Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY)

Our plain-English summary of Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY), by A. Olsson, L. Bouaoun, J. Schüz, et al (Environmental Health Perspectives, 2024).

The study

• Authors: A. Olsson, L. Bouaoun, J. Schüz, R. Vermeulen, T. Behrens, C. Ge, H. Kromhout, J. Siemiatycki, P. Gustavsson, P. Boffetta, B. Kendzia, L. Radoi, C. Barul, S. Karrasch, H.E. Wichmann, D. Consonni, M.T. Landi, N.E. Caporaso, F. Merletti, E. Migliore, L. Richiardi, K.H. Jöckel, W. Ahrens, H. Pohlabeln, G. Fernández-Tardón, D. Zaridze, J.K. Field, J. Lissowska, B. Świątkowska, J.R. McLaughlin, P.A. Demers, M. Schejbalova, L. Foretova, V. Janout, T. Pándics, E. Fabianova, D. Mates, F. Forastiere, K. Straif, T. Brüning, J. Vlaanderen, S. Peters
• Journal: Environmental Health Perspectives
• Published: 2024;132(1):17005
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents.

Objectives: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking.

Methods: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI).

Results: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8).

Discussion: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

In plain English

This pooled analysis (the SYNERGY project) combined 14 lung cancer case-control studies from Europe and Canada, conducted 1985 to 2010: 16,901 cases and 20,965 controls. A job-exposure matrix estimated whether each person had ever been exposed at work to asbestos (fiber type not named), respirable crystalline silica, nickel, hexavalent chromium (chromium-VI) or polycyclic aromatic hydrocarbons (PAH). The authors analysed pairs of exposures, adjusting for smoking. About 40% of male and 11% of female controls had asbestos exposure. Among men, every pair examined was associated with increased lung cancer risk; chromium-VI with nickel was not analysed because those exposures were highly correlated. However, asbestos with chromium-VI and asbestos with nickel showed statistically significantly smaller-than-expected combined effects for squamous cell cancer and/or lung cancer overall. Among women, asbestos plus silica had an odds ratio of 4.32 (95% CI 1.35 to 7.29) for small cell lung cancer, a more than multiplicative effect; estimates for women were imprecise. The authors concluded that combined effects deviated little or not at all from additive or multiplicative patterns, but co-exposure generally carried higher risk than single exposures.

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: Pooled analysis of 14 population- or hospital-based lung cancer case-control studies (SYNERGY project), analysed with logistic regression and tests of interaction on additive and multiplicative scales
• Who was studied: 16,901 lung cancer cases and 20,965 control subjects from studies in Europe and Canada conducted between 1985 and 2010 (13,605 male cases and 16,451 male controls; 3,296 female cases and 4,514 female controls)
• Exposure: Ever vs. never occupational exposure to asbestos (fiber type not specified), respirable crystalline silica, chromium-VI, nickel and PAH, assigned to lifetime job histories with a quantitative job-exposure matrix (SYN-JEM). Exposures were analysed in pairs. The chromium-VI/nickel pair was not investigated because the two exposures were highly correlated.
• Main results:
  • About 40% of male controls and 11% of female controls were estimated to have had asbestos exposure in at least one job
  • Among men, all pairs investigated were associated with increased lung cancer risk compared with men never exposed to either agent in the pair. The chromium-VI/nickel pair was not investigated.
  • Among men, asbestos/chromium-VI, asbestos/nickel, chromium-VI/PAH and nickel/PAH showed statistically significant negative departures (combined effects smaller than expected) on both additive and multiplicative scales, for squamous cell cancer and/or lung cancer overall
  • Among men, chromium-VI/silica was slightly more than additive for adenocarcinoma (RERI 0.24; 95% CI 0.02 to 0.46; p = 0.05)
  • Among women, for small cell lung cancer, asbestos/silica (OR 4.32; 95% CI 1.35 to 7.29; p = 0.02) and chromium-VI/silica (OR 5.80; 95% CI 1.10 to 10.51; p = 0.05) showed more than multiplicative effects
  • Among women, PAH/silica showed a more than additive effect for small cell lung cancer (RERI 3.45; 95% CI 0.10 to 6.8; p = 0.01)
  • Among men stratified by smoking status, asbestos/chromium-VI was submultiplicative in former smokers (p = 0.04) and current smokers (p = 0.02), and asbestos/nickel was submultiplicative in former smokers (p = 0.02). Departure from additivity was not statistically significant for these.
• The authors' conclusion: The authors concluded that there was small or no deviation from additive or multiplicative effects, but that co-exposure to the selected lung carcinogens generally resulted in higher risk than exposure to individual agents
• Limitations the authors state:
  • Relatively low participation in a few studies may have caused selection bias
  • Possible incorrect recall of past jobs and smoking habits
  • The job-exposure matrix ignores differences in exposure between workers in the same job
  • Nickel and chromium-VI exposures were highly correlated, so their effects cannot be separated with certainty
  • The analysis did not consider whether the two exposures occurred in the same job or in different jobs
  • Only ever vs. never exposure was used, not cumulative exposure levels or other exposure measures
  • Exposures to more than two of the agents were not analysed
  • Estimates were less precise (wider confidence intervals) among never smokers and among women

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, Meta-Analysis, Crystalline, Histological Subtype, Odds Ratio, confidence interval, Habit.

Related studies

• Lung cancer risk among bricklayers in a pooled analysis of case-control studies — D. Consonni, S. De Matteis, et al. (2015)
• Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies — A.C. Olsson, R. Vermeulen, et al. (2017)
• Parental occupational exposure and risk of childhood central nervous system tumors: a pooled analysis of case-control studies from Germany, France, and the UK — C. Huoi, A. Olsson, et al. (2014)
• Development of an exposure measurement database on five lung carcinogens (ExpoSYN) for quantitative retrospective occupational exposure assessment — S. Peters, R. Vermeulen, et al. (2012)
• SYN-JEM: A Quantitative Job-Exposure Matrix for Five Lung Carcinogens — S. Peters, R. Vermeulen, et al. (2016)
• Occupational lung cancer risk for men in Germany: results from a pooled case-control study — I. Brüske-Hohlfeld, M. Möhner, et al. (2000)

Browse more research in Environmental Health Perspectives, or return to medical research.