Cancer Medicine
Open Access
ORIGINAL RESEARCH
Updated mortality study of a cohort of asbestos textile workers Enrico Pira1, Canzio Romano1, Francesco S. Violante2, Andrea Farioli2, Giovanna Spatari3, Carlo La Vecchia4 & Paolo Boffetta5 1Department
of Public Health Sciences and Pediatrics, Turin University, Turin, Italy of Medical and Surgical Sciences (DIMEC), Bologna University, Bologna, Italy 3Department of Environmental Science, Safety, Territory, Food and Health, Messina University, Messina, Italy 4Department of Clinical Sciences and Community Health, Milan University, Milan, Italy 5Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 2Department
Keywords Asbestos, cancer mortality, peritoneal cancer, pleural cancer Correspondence Paolo Boffetta, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York 10029, NY. Tel: +1-212-659-1474; Fax: +1-212-849-2566; E-mail: [email protected] Funding Information This work was supported by internal funds of the participating Institutions. Received: 2 May 2016; Revised: 15 June 2016; Accepted: 21 June 2016
Abstract Limited information is available on risk of peritoneal mesothelioma after asbestos exposure, and in general on the risk of cancer after cessation of asbestos exposure. We updated to 2013 the follow-up of a cohort of 1083 female and 894 male textile workers with heavy asbestos exposure (up to 100 fb/mL), often for short periods. A total of 1019 deaths were observed, corresponding to a standardized mortality ratio (SMR) of 1.68 (95% confidence interval [CI]: 1.57–1.78). SMRs were 29.1 (95% CI: 21.5–38.6) for peritoneal cancer, 2.96 (95% CI: 2.50–3.49) for lung cancer, 33.7 (95% CI: 25.7–43.4) for pleural cancer, and 3.03 (95% CI: 1.69–4.99) for ovarian cancer. For pleural and peritoneal cancer, there was no consistent pattern of risk in relation to time since last exposure, whereas for lung cancer there was an indication of a decline in risk after 25 years since last exposure. The findings of this unique cohort provide novel data for peritoneal cancer, indicating that – as for pleural cancer – the excess risk does not decline up to several decades after cessation of exposure.
Cancer Medicine 2016; 5(9):2623–2628 doi: 10.1002/cam4.824
Introduction The incidence of mesothelioma rises as function of the third or fourth power of time since first asbestos exposure (latency) [12], after taking into account time since cessation of exposure. The other determinants of mesothelioma incidence are average exposure to asbestos (linear relationship), and type of asbestos, with stronger potency of amphiboles than chrysotile [3]. The influence of other time- related aspects such as age at first exposure and duration of exposure appears to be largely or totally explained by latency [12]. These models linking asbestos exposure to mesothelioma incidence have been developed and validated mainly on the basis of results for the pleural form of the disease, since most available cohort studies include a small number of peritoneal mesothelioma [2].
Asbestos is also a cause of lung cancer, and cumulative asbestos exposure appears to be the main determinant of lung cancer incidence, together with the prevalence of tobacco smoking, because of the interaction between the two risk factors [3]. We reported the mortality follow-up to 2004 of a cohort of heavily exposed asbestos textile workers employed between 1946 and 1984, in which we observed 315 cancer deaths compared to 153.9 expected (standardized mortality ratio [SMR] 2.11; 95% confidence interval [CI]: 1.89–2.35), including 39 deaths from peritoneal cancer, 36 deaths from pleural cancer, and 109 deaths from lung cancer [14, 15]. In that analysis there was no difference in the SMR of pleural and peritoneal cancer between workers who had stopped exposure below age 30, and those who had continued exposure after age 40 [15].
© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
2623
Mortality of Asbestos Textile Workers
This cohort is unique since it contains a relatively large number of workers, in particular women, who experienced short-term, high-level exposure to asbestos. As discussed in detail in previous publications [14, 15], various types of asbestos were used in the factory, including crocidolite. Environmental exposure data were available between 1968 and 1977 [14, 17]. Average exposure levels as high as 100 fb/mL were measured in the opening and carding departments in the late 1960s; in the early 1970s average exposure levels were in the range 5–25 fb/mL, and in the late 1970s the average level was 2 fb/mL or less in all departments [14, 17]. The large number of deaths from peritoneal cancer is also an unusual finding. We decided therefore to update the follow- up of this same cohort to 2013, aiming for separate analyses for pleural and peritoneal cancer, as well as lung cancer, with focus on the pattern of mortality following cessation of exposure.
Materials and Methods Detailed information on the cohort is provided in previous reports [14, 15]. In brief, the cohort includes 1083 women and 894 men who had worked in an asbestos textile factory sited in Northern Italy, between 1946 and 1984. The main type of asbestos used in the plant was chrysotile, but crocidolite was also present, although the relative proportion of the two types of fibers over time is not precisely known. The current analysis includes 11 additional subjects as compared to the previous reports, who have been found to fulfill the inclusion criteria. For the present analyses, follow-up was extended to November 2013; subjects were censored when they reached 85 years of age, because of the possibility of misclassification of cause of death in the elderly. Therefore, end of follow-up was defined as date of death, date of last contact, date of 85th birthday, or November 30, 2013, whichever occurred first. We obtained employment data from personnel records at the factory, and ascertained vital status and causes of death through population registers and death certificates from local authorities. Subjects lost to follow- up were censored at the date of last contact. Though complete information on occupational history was not collected, any available data on asbestos- related jobs outside the factory were recorded, leading to the identification of 120 (6.1%) subjects with exposure to asbestos previous to the hire in the factory. Therefore, we conducted a sensitivity analysis excluding these subjects. We calculated several time-related exposure variables, including time since first exposure (difference between date of hire and end of follow-up), duration of employment (difference between date of hire and date of last employment), and time since 2624
E. Pira et al.
cessation of exposure (difference between data of last employment and end of follow-up). We computed expected numbers of deaths using the national death rates during 1955-1980 [9], and the regional rates [1, 5] from 1981 onwards. Since national death rates were not available before 1955, the 1955–1959 death rates were applied to period 1946–1954. We computed the SMRs of selected cancers and of total mortality, as the ratio of observed and expected numbers of deaths. The corresponding 95% confidence intervals (CIs) were based on the Poisson distribution of observed deaths [4]. In addition, we fitted Poisson regression models to estimate mortality rate ratios for age at first employment, duration of employment, time since first employment, and time since last employment, after adjustment for sex and age [4]. Age and the exposure variables were introduced in the regression models as time-varying covariates; age was included as continuous variable to limit the number of parameters, and the addition of a term for age2 significantly increased the goodness of it of the models. To assess the presence of linear trends across levels of ordinal variables, we evaluated the Wald chi- square statistic after fitting regression models including a linear term for the covariate of interest.
Results The present analyses include a total of 74,126 person- years of observation (45,769 among women and 28,357 among men). The distribution of subjects and person- years by demographic and exposure characteristics is shown in Table S1. Overall, 920 (46.5%) subjects were alive at the end of the follow-up, 1019 (51.5%) had died and 38 (1.9%) emigrated or were lost to follow-up. Cause of death was unknown for 48 (4.7%) of deceased subjects. Table 1 gives the SMRs in women, men and in both sexes combined. The SMR for all causes was 1.68 (95% CI: 1.57–1.78). Significant excesses mortality were observed for cancers of the peritoneum (SMR 9.1; 95% CI: 21.5– 38.6), lung (SMR 2.96; 95% CI: 2.50–3.49), pleura (SMR 33.7; 95% CI: 25.7–43.4), and ovary (SMR 3.03; 95% CI: 1.69–4.99). The increased mortality was more pronounced in women than men. An increased in mortality from esophageal cancer, based on a small number of deaths, was present in women but not in men. Table 2 gives the observed and expected numbers of deaths from peritoneal, lung, and pleural cancer according to time since last exposure, approximated by time since last employment. For pleural and peritoneal, there was no consistent pattern of SMRs, and no evidence of a decrease, in relation to time since last exposure. For lung cancer, the SMR declined after 25 years since last exposure. We repeated the latter analyses using different categories of time
© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Mortality of Asbestos Textile Workers
E. Pira et al.
Table 1. Observed deaths from selected cancers, and corresponding standardized mortality ratios in a cohort of asbestos textile workers. Italy, 1946-2013. Women
Men
Overall
Cause of death
ICD IX
Obs
SMR (95% CI)
Obs
SMR (95% CI)
Obs
SMR (95% CI)
Oral cavity and pharynx Esophagus Stomach Colorectum Liver Pancreas Peritoneum Larynx Lung Pleura Breast (female) Ovary Prostate Bladder Kidney Brain and central nervous system Lympho-hematopoietic malignancies All cancers All causes of death Person-years
140–149 150 151 152–154, 159.0 155 157 158 161 162 163 174 183 185 188 189 191–192
0 4 5 9 4 1 36 0 42 36 16 15 – 1 3 3
0 (0–3.35) 6.45 (1.76–16.5) 0.99 (0.32–2.32) 0.93 (0.43–1.77) 0.96 (0.26–2.45) 0.23 (0.01–1.27) 41.8 (29.3–57.9) 0 (0–18.4) 5.29 (3.81–7.15) 60.8 (42.6–84.2) 0.86 (0.49–1.40) 3.03 (1.69–4.99) – 1.05 (0.03–5.85) 2.46 (0.51–7.18) 1.20 (0.25–3.50)
9 3 13 24 8 8 12 8 101 24 – – 7 5 1 5
2.03 (0.93–3.86) 0.89 (0.18–2.61) 1.07 (0.57–1.83) 1.73 (1.11–2.58) 1.12 (0.48–2.21) 1.47 (0.63–2.90) 15.3 (7.88–27.0) 1.95 (0.84–3.84) 2.51 (2.04–3.05) 20.2 (13.0–30.1) – – 0.94 (0.38–1.94) 0.87 (0.28–2.03) 0.35 (0.01–1.92) 1.59 (0.51–3.70)
9 7 18 33 12 9 48 8 143 60 16 15 7 6 4 8
1.64 (0.75–3.11) 1.76 (0.70–3.62) 1.05 (0.62–1.66) 1.40 (0.96–1.97) 1.06 (0.55–1.86) 0.92 (0.42–1.74) 29.1 (21.5–38.6) 1.84 (0.79–3.62) 2.96 (2.50–3.49) 33.7 (25.7–43.4) 0.86 (0.49–1.40) 3.03 (1.69–4.99) 0.94 (0.38–1.94) 0.90 (0.33–1.96) 0.97 (0.26–2.49) 1.42 (0.61–2.79)
200–208
7
0.99 (0.40–2.04)
7
0.80 (0.32–1.65)
14
0.89 (0.48–1.49)
140–239 1–999
210 401
2.41 (2.09–2.76) 1.84 (1.66–2.03) 45769
254 618
1.87 (1.65–2.12) 1.58 (1.46–1.72) 28357
464 1019
2.08 (1.90–2.28) 1.68 (1.57–1.78) 74126
Cause of death was unknown for 48 deceased subjects (4.7%). Obs, observed deaths; SMR, standardized mortality ratio; CI, confidence interval.
Table 2. Observed deaths from peritoneal, pleural and lung cancer, and corresponding standardized mortality ratios, according to time since last employment in a cohort of asbestos workers. Italy, 1946–2013. Years since last employment
Open Access
ORIGINAL RESEARCH
Updated mortality study of a cohort of asbestos textile workers Enrico Pira1, Canzio Romano1, Francesco S. Violante2, Andrea Farioli2, Giovanna Spatari3, Carlo La Vecchia4 & Paolo Boffetta5 1Department
of Public Health Sciences and Pediatrics, Turin University, Turin, Italy of Medical and Surgical Sciences (DIMEC), Bologna University, Bologna, Italy 3Department of Environmental Science, Safety, Territory, Food and Health, Messina University, Messina, Italy 4Department of Clinical Sciences and Community Health, Milan University, Milan, Italy 5Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 2Department
Keywords Asbestos, cancer mortality, peritoneal cancer, pleural cancer Correspondence Paolo Boffetta, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York 10029, NY. Tel: +1-212-659-1474; Fax: +1-212-849-2566; E-mail: [email protected] Funding Information This work was supported by internal funds of the participating Institutions. Received: 2 May 2016; Revised: 15 June 2016; Accepted: 21 June 2016
Abstract Limited information is available on risk of peritoneal mesothelioma after asbestos exposure, and in general on the risk of cancer after cessation of asbestos exposure. We updated to 2013 the follow-up of a cohort of 1083 female and 894 male textile workers with heavy asbestos exposure (up to 100 fb/mL), often for short periods. A total of 1019 deaths were observed, corresponding to a standardized mortality ratio (SMR) of 1.68 (95% confidence interval [CI]: 1.57–1.78). SMRs were 29.1 (95% CI: 21.5–38.6) for peritoneal cancer, 2.96 (95% CI: 2.50–3.49) for lung cancer, 33.7 (95% CI: 25.7–43.4) for pleural cancer, and 3.03 (95% CI: 1.69–4.99) for ovarian cancer. For pleural and peritoneal cancer, there was no consistent pattern of risk in relation to time since last exposure, whereas for lung cancer there was an indication of a decline in risk after 25 years since last exposure. The findings of this unique cohort provide novel data for peritoneal cancer, indicating that – as for pleural cancer – the excess risk does not decline up to several decades after cessation of exposure.
Cancer Medicine 2016; 5(9):2623–2628 doi: 10.1002/cam4.824
Introduction The incidence of mesothelioma rises as function of the third or fourth power of time since first asbestos exposure (latency) [12], after taking into account time since cessation of exposure. The other determinants of mesothelioma incidence are average exposure to asbestos (linear relationship), and type of asbestos, with stronger potency of amphiboles than chrysotile [3]. The influence of other time- related aspects such as age at first exposure and duration of exposure appears to be largely or totally explained by latency [12]. These models linking asbestos exposure to mesothelioma incidence have been developed and validated mainly on the basis of results for the pleural form of the disease, since most available cohort studies include a small number of peritoneal mesothelioma [2].
Asbestos is also a cause of lung cancer, and cumulative asbestos exposure appears to be the main determinant of lung cancer incidence, together with the prevalence of tobacco smoking, because of the interaction between the two risk factors [3]. We reported the mortality follow-up to 2004 of a cohort of heavily exposed asbestos textile workers employed between 1946 and 1984, in which we observed 315 cancer deaths compared to 153.9 expected (standardized mortality ratio [SMR] 2.11; 95% confidence interval [CI]: 1.89–2.35), including 39 deaths from peritoneal cancer, 36 deaths from pleural cancer, and 109 deaths from lung cancer [14, 15]. In that analysis there was no difference in the SMR of pleural and peritoneal cancer between workers who had stopped exposure below age 30, and those who had continued exposure after age 40 [15].
© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
2623
Mortality of Asbestos Textile Workers
This cohort is unique since it contains a relatively large number of workers, in particular women, who experienced short-term, high-level exposure to asbestos. As discussed in detail in previous publications [14, 15], various types of asbestos were used in the factory, including crocidolite. Environmental exposure data were available between 1968 and 1977 [14, 17]. Average exposure levels as high as 100 fb/mL were measured in the opening and carding departments in the late 1960s; in the early 1970s average exposure levels were in the range 5–25 fb/mL, and in the late 1970s the average level was 2 fb/mL or less in all departments [14, 17]. The large number of deaths from peritoneal cancer is also an unusual finding. We decided therefore to update the follow- up of this same cohort to 2013, aiming for separate analyses for pleural and peritoneal cancer, as well as lung cancer, with focus on the pattern of mortality following cessation of exposure.
Materials and Methods Detailed information on the cohort is provided in previous reports [14, 15]. In brief, the cohort includes 1083 women and 894 men who had worked in an asbestos textile factory sited in Northern Italy, between 1946 and 1984. The main type of asbestos used in the plant was chrysotile, but crocidolite was also present, although the relative proportion of the two types of fibers over time is not precisely known. The current analysis includes 11 additional subjects as compared to the previous reports, who have been found to fulfill the inclusion criteria. For the present analyses, follow-up was extended to November 2013; subjects were censored when they reached 85 years of age, because of the possibility of misclassification of cause of death in the elderly. Therefore, end of follow-up was defined as date of death, date of last contact, date of 85th birthday, or November 30, 2013, whichever occurred first. We obtained employment data from personnel records at the factory, and ascertained vital status and causes of death through population registers and death certificates from local authorities. Subjects lost to follow- up were censored at the date of last contact. Though complete information on occupational history was not collected, any available data on asbestos- related jobs outside the factory were recorded, leading to the identification of 120 (6.1%) subjects with exposure to asbestos previous to the hire in the factory. Therefore, we conducted a sensitivity analysis excluding these subjects. We calculated several time-related exposure variables, including time since first exposure (difference between date of hire and end of follow-up), duration of employment (difference between date of hire and date of last employment), and time since 2624
E. Pira et al.
cessation of exposure (difference between data of last employment and end of follow-up). We computed expected numbers of deaths using the national death rates during 1955-1980 [9], and the regional rates [1, 5] from 1981 onwards. Since national death rates were not available before 1955, the 1955–1959 death rates were applied to period 1946–1954. We computed the SMRs of selected cancers and of total mortality, as the ratio of observed and expected numbers of deaths. The corresponding 95% confidence intervals (CIs) were based on the Poisson distribution of observed deaths [4]. In addition, we fitted Poisson regression models to estimate mortality rate ratios for age at first employment, duration of employment, time since first employment, and time since last employment, after adjustment for sex and age [4]. Age and the exposure variables were introduced in the regression models as time-varying covariates; age was included as continuous variable to limit the number of parameters, and the addition of a term for age2 significantly increased the goodness of it of the models. To assess the presence of linear trends across levels of ordinal variables, we evaluated the Wald chi- square statistic after fitting regression models including a linear term for the covariate of interest.
Results The present analyses include a total of 74,126 person- years of observation (45,769 among women and 28,357 among men). The distribution of subjects and person- years by demographic and exposure characteristics is shown in Table S1. Overall, 920 (46.5%) subjects were alive at the end of the follow-up, 1019 (51.5%) had died and 38 (1.9%) emigrated or were lost to follow-up. Cause of death was unknown for 48 (4.7%) of deceased subjects. Table 1 gives the SMRs in women, men and in both sexes combined. The SMR for all causes was 1.68 (95% CI: 1.57–1.78). Significant excesses mortality were observed for cancers of the peritoneum (SMR 9.1; 95% CI: 21.5– 38.6), lung (SMR 2.96; 95% CI: 2.50–3.49), pleura (SMR 33.7; 95% CI: 25.7–43.4), and ovary (SMR 3.03; 95% CI: 1.69–4.99). The increased mortality was more pronounced in women than men. An increased in mortality from esophageal cancer, based on a small number of deaths, was present in women but not in men. Table 2 gives the observed and expected numbers of deaths from peritoneal, lung, and pleural cancer according to time since last exposure, approximated by time since last employment. For pleural and peritoneal, there was no consistent pattern of SMRs, and no evidence of a decrease, in relation to time since last exposure. For lung cancer, the SMR declined after 25 years since last exposure. We repeated the latter analyses using different categories of time
© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Mortality of Asbestos Textile Workers
E. Pira et al.
Table 1. Observed deaths from selected cancers, and corresponding standardized mortality ratios in a cohort of asbestos textile workers. Italy, 1946-2013. Women
Men
Overall
Cause of death
ICD IX
Obs
SMR (95% CI)
Obs
SMR (95% CI)
Obs
SMR (95% CI)
Oral cavity and pharynx Esophagus Stomach Colorectum Liver Pancreas Peritoneum Larynx Lung Pleura Breast (female) Ovary Prostate Bladder Kidney Brain and central nervous system Lympho-hematopoietic malignancies All cancers All causes of death Person-years
140–149 150 151 152–154, 159.0 155 157 158 161 162 163 174 183 185 188 189 191–192
0 4 5 9 4 1 36 0 42 36 16 15 – 1 3 3
0 (0–3.35) 6.45 (1.76–16.5) 0.99 (0.32–2.32) 0.93 (0.43–1.77) 0.96 (0.26–2.45) 0.23 (0.01–1.27) 41.8 (29.3–57.9) 0 (0–18.4) 5.29 (3.81–7.15) 60.8 (42.6–84.2) 0.86 (0.49–1.40) 3.03 (1.69–4.99) – 1.05 (0.03–5.85) 2.46 (0.51–7.18) 1.20 (0.25–3.50)
9 3 13 24 8 8 12 8 101 24 – – 7 5 1 5
2.03 (0.93–3.86) 0.89 (0.18–2.61) 1.07 (0.57–1.83) 1.73 (1.11–2.58) 1.12 (0.48–2.21) 1.47 (0.63–2.90) 15.3 (7.88–27.0) 1.95 (0.84–3.84) 2.51 (2.04–3.05) 20.2 (13.0–30.1) – – 0.94 (0.38–1.94) 0.87 (0.28–2.03) 0.35 (0.01–1.92) 1.59 (0.51–3.70)
9 7 18 33 12 9 48 8 143 60 16 15 7 6 4 8
1.64 (0.75–3.11) 1.76 (0.70–3.62) 1.05 (0.62–1.66) 1.40 (0.96–1.97) 1.06 (0.55–1.86) 0.92 (0.42–1.74) 29.1 (21.5–38.6) 1.84 (0.79–3.62) 2.96 (2.50–3.49) 33.7 (25.7–43.4) 0.86 (0.49–1.40) 3.03 (1.69–4.99) 0.94 (0.38–1.94) 0.90 (0.33–1.96) 0.97 (0.26–2.49) 1.42 (0.61–2.79)
200–208
7
0.99 (0.40–2.04)
7
0.80 (0.32–1.65)
14
0.89 (0.48–1.49)
140–239 1–999
210 401
2.41 (2.09–2.76) 1.84 (1.66–2.03) 45769
254 618
1.87 (1.65–2.12) 1.58 (1.46–1.72) 28357
464 1019
2.08 (1.90–2.28) 1.68 (1.57–1.78) 74126
Cause of death was unknown for 48 deceased subjects (4.7%). Obs, observed deaths; SMR, standardized mortality ratio; CI, confidence interval.
Table 2. Observed deaths from peritoneal, pleural and lung cancer, and corresponding standardized mortality ratios, according to time since last employment in a cohort of asbestos workers. Italy, 1946–2013. Years since last employment
