Retrospective mortality cohort study of Italian workers compensated for silicosis

A Marinaccio; A Scarselli; G Gorini; E Chellini; M Mastrantonio; R Uccelli; P Altavista; R Pirastu; D F Merlo; M Nesti

doi:10.1136/oem.2006.027854

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Retrospective mortality cohort study of Italian workers compensated for silicosis

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Authors' Reply to Erren et al.
Alessandro Marinaccio
Published on: 27 April 2016
Mortality results in workers compensated for silicosis in Italy - Facts and possible artefacts
Thomas C. Erren
Published on: 27 April 2016

Published on: 27 April 2016

Authors' Reply to Erren et al.

Alessandro Marinaccio, Researcher
Other Contributors:
- Alberto Scarselli, Giuseppe Gorini, Elisabetta Chellini, Marina Mastrantonio, Raffaella Uccelli, Pierluigi Altavista, Franco Merlo and Massimo Nesti

Mortality results in workers compensated for silicosis in Italy by job and disability degree.

We wish to thank our German colleagues for giving us the opportunity to clear some points of the mortality study of workers compensated for silicosis in Italy [1]. The large number of silicotic compensated workers investigated allowed us to perform specific analyses to reduce cohort heterogeneity. Subcohort has been investigated according to the year of compensation assignment, to the level of disability (more or less than 31% disability) and to the job. Among the overall cohort an increased mortality from lung cancer in males has been observed as reported (SMR 1.10, 95% CI 1.03-1.18). In the subcohort of workers with a disability degree more than 31% (2,717 subjects) cause specific SMRs are generally higher (see table 1), e.g. for trachea, bronchus and lung cancer (SMR 1.16, 95% CI 0.99-1.35), esophagus cancer (SMR 1.39, 95% CI 0.83-2.32), larynx cancer (SMR 1.77, 95% CI 1.17-2.68) and respiratory system cancer (SMR 1.19, 95% CI 1.03-1.38). In the group of compensated subjects with a disability degree more than 31% who worked in quarries/mines, SMR for trachea, bronchus and lung cancer is 1.39 (95 % CI 0.96-2.01) and in the group of compensated subjects who worked in glass industry is 1.17 (95 % CI 0.94-1.47) (not reported in table). This last finding is consistent with recent evidence from a previous study of art glass workers conducted in Tuscany [2]. The analyses of these selected cohort, not presented in the original article, strengthen, in our opinion, the internal consistency and specificity of the observed increase for lung cancer among silicotics. As far as the Healthy Worker Effect (HWE) is concerned, we are fully aware of the complexity of the phenomenon which can be seen either as an example of confounding or selection bias in occupational studies. In a cohort of workers selected on the basis of compensation additional and peculiar factors could be in place [3-4]. We assess an expected pattern of disease in our study, with a significant increase for silica - associated causes (lung cancer, silicosis and other pneumoconiosis): on this basis the role of selection bias can be regarded as minor, if present [5].

Table 1. Selected cause specific mortality among male workers compensated for silicosis, Tuscany, Italy, between 1946 and 1979; standardised mortality ratios (SMRs), 95% confidence interval (95% CI) in the total cohort and in the selecetd cohort of male workers with more than 31% of disability degree.

Selected cause specific mortality	Overall cohort (N = 14090)		Selected cohort of male workers with more than 31% of disability degree (N = 2799)
	SMR	95% CI	SMR	95% CI
All causes	0,93	0,91-0,95	1,02	0,97-1,07
Infectious diseases	1,79	1,43-2,25	2,91	1,95-4,37
Tuberculosis	2,91	2,21-3,82	5,18	3,26-8,22
All cancers	0,94	0,91-0,98	0,99	0,91-1,08
Lip oral cavity and pharynx	0,14	0,06-0,29	0,36	0,13-1,00
Digestive organs and peritoneum	0,91	0,85-0,97	0,93	0,80-1,07
Esophagus	1,01	0,78-1,32	1,39	0,83-2,32
Stomach	0,83	0,74-0,92	0,97	0,77-1,23
Colorectal	0,84	0,74-0,96	0,87	0,64-1,17
Liver	2,17	1,86-2,54	1,75	1,18-2,60
Gallbladder and extrahepatic bile ducts	0,81	0,53-1,22	0,64	0,23-1,79
Pancreatic	0,97	0,80-1,19	0,93	0,58-1,47
Peritoneum	0,37	0,15-0,91	0,00	0,00-0,00
Respiratory tract	1,09	1,02-1,16	1,19	1,03-1,38
Nose	1,06	0,31-3,67	0,00	0,00-0,00
Larynx	0,89	0,69-1,15	1,77	1,17-2,68
Trachea, bronchus and lungs	1,11	1,04-1,19	1,16	0,99-1,35
Respiratory system diseases	2,50	2,39-2,62	3,11	2,83-3,41
Chronic obstructive pulmonary disease	0,79	0,71-0,88	0,95	0,76-1,19
Bronchitis	0,84	0,75-0,94	0,97	0,76-1,23
Asthma	0,49	0,30-0,80	1,10	0,52-2,31
Anthracosilicosis	25,53	7,36-88,57	67,16	12,70-355,17
Asbestosis	8,62	2,49-29,91	46,32	13,43-159,76
Silicosis	21,82	20,67-23,04	26,78	23,95-29,94
Other pneumoconiosis	19,79	14,43-27,13	26,82	14,54-49,46

References

[1] Marinaccio A, Scarselli A, Gorini G, Chellini E, Mastrantonio M, Uccelli R, Altavista P, Pirastu R, Merlo DF, Nesti M.Retrospective mortality cohort study of Italian workers compensated for silicosis. Occup Environ Med Nov;63(11):762-5

[2] Pirastu R, Bartoli D, Battista G, De Santis M, Iaia TE, Orsi D, Tarchi M, Valiani M. A cohort mortality study of art glass workers in Tuscany, Italy. Scandinavian Journal of Work Environment & Health 1998;24 (5):1-6

[3] Checkoway H, Pearce N, Kriebel D. Research Methods in Occupational Epidemiology 2nd edition. Oxford, Oxford University Press, 2004

[4] Carpenter LM. Editorial. Some observations on the healthy worker effect. British Journal of Industrial Medicine 1987; 44: 289-291

[5] Savitz DA. Interpreting Epidemiologic Evidence-Strategies for study design and analysis. Oxford, Oxford University Press, 2003

Alessandro Marinaccio (1), Alberto Scarselli (1), Giuseppe Gorini (2), Elisabetta Chellini (2), Marina Mastrantonio (3), Raffaella Uccelli (3), Pierluigi Altavista (3), Roberta Pirastu (4) , Domenico Franco Merlo (5) and Massimo Nesti (1) .

1 ISPESL - Italian Institute for Occupational Safety and Prevention, Epidemiology Unit, Department of Occupational Medicine, Rome, Italy

2 CSPO - Center for Study and Prevention of Cancer, – Scientific Institute of Tuscany – Tuscan Cancer Institute, Unit of Occupational and Environmental Epidemiology, Florence, Italy

3 ENEA - Italian Agency for New Technologies, Energy and the Environment, Unit of Toxicology and Environmental Sciences, Rome, Italy

4 University of Rome "La Sapienza", Department of Animal and Human Biology, Rome Italy

5 IST - Italian Cancer Research Institute, Environmental Epidemiology and Applied Biostatistics, Genoa, Italy

Corresponding author: Alessandro Marinaccio, ISPESL (Italian institute for occupational safety and prevention) – Department of Occupational Medicine – Epidemiology Unit Via Alessandria 220/E; 00198 Rome – Italy , Tel.: +39-06-44280396; fax +39 -06-44250639 E-mail address: alessandro.marinaccio@ispesl.it

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Conflict of Interest:
None declared.

Published on: 27 April 2016
Mortality results in workers compensated for silicosis in Italy - Facts and possible artefacts
- Thomas C. Erren, MD MPH
- Other Contributors:
  Peter Morfeld, Christine B. Glende, Claus Piekarski
Mortality results in a large cohort of workers compensated for silicosis in Italy – Facts and possible artefacts
With interest we read the article by Marinaccio et al. [1]. Their retrospective mortality study of some 14.000 men compensated for silicosis in the Tuscany region would constitute a powerful addition to studies of cancer risks in compensated silicotics worldwide. In particular, some study results could c...
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Mortality results in a large cohort of workers compensated for silicosis in Italy – Facts and possible artefacts
With interest we read the article by Marinaccio et al. [1]. Their retrospective mortality study of some 14.000 men compensated for silicosis in the Tuscany region would constitute a powerful addition to studies of cancer risks in compensated silicotics worldwide. In particular, some study results could contribute to discussions as to under what circumstances crystalline silica, classified as Group 1 carcinogen since 1997 [2], acts as a lung carcinogen. Indeed, with cancers of the ‘trachea, bronchus and lungs’ observed/estimated in approximately 800 males, this study alone considered almost three times as many lung cancer deaths as the seven other SMR studies in compensated silicotics together which were included in a meta-analysis [3] which Marinaccio and colleagues cited. And yet, before weighting the possible impact of the published information, we would kindly like to ask for clarification of uncertainties around some results. Examples include that (i) this study’s estimate of mortality for lung cancer [SMR=1.10;95%CI=1.03-1.18] is discrepantly different from the individual and combined estimates of the aforementioned previous SMR studies [summary relative risk=2.40;95%CI=2.12-2.71], (ii) this study would point to a significant decrease of overall mortality below 1, (iii) in view of some 30 SMRs for cancers and other diseases which are partly considerably below the 1, these study results need further discussion. In our view, the invocation of the Healthy Worker Effect without additional qualification does not suffice to interpret the findings in this heterogeneous cohort. Conceivably, details of silicosis compensation in the Tuscany region – but this had to be very different in practice and effect from other regions in Italy [4-5] – may have led to significant selection biases. In any case, we disagree with what the authors state in their discussion: their finding of a marginally elevated excess mortality for lung cancer among silicotics is not consistent with the results of previous studies but it is discrepant and needs to be explained – in detail and in context.
References
[1] Marinaccio A, Scarselli A, Gorini G, Chellini E, Mastrantonio M, Uccelli R, Altavista P, Pirastu R, Merlo DF, Nesti M. Retrospective mortality cohort study of Italian workers compensated for silicosis. Occup Environ Med 2006 [Epub ahead of print].
[2] International Agency for Research on Cancer. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Vol. 68. Silica, Some Silicates, Coal Dust and para-Aramid Fibrils. Lyon: International Agency for Research on Cancer, 1997.
[3] Smith AH, Lopipero PA, Barroga VR. Meta-analysis of studies of lung cancer among silicotics. Epidemiology 1995;6:617-624.
[4] Puntoni R, Goldsmith DF, Valerio F, Vercelli M, Bonassi S, Di Giorgio F, Ceppi M, Stagnaro E, Filiberti R, Santi L, Merlo F. A cohort study of workers employed in a refractory brick plant. Tumori 1988;74:27-33.
[5] Zambon P, Simonato L, Mastrangelo G, Winkelmann R, Saia B, Crepet M. A mortality study of workers compensated for silicosis during 1959 to 1963 in the Veneto region of Italy. In: Goldsmith DF, Winn DM, Shy CM, eds. Silica, Silicosis and Cancer: Controversy in Occupational Medicine. New York: Praeger, 1986;367-374.
Thomas C. Erren, Peter Morfeld, Christine B. Glende, Claus Piekarski
Institute and Policlinic for Occupational and Social Medicine, School of Medicine and Dentistry, University of Cologne, Germany
Corresponding author: Thomas C. Erren MD, MPH Institute and Policlinic for Occupational and Social Medicine School of Medicine and Dentistry University of Cologne, Germany Tel.: +49-221-4785819; fax: +49-221-4785119 E-mail address: tim.erren@uni-koeln.de
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Conflict of Interest:
None declared.
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