Cohort study of workers employed in an Italian tire manufacturing plant, 1962-2004

Our plain-English summary of Cohort study of workers employed in an Italian tire manufacturing plant, 1962-2004, by D. Mirabelli, A.M. Cacciatore, D. Ferrante, et al (Cancer Causes & Control, 2012).

The study

• Authors: D. Mirabelli, A.M. Cacciatore, D. Ferrante, P. Amendola, R. Vermeulen, F. Merletti
• Journal: Cancer Causes & Control
• Published: 2012;23(12):2023-9
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To investigate mortality and bladder cancer incidence among workers of a tire manufacturing plant where antioxidants severely contaminated by beta-naphthylamine were never used.

Methods: Mortality follow-up was performed of 9,501 workers first hired between 1962 when the plant started operations and 2000. Person-years of observation from 1962 to 2004, expected deaths, and standardized mortality ratios (SMR) were calculated. Follow-up for bladder cancer incidence from 1988 to 2003 was carried out, and standardized incidence ratios (SIR) were calculated. Multivariable (Poisson) analyses of bladder cancer incidence and mortality by duration of employment (DOE) and time since first employment (TSFE) were performed.

Results: Among men, SMRs were significantly reduced for all causes, all cancers, lung cancer, cardiovascular, and ischemic heart diseases. Bladder cancer mortality and leukemia mortality were close to expectation but increased with TSFE. Seventy-two incident cases of bladder cancer were observed (SIR = 1.15; 95 % confidence interval 0.90-1.44), and multivariable analysis suggested a possible increase in rate ratios with DOE. Among women, mortality was close to expectation, but the limited number of observed deaths prevented detailed analyses.

Conclusions: No significant cancer excess was observed. A suggestion of increased risks of bladder cancer and leukemias after extended TSFE was present in men, deserving consideration as exposure to carcinogens possibly occurred early in plant operation. Furthermore, this cohort of workers is still relatively young and less than 10 % have died. There was, thus, limited power to detect small increases in risk at rare cancer sites. Further epidemiological surveillance of this cohort is planned.

In plain English

This study followed 9,501 workers (8,686 men, 815 women) hired 1962 to 2000 at a tire plant in Cuneo, Italy, for deaths through 2004 and bladder cancer diagnoses from 1988 to 2003. Its focus was rubber-industry chemicals, not asbestos; exposure measurements and job histories were unavailable. Among men, deaths from all causes, all cancers and lung cancer were significantly lower than expected from regional rates. Bladder cancer (10 deaths; SMR 0.95; 95% CI 0.46–1.75) and leukemia (13 deaths; SMR 1.24; 95% CI 0.66–2.11) mortality was close to expectation, though both tended to rise with time since first employment. Men had 72 new bladder cancers, not significantly more than expected (SIR 1.15; 95% CI 0.90–1.44). All six pleural cancer or mesothelioma deaths were confirmed as malignant mesotheliomas (SMR 1.52; 95% CI 0.56–3.30). The authors checked these six workers for exposure to talc contaminated by asbestiform fibers and to insulating materials, finding no evidence of either. The authors concluded no significant cancer excess was linked to workplace carcinogens. They noted the cohort was young and fewer than 10% had died.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cohort study of mortality (standardized mortality ratios against Piedmont regional rates), with a follow-up of bladder cancer incidence (standardized incidence ratios against Turin rates)
• Who was studied: 9,501 workers (8,686 men and 815 women) hired between 1962 and May 2000 at a tire manufacturing plant in Cuneo, Piedmont, Italy, followed to 31 December 2004 at the latest
• Exposure: Employment in tire manufacturing. The main antioxidant from 1962 to 1984 was phenyl-beta-naphthylamine, later replaced by para-phenylenediamine derivatives; aromatic extender oils were also used. Duration of employment was the only exposure index available. Asbestos was not measured.
• Main results:
  • Men: all-cause mortality was significantly lower than expected (SMR = 0.93; 95% CI 0.86–0.99), based on 859 deaths
  • Men: mortality from all cancers was significantly lower than expected (SMR = 0.81; 95% CI 0.72–0.91)
  • Men: lung cancer mortality was significantly lower than expected, with 83 deaths (SMR 0.74; 95% CI 0.59–0.92)
  • Men: six deaths had pleural cancer or mesothelioma as the cause, all confirmed by the Piedmont Registry of Malignant Mesotheliomas (SMR = 1.52; 95% CI 0.56–3.30)
  • In the six mesothelioma cases, the authors investigated possible exposure to talc contaminated by asbestiform fibers, used as an anti-tack agent, and to insulating materials, and found no evidence of either exposure
  • Men: bladder cancer mortality (10 deaths; SMR = 0.95; 95% CI 0.46–1.75) and leukemia mortality (13 deaths; SMR = 1.24; 95% CI 0.66–2.11) were close to expectation
  • Men: bladder cancer and leukemia SMRs tended to increase with time since first employment, but the trend test was not significant
  • Men: in multivariable analysis, bladder cancer mortality showed an increasing trend with time since first employment (p less than 0.02)
  • Men: 72 incident bladder cancers arose from 1988 onward; incidence was not significantly different from expected (SIR = 1.15; 95% CI 0.90–1.44)
  • Men: bladder cancer incidence rate ratios increased with duration of employment, but no single estimate and no trend test was statistically significant
  • Men: nasal cavity cancer mortality was increased (3 deaths; SMR 4.93; 95% CI 1.02–14.40)
• The authors' conclusion: The authors concluded that a healthy worker effect was present and that no significant cancer excess could be linked to workplace carcinogens. Any suggestion of increased bladder cancer and leukemia risk was limited to exposures that may have occurred in the distant past.
• Limitations the authors state:
  • There were no historical exposure measurements and no individual job histories
  • A healthy worker effect biased the comparison with the general population
  • Identification of incident bladder cancers may have been incomplete
  • Using Turin as the reference population may have overestimated expected bladder cancer cases, which would make the SIR too low
  • Analyzing the whole cohort together may have diluted an effect confined to one exposure group
  • The cohort was young with few deaths, limiting power to detect small increases in rare cancers
  • Rate ratios had wide confidence intervals because few deaths were observed
  • Detailed analyses were restricted to men because there were few deaths among women

Topics

Medical terms in this study, explained in our Lexicon: Cohort Study, standardized mortality ratio (SMR), Standardized Incidence Ratio (SIR), Lung Cancer, confidence interval, rate ratio.

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• Asbestos-related disease in employees of a steel mill and a glass bottle manufacturing plant — R.S. Kronenberg, J.L. Levin, et al. (1991)
• Work environment of plants manufacturing asbestos-containing products in Japan — T. Higashi, H. Hori, et al. (1994)
• Mortality among shipbreaking workers in Taiwan--a retrospective cohort study from 1985 to 2008 — W.T. Wu, Y.H. Lu, et al. (2013)
• Cancer mortality in a northern Italian cohort of rubber workers — A. Fischbein (1990)

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