0.67 J 0.02 0 0.72 0 0.34 0 0.15 1 0.29 0 0.02 2 0.77 l r.57 1 0.39 0 0.22 2 0.54 60 26.02 0 0.30 2 0.51 1 1.96 0 0.05 2 2.29 4 1.08 2 0.47 l 0.95 0 0.08 14 2.97 5 6,09 3 1.61 0 0.74 2 2.12 57 11.18 0 0.13 2 0.22 3 0.88 0 0.02 1 LOO 0 0.47 0 0,21 l 0.41 0 0.04 21 1.22 6 2.59 2 0.70 0 0.32 5 0.90 0 0.0B 0 0.13 0 0,04 0 0.02 0 0 19 0 0,04 0 0.03 0 0.02 0 0.30 0 0.07 0 0.04 0 0.16 0 o.zs 1 0.39 0 0.18 0 0.07 3 0.78 0 0.12 0 0.09 D 0.07 1 0.35 0 0.25 0 0.16 l 0.57 0 0.12 0 0.17 0 0.08 0 0.03 0 0.33 0 0.05 0 0.04 0 0.03 1 O.lp 0 O.JI 0 f>.Q7 1 0.25 Men bnufiwod Lonftnod Severe <2y >2y <2y S&xri >Zy 49 40.03 l 0.63 2 Ml 4 4.48 0 0.08 3 2.48 2 LS9 1 0.66 2 171 0 0.39 24 16.06 0 0.05 57 32.1 L I 0.49 2 0.68 3 3.67 0 0.06 3 2.01 0 1.55 3 0.52 0 1.37 0 0 31 23 12.94 0 0.04 102 45.86 2 0.66 2 1.26 9 4.97 0 0.IO 3 2.70 3 2.05 2 0.76 2 1.98 2 0-43 43 19.09 0 0.06 128 32.56 1 0.50 1 0.87 5 3.85 0 0.07 6 1.97 0 1.53 2 0.54 l 1.38 1 0.33 67 13.56 0 0.04 1 1.73 0 0.18 0 0.70 2 1.43 0 0.24 D 0.13 0 Lil 0 0.08 0 0 17 0 on 0 0.67 0 0,38 0 0.42 2 098 1 1.67 1 0.11 J 0,53 1 1.24 0 0.16 0 0.11 2 0.93 0 0.06 0 0.12 0 0.08 1 0.48 0 0.30 0 0.27 2 0.73 0 1.57 a 0.20 0 0.84 K 1.54 0 0.28 0 0,14 2 1.77 0 0.09 0 0.19 0 0.13 0 0.80 1 0.45 0 0.51 0 1.12 t 1.43 0 0.09 1 0.51 3 L.20 0 0.15 0 0 10 1 0.96 0 0.06 0 0.L3 0 0.08 0 0.48 2 0.29 1 0.28 0 0.7! l.ttigcri 72 26.54 0 0.42 0 0.77 2 2.61 1 0.06 7 1.62 1 1.18 0 0.45 0 1.17 0 0.21 38 10.35 0 0.03 2 0.74 0 0.23 a 0.54 2 0.80 0 0.26 0 0.08 0 1.27 0 0.06 0 0.12 0 0 10 1 0.58 Q 0.28 1 0.39 I 0.77 . fmow. occcrmncd. cam 7SI h jl L 1 Beny, Nfwhcntte, U^jnn' Table 3 Observed numbers of mesotheliomas, rales per 100 000 penon-yeais and adjusted rales for 25 years foBota upfar separate exposure groups Wb/wrt Lamhnod Severe <2y Mesotheliomas (n); Pteunl Pcxiioneftl Total Fmon-yctirs Rate Adjusted person-years Adjusted Tate 0 1 2277 14 2942 34 9 7 16 10222 156 15048 106 Snwrr >2y 4 4 a 4647 172 601ft 133 Mill Loto/nuki <2y i 4 1 5 15193 33 13043 38 Lotrhnod >2y 6 4 10 9333 107 7537 133 <2y 9 11 20 17966 111 19221 104 Setter* >2y n 13 25 BBSS 282 8120 308 Laggers 7 6 13 16795 77 7075 164 low to moderate and severe are relative to the period during which the factory operated, and the exposures in the low to moderate jobs were usually higher than those specified in the 1969 Asbestos Regulations.' Aniosite, chrysotile, and crocidolite were all used and much of die exposure was to mixed types. It was not possi ble to isolate groups exposed to a single fibre type.* The laggers (all men) were kept as a separate group. Most of the workers in all groups had been followed up for over 20 years, 41% of the male and 80% of the female production workers had been followed up for more than 30 years, whereas 9% of the laggers had been followed up beyond 30 years.' The ratio of observed to expected deaths was used as a measure of excess mortality, and sig nificance was calculated by taking the observed number as a Poisson variable. Hie exact confi dence interval of die ratio was derived widi the relation between the Poisson and the x1 distri butions. For assessment of an exposureresponse relation the exposure groups were ranked in increasing order of exposure as low to moderate (all durations), severe (2 years or less), laggers, severe (greater than 2 years) based on die excess mortality due to lung can cer. 'Hie exposure-response relation was as sessed by a trend %* test.10 For many of the sites the expected number ofcases was small and the exposure-response assessed with an exact test computed with StatXact." Two tailed signifi cance levels are given and for exact tests these are double the one tail probability. For mesotheliomas, as the expected number was very low, the incidence was expressed as an absolute rate. Trend with exposure has been assessed by tailing the expected numbers of mesotheliomas in the four exposure groups as proportional to person-years weighted by time since first exposure Taised to a power of 3.5, and the rates have been adjusted to 25 years since first exposure. Results Table 1 shows die comparison of observed and expected mortality over the whole group of men and women. Those classified as other sites are peritoneum (ICD-7 158) not confirmed as mesothelioma (four); endocrine (ICD-7 195, two); thoracic secondary (ICD-7 165, one); and other unspecified (ICD-7 199,26), As well as pleural and peritoneal mesotheliomas there were five sites with a significant excess of deaths: lung (relative risk (RR) 3.0, 95% confi dence interval (95% Cl) 2.6 to 3.4), liver (RR Exposure group Figure t Exposure-response rdartorsforpleuia! and pssduoneol mesotheliomas. Mesothelioma rates are per 100 000 person-years adjusted to 25 years afterfust exposure, llte 95% cotrfideaa intervals are shaam. 2.7,95% Cl 1.3 to 4.9), ovary (RR 2.5,95% Cl 1.2 to 4.8), oesophagus (RR 2.1,95% Cl 1.1 to 3.6) and colon (RR 1.8, 95% Cl 1.2 to 2.7). In table 2 the observed and expected mortality are shown for the different groups of subjects. In table 3 the observed numbers of mesothelio mas and the rates and adjusted races are given. For the seven sites with a significant overall excess there were four that had a significant trend with exposure: lung (p<0.001), perito neal mesothelioma (p<0.001), pleural mes othelioma (p=0.011), and colon (p=0.017). For cancer of the ovary the significance level for the exposure trend was 0,18, but there was a significant excess in women with severe expo sure of more than 2 years. For cancer of the liver the excess was distributed across all the exposure groups and' the exposure trend was not significant (p-0.77). This was also the case for cancer of the oesophagus (p=0.98). 'Die only other site for which the exposure-trend relation was significant at even the 10% level was the breast (p-0.08); there was a non significant excess in women with severe expo sure of more than 2 years but little overall excess at diis site. The trend relations are shown in figures I and 2 for the four sites which are in excess overall and have a significant relation with exposure. The increasing risk of mesothelioma with increasing exposure is clear (fig 1), but stronger for the peritoneum than for the pleura. There was also a steady trend in relative risk of luug cancer with increasing exposure (fig 2). The excess in cancer of the colon occurred only in the laggers and in men with severe exposure for more than 2 years (table 2). fvuHi tS ijwin M Jui-Vsty ,,x,ien at ms* l **s*JS*<H t VtJ -Hit nsh material.1 ' Ofthe 52 pleural mesotheliomas 37 had been coded as ICD-7 163, 11 as lung can cer (ICD-7 162), and four as other sites. Of 46 peritoneal mesotheliomas 26 had been coded as ICD-7 158, nine as other unspecified (carci nomatosis) ICD-7 199, six as cancer of the gastrointestinal tract (two stomach ICD-7 151, three rectum ICD-7 154, one pancreas ICD-7 157), one as cancer of die ovary (ICD-7 175), and four as other causes. It was not possible to check all cancer deaths as pathological material was not always accessible and it is not known moderate c 2y Exposure group > 2y for how many of the 27 deaths from cancer of tire colon the pathological material was checked. Although none of the peritoneal mes Figiive 2 Exposure-response relations fur cancer ofthe lung and cancer ofthe colon Rates are relaritv risks compared wish national rates adjustedfor sex, age, and period. The 9S% confidence intervals arc shown. Discussion The overall excess was assessed on all men and women. There was evidence of excess lung cancer in the low,..,i exposure group (Low to moderate 49 observed to 29.8 expected) and 6 mesotheliomas occurred in this group. Therefore, the exposure was sufficient in all exposure groups to produce an effect related to asbestos. The excess deaths due to cancer of the lung and both pleural and peritoneal mes othelioma and the exposure-response relations for these three causes are well established. The only odter site which had a significant excess and a significant exposure-response relation was the colon (ICD-7 153; RR 1.8,95% CJ 1.2 to 2.7, p=0.017). In our previous report results for the wider grouping of gastrointestinal cancer (ICD-7 150-158) were given and an overall excess noted but without a significant relation with exposure.1 For this combined otheliomas identified had been certified as cancer of the colon, three had been certified as cancer of the rectum, an adjacent site, so it cannot be excluded that a few of the deaths certified as due to cancer of the colon may have been peritoneal mesotheliomas. Therefore, it cannot be accepted that there is an excess of cancer of the colon attributable to asbestos unless there is support from other studies of asbestos workers. Many of the sites have low observed and expected mortality. Cancer at these sites cannot contribute much to the total effect of exposure in terms of the absolute number of excess deaths compared with the large excesses from cancer of die lung and mesothelioma. For rare causes an excess of relative risk would be difficult to establish from a single study and a meta-analysis is required. Such a meta-analysis has recently been carried out for cancer of the kidney.'* The results given in this paper provide die information necessary for any future meta analysis scudy of asbestos workers. grouping there was a significant excess (ob served 101, expected 67.2, RR 1.5,95% Cf 1.2 to 1.8) but the exposure-response was non significant (p=0.10). For colorectal cancer Wc are grateful to Professor Julian Pcto {Institute of Cancer Research) who provided the death rares for the cancer sites fox England and Wales from 1951 in electronic form. (ICD-7 152-154) there was a significant excess (observed 39, expected 25.3, RR 1.5, 95% Cl 1 Newhousc MI- A study of the mortality of workers in an asbestos factory. BrJ IndMed l96Q;2fi;294~301. 1.1 to 2.1) but again a non-significant exposure-response (p=0.10). The significant 2 Ncwhoiuc MI* Wagner JC. Validation of death certificates ill asbestos workers. BtJ ind Med 1969;26:302-7. 3 Newhousc ML* Berry G Wagner JC, tt al, A study of the and exposure related excess of cancer of the colon was diluted in the wider groups by cancer mortality of female asbestos workers. fir J Ind Afed 1972129:134-41. 4 Derry <j* Newhousc MI* TVitok M. Combined cflect of of the stomach, rectum, and pancreas, which , showed little excess and cancer of the oesoph asbestos exposure and smoking on mortality from lung cancer in factory woifcert. Lancet ]972jii:476-9. 5 Ncwliotise ML, Berry G. Atbescoa and laryngeal carcinoma agus and liver, which showed excesses not {letter]. Lancet I973;ii;615, strongly related to exposure. The excess of 6 Neivhoure ML, Berry G. Predictions of morUlity from mcsothclia! tumours in asburtos iiutary workers. Hi J Ind cancer of the colon was confined to men who Mat 1976)33:147--51. had worked as laggers or been severely exposed 7 Newhousc Ml* Berry G. Patterns of mortality in asbestos factory workers in London. Ann i^Y Acad Set I979;330: for more than 2 years. 53-60. As with all mortality studies the results depend on the accuracy of cause of death 8 Newhousc Ml-* Berry G, Wagner JC. Mortality of factory workers in east London 1933-80. UrJ Ind Med 1985;42:4- IL. information. To be able to compare the observed number of deaths with the expected 9 Berry G, Newhouse ML, Antonis P. Combined effect of asbestos and smoking on mortality from lung cancer and mesothelioma in factory workers, fir 7 Ind Med 1985;42: calculated from national records the cause of 12 18. 10 Armirage P> Berry G. Statistical methods t'n medical reuarth, death as recorded on the death certificate was 3rd ed. Oxford; Blackwell, 1994:410. accepted except tfiat some deaths were reclas sified as due to mesothelioma, and some origi 11 Cytct Software Corporation. StatXatt: statistical softuore for txatf TTOU-pitrametric tr\fert\tcc, user manual version 2. Cambridge, MA: CYTEl Software Corporaiiou* 1991. nally classified as mesothelioma were not con firmed as such, on review of pathological 12 Sali D, Boffetta P. Kidney cancer and occupational exposure to Hsbestos: a meta-analysis of occupational cohort studies. Conor Cauics Control 2Q00\11:37-47. zuwzv. occenvmtid. com