Document 0gr7DE991N3Er86RnBge9ezBR

FILE NAME: Z< DATE: DOC#: Z< DOCUMENT DESCRIPTION :ZKZZ ZDZZZWZZ British Journal of Cancer (2009) 100, I' 75 - 1183 2009 Cancer Research UK ,A.I! ng~ts reserved 0007 0920(09 $3200 www.bjcancer.com Occupational, domestic and environmental mesothelioma risks In the British population: a case-control study C Rake', C Gilham', J Hatch', A Darnton2, JHodgson2 and JPeto"''l 7~'DH/nTesp,tloUwrtKtemoenftCoafnEcepridRemesieoolrocghy, aSnudttoPno,pSuulartrieoyn 5HMe2alt5hN, GLo,nUdoKn LScEhpoidolemofloHloyggyieUnet1Iat,nHdeTarlathplcaonl dMSedaifCeitnye,ExLeocnudtIoVne.UBniovoertlseity.MKerespepyeslidSetreLe2t.0 L3oQndZo.nUWKC lE We obtained hfetlme occupational and residential histories by telephone interview with 622 mesothelioma patients (5 12 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime lisk (LR) estimates for Britons bom In the 19405. Male ORs (95% confidence Interval (Cl) relative to IOW-risk occupations for> 10 years of exposure before the age of 30 years were 50.0 (25.8-96.8) other construction workers, for carpenters (LR 15.3 (9.0-26.2) for I in 17), 17.1 (10.3 - 28.3) for plumbers, electncians other recognised high-risk occupations and and painters, 7.0 (3.2- 15.2) for asbestos may be encountered. The LR was Similar in apparently unexposed men and 5.2 (3.1 -8.5) In other Industries where women (~J In 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% Cl 1.3-3.2). No other environmental In all, J4% of male and 62% of female cases were not attributable to occupational or domestiC hazards were identified. of the male cases were construction workers, and only four had worked for more than 5 asbestos exposure. ApproXimately half years In asbestos product manufacture. Bnttshjouma/ of Cancer (2009) 100, 1175-1183. doi:10.1038/sj.bjc.6604879 www.bjcancer.com Published online 3 March 2009 2009 Cancer Research UK Keywords: mesothelioma; case-control: amosite The British mesothelioma death rate is now the highest III the world, with 1749 deaths in men (1 in 40 of all male cancer deaths below 80 years of age) and 288 in women in 2005. The projected lifetime risk (LR) of fatal mesothelioma in all British men born in the 1940s is 0.590/0 (Hodgson et ai, 2005), or about 1 in 170 of all deaths. Substantial exposure to asbestos dust continued until about 1970 in parts of the asbestos industry, and until the early 1980s in the much larger workforce in construction and other occupations in which asbestos lagging was applied or asbestos insulation board (AIB) was sawn. The death rate is still increasing above 60 years of age, but the reduction in asbestos use since the mid-1970s has been followed 20 years later by a rapid fall in the number of mesothelioma deaths at 35-49 years of age in British men (289 in 1990-1994, 122 in 2000-2004), although less in women (56 in 1990-1994,39 in 2000-2004). Earlier case-control studies have used hospital-based controls or relied on next-of-kin interviews and most involved small numbers of cases (Muscat and Wynder, 1991; Howel et ai, 1997; Teschke et aI, 1997; Iwatsubo et ai, 1998; Agudo et ai, 2000; Rodelsperger et aI, 2001). We carried out the first populationbased study in Britain of the relationship between mesothelioma risk and lifetime occupational and residential history of asbestos exposure obtained at interview, and the largest worldwide. The main aim was to estimate risks and numbers of cases caused by specific occupational and environmental exposures. The results are particularly relevant to developing countries where unconcroIled asbestos exposure is still common. "Correspondence' Professor J Peto: E-mail: Julian.Peto@lshtm ac.uk Received 30 September 2008; reVised 15 December 2008: accepted 15 December 2008; published onltne 3 March 2009 MATERIALS AND METHODS Mesothelioma patients in England, Wales and Scotland born since 1925 were identified through chest physicians, surgeons and nurses, the National Cancer Research Network, and English and Scottish hospital records. A small proportion was identified through cancer registries and other sources. Population controls were selected at random from a 1 in 300 sample from Health Authority registers (now Primary Care Trusts), frequency matched by 5-year age group and sex. Owing to fears oflegalliability under confidentiality and data protection law, no data were provided by any of the Health Boards in Scotland, 11 Health Authorities in England and 3 in Wales. Up to six randomly selected age-matched GP controls were approached for each interviewed mesothelioma case in these areas. The study was approved by the South Thames MREC. Overall 39% of 1396 notified mesothelioma patients (423 too ill or dead, 87 no GP or consultant permission and 31 ineligible or not traced) and 18% of 2897 controls (169 too ill or dead, 169 no permission, 191 ineligible or untraced) were not invited for interview. The proportion of those invited who were interviewed, sometimes after several reminders, consisted of 73% (624 out of 857) of mesothelioma cases and 60% (1420 out of2368) of controls. As expected, response rates in controls were higher in more affluent areas {69% in the top two quintiles of socioeconomic status and 46% in the lowest}. There was no evidence that construction workers were under ascertained, with 8.3% of controls classified as working in skilled construction and building trades and 1.8% as carpenters, compared with 2001 census proportions of 6.5 and 1.7%, respectively. The study was initially restricted to cases born since 1940, later extended to 1925, to include those aged up to 80 years. This resulted in a higher 1176 Table I UK mesothelioma case-control study C Rake er 01 Interviewed mesothelioma cases and controls by Job categolY and all Bntlsh mesothelioma deaths, by year of birth and sex Mesothelioma cases Population controls National mesothelioma register 2000-2004 Ever worked Never worked Ever worked Never worked Central in high-risk in high-risk in high-risk in high-risk Year of birth age" jobsb jobs Total % jobsb jobs Total % n % lv1ale cases ;.1965 35 I 1960 1964 40 4 1955 1959 45 11 1950 1954 50 42 1945 1949 55 105 1940 1944 60 145 1935-1939 65 82 1930-1934 70 48 1925-1930 75 36 I 2 0.4 I 0 4 0.8 5 2 13 2.5 20 2 44 8.6 66 14 119 23.2 162 10 155 303 252 7 89 17.4 97 49 9.6 52 37 72 44 3 3 03 3 01 7 13 I.", 14 02 16 36 32 48 08 45 I11 100 166 29 123 285 256 524 9.0 128 380 34 :' 893 153 ,6 143 12 q 1223 2:.0 27 79 7 1~20 244 18 62 5.6 1529 263 Total 474 Female cases ~ 1965 35 0 1960 1964 40 0 1955 1959 45 I 1950 1954 50 2 1945 1949 55 6 1940 1944 60 13 1935 1939 65 8 1930-1934 70 5 1925-1930 75 2 38 512 100.0 699 2 2 1.8 0 I I 0.9 2 7 8 73 I 5 7 6.4 7 1I 17 155 9 21 34 30.9 17 17 25 22.7 22 7 12 10.9 9 2 3.6 4 413 1112 1000 5820 1000 0 0 5 06 4 6 1.9 5 C.6 13 14 45 23 26 13 20 6.5 31 3.4 45 54 175 86 95 75 92 299 162 180 55 77 250 181 20 I 21 30 97 178 198 11 15 41 230 255 Total 37 73 110 100.0 71 237 308 1000 901 1000 'In all. 97% (60 lout of 622) of cases were diagnosed between 2000 and 2004 bEver worked ,n Job categones I- 5: nOIHonstructlon hlgh-rs~. Clrpenter. p.umber lelect'1C1al'/ painter, other construction and medium-risk Industnal jobs. 'Worked only in low-nsk Industnal or non-industnal Jobs proportion of younger cases than seen nationally (Table 1). Histological confirmation was obtained for 92% of interviewed mesothelioma cases. Interviews were conducted between January 2001 and June 2006. Cases and controls were ineligible if they were physically or mentally unfit for interview, without access to a telephone or unable to speak English. All eligible patients were sent a preinterview postal questionnaire requesting lifetime occupational and residential history. This formed the basis for the structured telephone interview, which also included questions on smoking history, DIY activities and other possible environmental exposures. Cases were asked about various asbestos exposures in each job, depending on the type of work. These included work with AIB, lagging, sprayed coatings, cement, insulation, heat-protection materials, gaskets, textiles and brake linings. For each job, the duration, description and occupational code were recorded, together with frequency of direct or bystander asbestos exposure. Statistical methods Odds ratios (ORs) adjusted for 5-year period of birth and socioeconomic status (quintile of Townsend score from 2001 census data linked to postcode) were estimated by unconditional logistic regression analysis using STATA (StataCorp, 20(7). Occupational histories were truncated in 1992. Occupations were assigned to risk categories primarily on the basis of proportional mortality ratios (PMRs) for mesothelioma (McElvenny et ai, 2005). Non-construction high-risk occupations (most with PMR> 200) included asbestos factory workers, laggers, shipbuilding and dockyard workers, naval personnel, and others working on board ships. Preliminary analysis showed that the risk was highest for carpenters and higher for plumbers, electricians and painters than for other construction workers. All other jobs were classified on the basis of Standard Occupational Classification (1990) code and main place of work as medium-risk industrial (primarily occupations with PMR> 100, including mechanical and electrical process and assembly workers, welders, railway workers, surveyors, inspectors and industrial scientists), low-risk industrial (including motor mechanics, draughtsmen, warehousemen, drivers, plant and machine operators and armed forces) or non-industrial. Substantial asbestos exposure was defined as working with or disturbing AIB, sprayed coatings, lagging, other asbestos insulation or raw asbestos. Cases were thus classified into eight mutually exclusive exposure groups based on their highest exposure category irrespective of duration. These were ranked as (1) highrisk (including lagging and shipbuilding but excluding construction), (2) carpenter, (3) plumber, electrician, painter, (4) other construction, (5) medium-risk industrial, (6) substantial asbestos exposure in a low-risk occupation, (7) living with an occupationally exposed relative and (8) the remainder, comprising 52 cases (18 men, 34 women) and 439 controls (289 men, 150 women) with none of these exposures. Men who worked only in low-risk industrial or non-industrial jobs (groups 6, 7 and 8) constituted the reference group for the occupational analyses in Tables 3- 5. Univariate analyses of domestic and neighbourhood exposures and work with other asbestos products (heat-protection materials, gaskets and brake linings) were restricted to cases who had only done low-risk industrial or non-industrial work not involving substantial exposure (groups 7 and 8). Possible nonoccupational hazards included living with an asbestos worker or in a council property, prefab or high-rise block, living near a potentially hazardous site (asbestos factory or disposal site, power plant and Bntrsh Journal of Cancer (2009) 100(7), I 175 - I 183 ~ 2009 Cancer Research UK shipyard) and DIY involving asbestos. A full report giving details of the occupational classifications and subgroup results will appear on the Health and Safety Executive's website (www.hse.gov.uk). Lifetime risks in men were calculated from ORs as LR =OR x A -,- B, where A is 0.590/0, the predicted lifetime mesothelioma risk in British men born in the 1940s (Hodgson et ai, 2005), and B is the weighted average OR in male controls. B equals 7.4 in Table 6, where the reference group is unexposed, and 5.0 in Tables 3-5, where the reference group includes men who reported domestic exposure or substantial occupational exposure in low-risk jobs. RESULTS occupational exposure Those interviewed (622 mesothelioma cases and 1420 controls) are shown by sex, period of birth and exposure category (ever/never worked in job groups 1- 5) in Table 1. The occupational analyses in Tables 2 - 5 are restricted to men. Figure 1 shows the proportions of male cases and controls beginning a new job in each period since 1940 who reported asbestos exposure in that job. Jobs of more than 5 years duration are excluded to ensure that reported exposure is representative of the period when the job started. The frequency of exposure fell sharply during the 1970s, and the heaviest exposures (sawing AIB or applying lagging or sprayed coatings) had virtually ceased by 1982. The left-hand part of Table 2 shows ORs for male mesothelioma cases and controls who worked for at least 5 years in each main job group. Forty-six of the 102 non-construction high-risk mesothelioma cases had worked in docks, shipyards or on non-naval ships, and 26 in the Navy. The reference group in Table 2 comprises 25 cases and 278 controls with no high- or medium-risk or construction work and less than 5 years in low-risk industrial occupations. Carpenters suffered the highest risk (OR 36.0, 95% confidence interval (Cl) 19.2- 67.3), followed by all non-construction high-risk jobs (OR 16.8, 95% Cl 9.6-29.3), plumbers, electricians and painters (OR 14.6, 95% Cl 8.8-24.4) and other construction workers (OR 7.9, 95% Cl 4.7 -13.3). The overall OR for 5 or more years in any medium-risk industrial job was 5.2 (95% Cl 3.3 -8.2). The right-hand part of Table 2 shows the corresponding ORs for men who never worked in any higher risk category. The ORs for construction and medium-risk industrial workers remain high when those with higher risk occupations are excluded. In contrast, the OR for low-risk industrial occupations falls from 4.1 (95% Cl 2.6-6.4) overall to 1.1 (95% Cl 0.5-2.2) UK mesothelioma case-control study C Rake et aJ when those who had also worked in medium or higher risk jobs are excluded. Table 3 shows ORs for men ever employed as carpenters (lower part) or in at least one high-risk, construction or medium-risk job (upper part) by age starting the first such job and duration of relevant employment. The OR in men first exposed before the age of 20 years is 13.4 (95% Cl 9.2 -19.6) for 20 or more years of any high-risk work, and 99.7 (95% Cl 43.7 -227.5) for 20 or more years as a carpenter. Analyses of duration before and after 30 years of age for all high-risk work (Table 4, upper part) and for carpentry (lower part) show a strong trend in OR with increaSing duration only before 30 years of age. Odds ratios are consistently lower in each row in men who stopped exposure before 30 years of age, but there is no evidence of increasing risk with longer duration after 30 years, and the OR for men first employed in any high-risk job after 30 years was only 1.7 (95% Cl 0.7-3.9). In Table 5, men are assigned to the five occupational groups on the basis of the highest category in which they ever worked (see Materials and Methods). As in Tables 3 and 4, ORs are relative to men employed only in low-risk industrial or non-industrial jobs. The ORs and corresponding LRs for 10 or more years of relevant work before 30 years of age were highest for carpenters (OR 50.0, LR 5.9%), about one-third as high for electricians, plumbers and painters (OR 17.1, LR 2.0%) and for non-construction high-risk jobs (OR 15.3, LR 1.8%), and lower for other construction workers (OR 7.0, LR 0.8%) and for all medium-risk industrial jobs (OR 5.2, LR 0.6%). Odds ratios for all men in each category irrespective of duration are also shown, ranging from 23.3 for carpenters to 2.8 for medium-risk industrial workers. The nature and frequency of reported substantial asbestos exposure were also predictive, with higher risks in each category in men reporting frequent direct exposure, but the OR was still significantly increased within each of the five exposure categories (Table 5) among men who did not report direct or indirect substantial exposure in any job before 30 years of age. The proportion of controls reporting direct exposure before 30 years of age was 67% (28 out of 42) among carpenters, 55% (63 out of 114) among plumbers, electricians and painters, 26% (37 out of 142) among other construction workers, 12% (32 out of 263) among medium-risk industrial workers and 3% (12 out of 413) among low-risk workers. 1177 Non-occupational exposure The reference group in Tables 3- 5 included 33 men (7 cases, 26 controls) who reported substantial asbestos exposure in low- Table 2 Numbers of male mesothelioma cases and controls who worKed for at least 5 years before 1992 In each occupatlor,al category Occupational category Cases Controls OR (95% Cls) Cases Controls OR (95% Cls) Non constructIOn high nsk Any non-construction hlgh-nsk job 102 78 168 (96, 29.3) Co~structlon Carpenter 93 Plumber, electnClan, palntel- 01 decorator 115 Other construction 81 No other high-fisk work 36 360 (192. 673) 81 30 96 14.6 (88, 244) 99 82 120 7.9 (47, 133) 59 101 393 (202,765) :4,8 (87, 25.1) 68 (40. i 17) Medlum-nsk Industnol Any med,um-nsk Industnal Job No high-risk or construction work 157 331 5.2 (3.3, 8.2) 57 201 32 (I 9, 53) Low nsk II1dustr/n/ Any low-nsk Industnal job Reference group' No hIgh fiSk. COIlStl"~CtIOI1 or medium rISk work 153 406 4.1 (26. 6.4) 13 135 I I (0.5, 22) 25 278 1.0 (ref) 25 278 10 AbbreViat,ons' Cl = confdence Interval: OR = odds ratio Men With dny exposure In preceding occupational categones are excluded III the ngh'-~dnd pall of :he :allle 'The reference group worked only ,n non-!l.dustndl jobs or In Iow-risk industrial Jolls for less than 5 years ~ 2009 Cancer Research UK Bntlsh Jouma; of Cancer (2009) 100(7) 1175--1183 1178 Table 3 UK mesothelioma case-control study C Rake er of Odds ratios for male cases by age started and total duration In hlgh-nsk" occupations and In carpentry Duration of employment <5 years 5-9 years 10-19 years :;;,20 years Total Age at first job Cases! of this type controls All high t1sk Jobs" OR (95% Cl) Casesl controls OR (95% Cl) Cases! controls OR (95% Cl) Casesl controls OR (95% Cl) Casesl controls OR (95% Cl) <20 20-29 :;;,30 Total 27/75 7/41 5/15 39/131 40 (2.3, 6.9) I 8 (0.8, 4.4) 36(12,10.4) 3.2 (2.0, 53) 36/77 3/16 0/6 39/99 5.2 (3.1, 8.7) 2.0 (06, 7.3) 0.0 (0.0, 7.1)" 43 (2.6,72) 51/93 7/37 2/23 60/153 5.9 (3.6, 96) 2.1 (09,50) 1.0 (02, 43) 4.2 (27, 6.6) 311/265 24/46 115 336/316 I 3.4 (9.2, 19 6) 55 (3.0,10 I) I 8 (0.2, 16 3) ,2.1 (83, 17.6) 425/5,0 411140 8/49 474/699 92(6.4,131) 3 (19.50) I 7 (0.7, 39) 73 (5 I. 104) Carpentry <20 ;;,20 Total 75//94 29130 ((34..08,.9236.44)) 261/73 190.30 ((31..40,, 6313 9I)) 134/6/5 358.59((11324.2,14252.)1) 6351/510 9191..70 ((2493,7.4212.17)5) 91051/138, 318000 ((246..3,21679.)5) 12113 110 (4.5. 270) 8/10 92 (33, 259) 17/11 18.5 (7.8, 44.1) 68115 625 (30.9.1265) 105/49 265 (159.442) AboI"Cvlatlons Cl = "High risk Incudes confidence Interval, OR = odds rat,o. lob categories 1- 5. non-construc Odds ratios are relative to the 38 cases and 41 3 controls With no h'gh-nsk construction or mcdlJm-nsk ndustr'dl jobs Comfield confidence Interval f.on hlgh-nsk, carpenter, plumber/electnClan/pdlnter. other construction and med'uf'l-ns< Industrial :ODS ",Jnadjusted Table 4 Odds ratios for male cases by duration of employment In hlgh-nska occupations and in carpently before and after 30 years of age Duration after 30 years of age None < 10 years ;;, 10 years Total Duration before 30 years of age Ai! hfgh-rysk Jobs None < 10 years ~ 10 years Total Casesl controls 59/163 19131 78/194 OR (95% Cl) 39 (2.5. 6.1) 6.8 (35. 13.3) 4.4 (28, 6.7) Cases! controls OR (95% Cl) 5/21 27176 54/53 861150 25 (0.9, 6.8) 39 (22, 6.8) 11.5 (69,19.1) 62 (4.1, 96) Cases! controls OR (95% Cl) 3/28 47/ I04 260m3 310/355 1.1 (0.3,38) 4.7 (29,77) 13.1 (8.9. : 9 3) 9.6 (66, 14.0) Casesl controls 8/49 133'3 4 3 333 /307 47";'699 OR (95% Cl) i 7 (07, 39) 4.1 (28,6.1) 2 I (84, 176) 73 (51.104) Corpentry None < 10 years ;;, 10 years Total Abbrevlat,ons. Cl = aHigh nsk Includes 16/16 7/3 23119 confidence Interval, job categones I - 5 114 (5.1, 25.6) 26.3 (6.3, I 09 7) 134 (6.5, 27.6) OR = odds ratio. non-construction 3/7 6i1 1212 2,/10 6.5 (i.5, 28.0) 58.3 (6.4, 532.1) 93.1 (18.9, 458.3) 28.1 (i 1.6, 678) 2/4 8/6 51110 61120 70 (I 2, 42.2) 15 I (48,47.2) 73.8 (32.3, 168.9) 409 (21 3, 78 8) 5111 30,23 70; IS 105/4 9 66 (2.1. 21 0) I<f 6 (7.6, 283) 663 (32 S. i 35 5) 265 (159,442) Odds ratios are relative to the 38 cases and 41 3 CDntrols w,th no h,gh-nsk construction er nlcdlum-nsk Industnal jobs hlgh-nsk, carpenter, plumberle,ectnClan/palnter. other construction and medILm-r.sk Industrd, Jobs risk occupations. These were excluded in univariate analyses of other and non-occupational exposures, which were restricted to men (31 cases, 387 controls) and women (71 cases, 236 controls) who reported no high- or medium-risk work and no substantial exposure in any job. Other potential asbestos exposures at work were not associated with significantly increased risk, although few were reported. These induded vehicle maintenance involving work with brakes or gaskets (OR 0.4, 95% cr 0.1- 1.7), asbestos present at the workplace (OR 0.8, 95% Cl 0.5 -1.5), construction work at the workplace (OR 1.4,95% Cl 0.8 -2.3), working in or near a ship- yard or construction site (OR 1.3,95% cr 0.3 -6.1) and any other reported asbestos exposures at work (OR 1.6,95% cr 0.7-3.6). The only significant non-occupational association was living with a potentially exposed worker before 30 years of age (OR 2.0, 95% Cl 1.3-3.2). The OR for living within a mile of a potential source before 30 years of age (asbestos factory or disposal site, shipyard or power plant) was 0.6 (95% Cl 0.2 - 2.0). The OR for any type of DIY activity was 0.7 (0.4- 1.2), and no subgroup of DIY activity by frequency or possible asbestos exposure suggested any excess. No type of housing was significantly associated with risk (prefab, council or former council, high rise or any asbestos in the building). The OR for current smokers compared with nonBnt.sh Journal of Cancer- (2009) 100(7), J 175 - , 183 asmndok1e.2rs(9w5a%s c1.r5 0(.995-%1.6c)ro0v.e8ra-2ll..7) in this unexposed subgroup, Asbestos-related and background cases All men and women are shown in the eight non-overlapping exposure categories (see Materials and Methods) in Table 6. Cases are classified by their highest exposure, so the groups are mutually exclusive, The reference group for this analysis comprises the 52 cases (18 men, 34 women) and 439 controls (289 men, ISO women) with none of these exposures. Five of the 110 female cases reported high-risk work (OR 4.8, 95% er 1.3 - I7.7). A further 32 female cases had done medium-risk industrial work (OR 2.4, 95% Cl l.3-4.3), the majority (88%) as assemblers or routine process operatives. The risk was also increased in those who worked only in low-risk jobs but reported a substantial asbestos exposure (seven male and two female cases: combined OR 3.8,95% Cl 1.78.8). The ORs for domestic exposure before 30 years of age in Table 6 (2.1 tor men, 1.9 for women; combined OR 2.0, 95% Cl 1.3-3.2) are based on cases with no occupational exposure. Logistic regression analysis in all cases, adjusting for duration and main exposure group, gave an OR for domestic exposure before 30 :~ 2009 Cancer Research UK UK mesothelioma case-control study C Rake et of Table 5 Odds ratios for male cases by durdtion of employment before 30 years of age for Job categolY and reported asbestos exposure Duration in job category before 30 years of age None Casesicontrols OR (95% Cl) < 5 years Cases/controls OR (95% Cl) 5 9 years Caseslcontrols OR (95% Cl) ;, 10 years Cases/controls OR (95% Cl) Non-construction high risk Carpenters 4/15 2.8 (0.9, 8.9) 3/10 3 I (0.8, 118) 52/59 9.8 (5.9. 162) 9112 8.2 (3.2, 209) 42125 18.3 (10.0,33.7) 1115 24.4 (8.0, 749) 55/39 15 3 (9.0. 26.2) 66115 50.0 (25.8, 96.8) Construction Plumbers, electricians, painters Other construction 6/12 5.2 (1.8, 14.9) 7124 3.2 (I 3, 8 I) 13134 40 (19, 8.3) 20/66 13 (1.8, 6.0) 24/22 123 (6.3, 24.2) 12/30 4.3 (20,90) 69146 I7.1 (1003, 28 3) 13/22 7.0 (3 2, 15.2) All other jobs Medium-risk industrial Low risk (reI) 'i/26 15 (05,46) 15/79 2 I (I .,40) 8168 12 (06,28) 4/90 52 (3 i, 8.5) Lifetime nsk for ;, 10 yeal'S 1.8% 5.9% duration" 20% 0.8% 06% 012% 1179 Reported asbestos exposure before 30 years of age" None Caseslcontrols OR (95% Cl) 29/56 55 (31,97) Indll-ectC <5 years Cases/controls OR (95% Cl) ;,5 years Cases/controls OR (95% Cl) 5/14 4.0 (I 3, I I 7) 23/11 21 7 (9.7, 48.5) 12112 9.8 (4.1, 23.5) 211 168 (14, 1960) I11 10.2 (0.6, 171.2) 16/38 4.4 (2.2. 8.7) 2/4 5.0 (09. 28.9) 1519 183 (74, 44.9) 23/91 27 (1.5, 4.8) 35202 19 (I :,3 I) 4/6 7.6 (2.0, 28.5) 418 61 (17,214) 4116 25 (0 a, 79) 6113 47 (I 7, 132) 33/393 I11 117 Direct mtreqd <5 years Caseslcomrols OR (95% Cl) ;;:5 years Caseslcontrols OR (95% Cl) 10/6 IBO (6 I. 53.2) 20/16 135 (64, 285) I 1111 12.1 (4.9,300) 321B 49.6 (21.1, 116.4) 5119 2.9 (1.0, 8.2) 39/25 17.4 (9 5, 32.0) 2/7 .:8 0/4 3.0 (0 6, 15 I) 12(0 ,9.8) 8117 11, \8 1f7 5.5 (2.2, 13 6) 69 (30.158) Direct freqP <5 yeal'S Cases/controls OP. (95% Cl) ;;.5 years 26/13 22.3 (10.5, 474) 1214 32.0 (9.7, 1055) 617 9.5 (3.0, 29.9) 4/7 2/1 III 6.4 (1.8, 23.0) 22" (I 7, 261 3) Casesl commis OR (95% Cl) 40122 19/5 29/12 7/6 915 1i0 19.2 (10.2. 36.1) 38.4 (135, 109.6) 275 (12.9. 586) 110 (34, 349) 20.7 (65, 655) Ever worked '11 Job category Cases/controls OR (95% Cl) 153/138 I 1.9 (7.9, 18.0) 89/42 233 (141, 38.5) 1121114 10.8 (7.1,16.5) 521142 4.0 (25,64) 681263 28(1843) 38/413 IC(rei) Abb,levlatJons Cl = contidence Interval. OR = odds ratio 90 = OR x 0 ;'9% - 5 O. Sec statistical methods. bTyp Cases who ever worked In each lob category are excluded In subsequent co'umns "ProJected lifetime nsk to age these are coded h,erarchlcally. 'Work done by someeonaend,ndtuhreat.soanmoefaarsebaes"twosoerxkpdoosunree tIhneamnsyelJvoebsclaetsesgothryan. Gornocuepspearrlewmeeukt.ua""Wy oerXkCldUoSnivee tthhaemt .sse.lfvseesvcarta,leeaxstpowseuelk'clsy occur, years of age of 2.3 (95% cr 1.5 -3.8) in women, significantly higher than the OR of 1.1 (95% Cl 0.9-1.4) in men. Similar analyses based on the type of relative, irrespective of age, gave a combined estimate of 1.3 (95% Cl 1.0 -1.6) for living with a high-risk parent or sibling and an estimate of 2.1 (1.3-3.5) for living with a highrisk spouse. The latter was based largely on women, as only two male cases and one male control reported living with a high-risk spouse. Of controls, 20% reported living with a high-risk parent and 120/0 with a high-risk sibling, and 20% of female controls had lived with a high-risk spouse. Table 6 shows the attributable fraction of cases in each category, ranging from 97% (86.4 out of 89) among male carpenters to 49% (24.3 out of 50) in men and women who lived with an exposed worker before 30 years of age. In all, 85% (435.6 out of 512) of male and 22% (24.5 out of 110) of female cases are attributed to occupational exposure, and a further 1.3% (6,8 out of 512) of male and 16% (17.5 out of 1I0) of female cases had no occupational exposure but were attributed to living with a high-risk worker. The total number of unattributed 'background' cases is 69.6 in men and 68.0 in women, '1'; 2009 Cancer Research UK Br;tlsh Joumal or Cancer (2009) 100(7), I 175 - I 183 1180 45 UK mesothelioma case-control study C Rake er 01 40 35 Cases Controls 30 25 ~/~ 20 15 10 / All asbestos exposures 4' . . . . . . . . \ ,, . 5 ~ .. , . , ..... . 0 1940 1943 1946 1949 1952 1955 1958 1961 1964 1967 1970 1973 1976 1979 1982 1985 1988 1991 1994 1997 Cases' 15 34 38 48 73 121 133 178 173 166 143 127 110 89 80 73 61 56 50 72 Controls. 18 39 67 93 130 187 292 301 326 313 287 257 204 167 130 140 144 99 102 172 Year starting Job (3 year penod) Figure I Proportion of all men reporting asbestos exposure by year starting new Job Table 6 Mesothelioma cases In men and women attributed to asbestos exposure in each exposul'e categolY Male cases Female cases Cases Cases Attributed to this exposure Attributed to this exposure Highest exposure category OccupctJonol exposure Non-construction high fisk Carpenters Plumbers. electriCians and painters Other construction Medlum-nsk Industlial Othel' subS+u1ntlal exposure Yes No Total Controls OR (95% Cl) Yes No Total Controls OR (95% Cl) 1443 87 153 138 17.5 (10.3. 29.8) 4.0 1.0 5 5 48 (I 3,177) 86.4 2.6 89 42 34.2 (187. 626) 0 0 105.0 7.0 112 114 159 (92. 273) 0 2 43.2 88 52 142 59 (33. 10.5) 0 I 514 16.6 68 263 4 I (24.7.2) 187 13.3 32 63 24 (I 3. 43) 5.3 1.7 7 26 4.2 (I 6. 109) 1.8 0,2 2 I 9.6 (0.8, I 12.3) Non-occupational exposure DomestiC exposure before 68 62 30 years of age None of the above (reference) 18.0 13 98 21 (1.0.4.5) 175 195 18 289 1.0 34.0 37 86 19 (I 1,32) 34 150 10 Tota, 442.4 69.6 512 1112 7.4b 42.0 68.0 110 308 I 6~ AbbreVIations Cl = confdence Interval; OR = odds ratIo Cases .n each row are excluded ,n subsequent rows aNumber not dttnbuted to expos~rEc = tota c,b"s/OR bAve'-age of ORs weighted by nurrber of contr 015 In each row. DISCUSSION Proportional mortality ratios for mesothelioma based on last fulltime occupation as recorded on death certificates (McElvenny et ai, 200S) provide the only estimates of occupational mesothelioma risks in Britain. The risk depends mainly on asbestos exposure below 30 years of age, however (Tables 3 and 4), and our study provide the first overview of the distribution of risk in the British population, the extraordinary risks suffered by men who did the most dangerous jobs when they were young and the contribution of environmental exposure, particularly to the families of exposed workers. Recall bias was minimised by structured questions about specific exposures, and our main analyses were based on job title, which should be less liable to Bntlsh Joumal of Cancer (2009) 100(7). I 175 - 1183 ~ 2009 Cancer Research UK differential response by cases than reported asbestos exposure. The value of lifetime job histories is illustrated by men who had worked for at least 5 years in low-risk industrial occupations; their ORs fell from 4.1 (95% Cl 2.6-6.4) to only 1.1 (95% Cl 0.5-2.2) when those who had also done more hazardous work were excluded (Table 2). Among motor mechanics, for example, only 2 of 18 cases compared with 23 of 54 controls had never worked in other more hazardous occupations. Of male mesothelioma cases, 94% (481 out of 512) and 65% (725 out of 1112) of male controls had worked in a hazardous occupation (Table 6), implying an attributable fraction of 85%. The predicted lifetime mesothelioma risk for British men born in the 1940s who did more than 10 years of relevant work before 3C years of age is 5.9% for carpenters, 2.0% for plumbers, electricians and painters, and 0.8% for other construction workers (Table 5). The LR is 1.8% for all high-risk non-construction occupations, but this is a broad category that includes many subgroups with substantially higher risks. Table 2 shows their overall OR for 5 or more years' work, which was 16.8 (95% Cl 9.6-29.3), but the OR for metal plate workers (mainly shipbuilders) was 43.3 (95% Cl 13.5-138.6). Although this is the largest published study of mesothelioma risk in relation to lifetime occupational history, much larger numbers would be needed to provide reliable estimates for individual occupations. The proportion of men who had ever worked in carpentry was 4% of controls and 21% of mesothelioma cases (Table 4: 49 out of 1112 controls, 105 out of 512 cases), and 33% (10 out of 30) of mesothelioma cases in men born since 1950 who started work in 1970 or later, so the predicted eventual total of 90000 mesothelioma deaths in both sexes in Britain by 2050 (Hodgson et ai, 2005) will include about IS 000 former carpenters. The excess lung cancer risk in heavily exposed workers is likely to be of the same order as the mesothelioma risk (Darnton et ai, 2006), so more than 1 in 10 of all British carpenters born in the 1940s may die of a cancer caused by asbestos. A substantial proportion of these deaths will be among those who installed AIB as fireproofing required under building regulations (HMSO, 1965) and these will far exceed any possible benefit of such work to the public. The large amount of asbestos that remains in many older buildings is still a potential hazard to construction workers involved in renovation, maintenance or asbestos removal. The risk to carpenters is particularly high in Britain, and also in Australia (Yeung et ai, 1999). Most studies in other countries reported higher risks in plumbers, electricians and other construction workers than in carpenters (Muscat and Wynder, 1991; Teschke et ai, 1997; Rodelsperger et aI, 2001). Among construction workers, preliminary results of a French populationbased case-control study show the highest risks in plumbers, pipe fitters, structural steel workers and construction labourers (Goldberg et ai, 2006). In a large non-interview study in California based on main occupation of over 2000 mesothelioma cases and pancreatic cancer controls, increased ORs were seen for plumbers (OR = 4.9,95% Cl 2.8 -8.3), electricians (OR = 3.8,95% Cl 2.0, 7.1) and painters (OR=2.6, 95% Cl 1.3-5.3) but not for carpenters (OR = 1.2, 95% Cl 0.8 -2.0) (Pan et ai, 2005). The ORs ",1thin each occupational exp05ure category were lower but still substantially increased even in men who recalled no substantial asbestos exposure, suggesting that many were exposed indirectly or could not identify the asbestos materials they handled. Most people report their own and their parents' occupations correctly many years later (Berney and Blane, 1997), but recall of past asbestos exposure shows poor reproducibility at re-interview (Holmes and Garshick, 1991). A recent study of plumbers showed that many do not recognise the friable asbestos materials that they still sometimes encounter (Bard and Burdett, 2007). The increased risk for medium-risk industrial work reflects widespread and often unrecognised contact with asbestos in metal working, electrical trades and assembly line work. A large UK mesothelioma case-control study C Rake et 01 118 i proportion of the British population worked in these sectors (24% of male and 20% of female controls). There were too few occupationally exposed female mesothelioma cases to estimate risks reliably, but Table 6 suggests that workplace exposure caused about 22% (24.5 out of 110) of all female caSes. The occupational hazard in women was concentrated in medium-risk industrial settings, particularly assembly line work. The only evidence of an occupational risk outside high- or medium-risk and construction occupations was the seven men and two women who reported substantial personal or bystander exposure III other occupations (Table 6). Non-occupational exposure The only substantial risk factor in those with no direct occupational exposure was living with a high-risk worker, a hazard that has been recognised for many years (Newhouse and Thompson, 1965; Vianna and Polan, 1978; Joubert et ai, 1991; Bourdes et ai, 2000; Magnani et aI, 2001). The excess risk, which was confined to those who lived with an exposed worker before 30 years of age and was similar in men and women (combined OR 2.0, 95% Cl 1.3 - 3.2), corresponds to an increase in LR of about 1 per 1000. There was no overall risk in men and women who reported living within a mile of a potential environmental hazard (asbestos factory or disposal site, shipyard or power plant) before 30 years of age, although the risk was non-significantly increased in those who lived near one of these potential sources for 20 or more years (OR 3.3,95% Cl 0.7-14.8, based on three cases and six controls). We had no means of identifying sites that produced substantial local exposure. There was certainly some hazard to residents around a few factories in the past (Newhouse and Thompson, 1965; Magnani et ai, 2001), but no risk was seen around others (Hammond et ai, 1979), and many apparently environmental cases are related to occupational exposures (Arblaster et ai, 1995). There was no significant difference between current smokers and lifelong nonsmokers either in this apparently unexposed subgroup (OR 1.5, 95% Cl 0.8 - 2.7) or overall (OR 1.2, 95% cr 0.9, 1.6). The unattributed cases in each row of Table 6 are presumably due to ambient or unreported asbestos exposure or to other or natural causes. This unexplained risk is similar for non-industrial (including retail, office, educational, health-care and agricultural) and low-risk industrial work, and corresponds to a predicted LR of 0.08% in men. The analysis of attributable risk in Table 6 indicates that these background cases accounted for 69.6 (14%) of the 512 male and 68.0 (62%) of the llO female mesothelioma cases. The same analysis restricted to cases born during 1940 -1949 also gave similar male and female estimates for the number of unattributed cases (31.9 out of274 in men and 36.7 out of 51 in women). Table 1 shows that the male/female ratio of interviewed cases born during 1940-1949 (5.4: 1) was close to that of all British mesothelioma deaths during 2000 - 2004 among those born during 1940 -1949 (5.7: 1). The annual number of unexplained mesothelioma cases is thus similar in men and women, and corresponds to a LR of the order of 1 per 1000 among Britons of both sexes born in the 1940s. The cumulative female mesothelioma death-rate by age 70 is now more than three times higher in the UK (0.037%) than in the US (0.012%). If this is due to differences in asbestos exposure, more than two thirds of mesotheliomas in British women born since the 1930s are caused by asbestos, far more than the 38% (Table 6: 42.01110) that were attributed to identified exposures in our study. A similar conclusion is suggested by the three-fold increase in the death-rate in British women between 1975-1979 and 2000-2004. This would imply that at least 30% of female cases (of the order of 100 per year) are caused either by environmental asbestos exposure or by occasional or ambient exposure in occupational settings that we have classified as low risk. If so, there is presumably a similar number in men. Many apparently spontaneous mesotheliomas are therefore likely to be due to an :9 2009 Cancer Research UK Bntlsh Joumal of Cancer (2009) 100(7), I 175 - I 183 UK mesothelioma case-control study C Rake er 01 1182 increase in ambient asbestos exposure that coincided with the widespread occupational exposures of the 1960s and 1970s. Future trends The upper part of Table 4 shows that high- or medium-risk exposure beginning after 30 years of age did not cause a statistically detectable increase in risk. Among men already exposed for 10 or more years before 30 years of age, however, a further 10 or more years of exposure after 30 years of age increased the OR from 6.8 to 13.1 for all high-risk work. The estimated factor is 2.1 (95% Cl 1.1-4.0) in an analysis restricted to these two subgroups, suggesting that at 30 years of age, the mesothelioma risk is still increased substantially by continuing asbestos exposure. The future burden of mesothelioma is thus still uncertain. The death rate in men born around 1945 is higher up to 55 years of age than in any earlier or later birth cohort, but few had substantial asbestos exposure after 30 years of age, and we still do not know how rapidly their mortality will increase at older ages. Contribution of amosite The mesothelioma risk caused by amosite (brown asbestos) is two orders of magnitude greater than that by chrysotile (white asbestos) (Hodgson and Darnton, 2000), and it seems likely that a major cause of the extraordinary risk to British carpenters was cutting amosite board with power tools, which was widespread in the UK construction industry through the 1970s and continued into the 1980s. A comparison of current mesothelioma death rates and imports to the US (Virta, 2006) and UK (MRC Institute for Environment and Health, 1997) of white, brown and blue (crocidolite) asbestos also suggests that the much higher mesothelioma death-rate in the UK was caused by its much greater use of amosite. The mesothelioma death-rate in men aged 45-49 is now more than three times higher in the UK than in the US (US: 0.26 per 100000 in 2000-2004, based on 139 deaths; UK: 0.87 per 100000 in 2001-2004, based on 66 deaths). These men were born between 1950 and 1959, and few would have had much asbestos exposure before 1970. The UK used slightly less chrysotiJe during the 1970s (2.4 kg per head in 1970, 1.7 in 1980) than the US (3.1 kg per head in 1970, 1.5 in 1980), and the UK had virtually ceased using crocidoIite by 1970, while US crocidolite imports increased from 8900 tonnes in 1970 to a peak of 16900 tonnes (0.08 kg per head) in 1978 and remained above 5000 tonnes per year until 1984. However, the UK imported far more amosite per head than the US in the 1970s. UK amosite imports were 21600 tonnes (0.4 kg per head) in 1970 and did not decline until after 1976, while US amDsite impDrts fell frDm 12900 tonnes (0.07kg per head) in 1970 to 1400 tonnes in 1976 (MRC Institute for Environment and Health, 1997; Virta, 2006). Australia's mesothelioma death-rates are similar to Britain's, and so were its patterns of amosite and crocidolite use (Leigh and Driscoll,2003). The UK cDntrol limit remained the same for amosite as for chrysotile (BOHS, 1973) until 1983, when it was reduced from 2 to 1 fm! 1 for chrysotile and from 2 tD 0.5 fml I for amosite. The 2 fml- 1 control limit was prDbably observed in most asbestos factories during the 1970s, and only four of the 512 male mesothelioma cases in our study had worked for mDre than 5 years in asbestos product manufacturing; but substantial asbestos exposure was widespread in the much larger workforce in construction. 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