Can lung cancer risk among nickel refinery workers be explained by occupational exposures other than nickel?

Our plain-English summary of Can lung cancer risk among nickel refinery workers be explained by occupational exposures other than nickel?, by T.K. Grimsrud, S.R. Berge, T. Haldorsen, et al (Epidemiology, 2005).

The study

• Authors: T.K. Grimsrud, S.R. Berge, T. Haldorsen, A. Andersen
• Journal: Epidemiology
• Published: 2005;16(2):146-54
• Cited by: 45 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Exposures in nickel refineries represent complex chemical mixtures, but only the effect of nickel has been evaluated quantitatively in epidemiologic studies of nickel workers.

Methods: For a Norwegian refinery, time- and department-specific exposure estimates were developed for arsenic, sulfuric acid mists, and cobalt in air on the basis of personal measurements and chemical data on raw materials and process intermediates. Exposure to asbestos, as well as employment in high-risk occupations outside the refinery, were assessed. We conducted a case-control study nested in a cohort of refinery workers, with 213 cases (diagnosed 1952-1995) and 525 age-matched controls. We analyzed lung cancer risk, adjusted for smoking, by cumulative exposure and duration of work.

Results: There was a substantial association between cumulative exposure to water-soluble nickel and lung cancer risk. Weaker effects were suggested for exposure to arsenic at the refinery and for occupational exposures outside the refinery for 15 years or more. No detectable excess risk was found for refinery exposure to asbestos or sulfuric acid mists, and no dose-related increase in risk was seen from cobalt.

Conclusions: Exposure to water-soluble nickel remained the most likely explanation for the excess lung cancer risk in the cohort. Other occupational exposures did not confound the strong dose-related effect of nickel to any appreciable degree.

In plain English

This study asked whether workplace exposures other than nickel explained high lung cancer rates at a Norwegian nickel refinery. Researchers compared 213 refinery workers with lung cancer diagnosed 1952 to 1995 with 525 workers matched by sex and birth year. All had worked there at least one year. They estimated each worker's exposure to water-soluble nickel, arsenic, sulfuric acid mists and cobalt. They also counted years in departments with likely asbestos exposure (fiber type not stated) and years in cancer-risk outside jobs, and adjusted for smoking. Refinery asbestos exposure had no detectable effect on lung cancer risk. The longest asbestos-exposed group (9.1 to 47 years) had an odds ratio of 0.8 (95% CI 0.3 to 1.7). Arsenic suggested a modest 20 to 30% higher risk with no dose pattern. Fifteen or more years in outside high-risk jobs suggested a 50% excess. Sulfuric acid mists suggested some effect with only smoking adjustment but none after full adjustment; a separate cobalt effect could not be sorted out. The authors concluded water-soluble nickel remained the most likely explanation for the excess lung cancer.

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: Case-control study nested in a cohort of nickel refinery workers, analyzed with multivariable conditional logistic regression and adjusted for smoking
• Who was studied: Workers employed at least one year at a nickel refinery in Norway (cohort employed 1910 to 1994). The study included 213 lung cancer cases diagnosed between December 1952 and August 1995 (94% of those identified) and 525 controls matched by sex and year of birth (94% of the 559 matched controls). Smoking and outside job histories came from interviews with participants or their next of kin.
• Exposure: The refinery exposures studied were water-soluble nickel and any form of nickel, arsenic, sulfuric acid mists and cobalt, each estimated from job-exposure matrices. Asbestos was used to protect workers and equipment against heat. The refinery's medical unit identified the departments and periods with likely non-negligible asbestos exposure, including furnace areas and some maintenance departments and workshops. Asbestos exposure was measured as years in exposed work, and the article does not name a fiber type. The study also counted years in outside occupations judged to carry lung cancer risk: smelter, metallurgy and foundry work; iron and metalware work; painting and paperhanging; and insulators.
• Main results:
  • Asbestos exposure at the refinery had no detectable influence on lung cancer risk. Fully adjusted odds ratios were 1.0 (95% CI 0.6 to 1.7) for low exposure (0.04 to 2.1 years; 31 cases, 71 controls), 0.9 (0.5 to 1.6) for medium exposure (2.2 to 9.0 years; 27 cases, 70 controls) and 0.8 (0.3 to 1.7) for high exposure (9.1 to 47 years; 25 cases, 70 controls). The linear trend was 1.0 per 10 years (0.6 to 1.4).
  • For cumulative exposure to water-soluble nickel, the odds ratio per unit of the log-transformed measure was 1.7 (1.3 to 2.2) when adjusted for smoking only. It was 2.1 (1.3 to 3.2) when adjusted for smoking and all other occupational exposures. The nickel estimates changed only slightly with these adjustments.
  • Arsenic exposure at the refinery suggested a modest 20 to 30% elevated lung cancer risk, with no dose-dependent increase. Adjusted odds ratios were 1.3 (0.7 to 2.3) for low, 1.2 (0.7 to 2.3) for medium and 1.2 (0.6 to 2.4) for high exposure.
  • Work in carcinogenic-risk occupations outside the refinery suggested a positive trend. The adjusted odds ratio was 1.5 (0.8 to 2.8) for 14.5 to 49 years of such work (26 cases, 60 controls).
  • Some effect of arsenic, sulfuric acid mists and cobalt was suggested when each was examined separately with adjustment for smoking. These exposures were positively correlated with water-soluble nickel, and the effects largely disappeared in the full model.
  • Sulfuric acid mists showed no effect in the fully adjusted model.
  • A separate effect of cobalt could not be identified. The reasons were collinearity and the fact that everyone exposed to nickel was also exposed to cobalt.
  • By length of work in refinery department groups, 12 to 48 years in electrolysis, leaching and associated (hydrometallurgical) departments gave an odds ratio of 5.1 (2.9 to 9.1), based on 62 cases and 80 controls.
• The authors' conclusion: The authors concluded that exposures other than nickel did not explain the large excess of lung cancer among these Norwegian nickel refinery workers, and that water-soluble nickel salts remained the strongest candidate. On asbestos, they cited a separate study of the same cohort that found pleural plaques. They suggested that asbestos exposure at the plant, though sufficient to produce pleural plaques, was presumably too low to produce excess cancer.
• Limitations the authors state:
  • Apart from cobalt and sulfuric acid mists in recent periods, there were no air measurements for exposures other than nickel, so the estimated levels probably contain errors.
  • Adequate nickel measurements existed only for the last quarter century, although important exposures occurred during the preceding 60 years.
  • Occupational histories came from interviews, and controls tend to live longer than lung cancer patients, so the data may be affected by information or recall bias.
  • Few workers were exposed to sulfuric acid mists (14% of controls), giving roughly a 50% chance of detecting a relative risk of 2.
  • A possible effect of cobalt could not be distinguished from the effect earlier attributed to insoluble forms of nickel.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Occupational Exposure, Case-Control Study, Cumulative Exposure.

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