SYNERGY - Pooled analysis of case-control studies

to investigate the interaction of selected occupational carcinogens in the development of lung cancer

Summary appraisal of the achieved results

The primary focus of "SYNERGY" was to investigate the interaction of selected occupational carcinogens and tobacco smoke in the development of lung cancer. For this purpose, international population-based case-control studies were combined into one pooled data set (including approx. 18,000 lung cancer cases and 22,000 control subjects).

To estimate each participant’s life-long cumulative exposure to the selected carcinogens, a total of 100,000 personal measurements from secondary measurement databases were integrated into a job-exposure-matrix using an innovative approach. Description of dose-effect relationships and combined effects was based on the odds ratio as the relevant relative risk measure in case-control studies.

Agent-related analyses in SYNERGY so far have focused on dose-response relationships with respect to occupational exposure to asbestos. Because population-based studies include a large number of occupational activities and typical high-risk occupations are usually not included, these studies primarily produce evidence for the low-dose range of exposures, for which only a few studies with reliable risk estimates are available so far. In SYNERGY, the lung cancer risk in men exposed to 0.5 fibre-years was increased about 1.25-times compared to unexposed male subjects.

Due to the comprehensive number of cases in SYNERGY, we were able to determine the combined effect of an exposure to asbestos and smoking. We showed an over-additive effect, a result that has not yet been described in the literature in a comparably large data set. The analyses of dose-response relationships for the other carcinogenic hazardous substances in SYNERGY are still being pursued.

In addition to agent-related risks, SYNERGY also analysed lung cancer risks for selected risk occupations. Increased risks were observed for welders, miners, bricklayers and hairdressers. In addition, the risk of lung cancer was increased for occupational exposure to organic dust, diesel engine emissions and low occupational social status.

In summary, SYNERGY has developed into an important platform for occupational epidemiological lung cancer research, addressing a variety of important questions including agent-related lung cancer risks in the low-dose range and risks in relevant subgroups such as women and non-smokers.

One of SYNERGY's limitations is that the used measurement values were from from secondary measurement databases and therefore not collected directly from the study participants. Thus, these measurements do not necessarily correlate with the study participants' work history with respect to location, time period, and content. This uncertainty leads to a certain degree of exposure misclassification, which may lead to biased risk estimations.

Overall, it can be stated that the epidemiological exposure and risk estimation using secondary measurement data for predominantly non-highly exposed occupations is limited due to the complexity of the exposure conditions. This complexity prevented further analyses of combined effects between the five model carcinogens in SYNERGY so far. Therefore, insights gained from SYNERGY should focus primarily on aspects of occupational prevention. Especially, questions of syncarcinogenesis derived from SYNERGY should primarily not be used in compensation law suits for occupational diseases. 

SYNERGY – Summary Appraisal of the Achieved Results (PDF, 106 kB, non-accessible)

References

  1. Behrens T, Kendzia B, Treppmann T, Olsson A, Jöckel KH, Gustavsson P, Pohlabeln H, Ahrens W, Brüske I, Wichmann HE, Merletti F, Mirabelli D, Richiardi L, Simonato L, Zaridze D, Szeszenia-Dabrowska N, Rudnai P, Lissowska J, Fabianova E, Tardón A, Field J, Stanescu Dumitru R, Bencko V, Foretova L, Janout V, Siemiatycki J, Parent ME, McLaughlin J, Demers P, Landi MT, Caporaso N, Kromhout H, Vermeulen R, Peters S, Benhamou S, Stücker I, Guida F, Consonni D, Bueno-de-Mesquita B, 't Mannetje A, Pearce N, Tse LA, Yu IT, Plato N, Boffetta P, Straif K, Schüz J, Pesch B, Brüning T. Lung cancer risk among bakers, pastry cooks and confectionary makers: the SYNERGY study. Occup Environ Med 2013;70(11):810-4
  2. Behrens T, Groß I, Siemiatycki J, Conway DI, Olsson A, Stücker I, Guida F, Jöckel KH, Pohlabeln H, Ahrens W, Brüske I, Wichmann HE, Gustavsson P, Consonni D, Merletti F, Richiardi L, Simonato L, Fortes C, Parent ME, McLaughlin J, Demers P, Landi MT, Caporaso N, Zaridze D, Szeszenia-Dabrowska N, Rudnai P, Lissowska J, Fabianova E, Tardón A, Field JK, Dumitru RS, Bencko V, Foretova L, Janout V, Kromhout H, Vermeulen R, Boffetta P, Straif K, Schüz J, Hovanec J, Kendzia B, Pesch B, Brüning T. Occupational prestige, social mobility and the association with lung cancer in men. BMC Cancer 2016;16:395.
  3. Behrens T, Taeger D, Pallapies D, Brüning T. Zur Diskussion gestellt: Synergistische Effekte nach Mehrfachexposition –Bewertung für die Regulation. Arbeitsmed Sozialmed Umweltmed 2018a; 53: 452–458
  4. Behrens T, Pesch B, Brüning T. Zur Diskussion gestellt: Herausforderungen bei der Bewertung synergistischer Effekte aus bevölkerungsbezogenen Studien. Arbeitsmed Sozialmed Umweltmed 2018b; 53: 526-529
  5. Bigert C, Gustavsson P, Straif K, Pesch B, Brüning T, Kendzia B, Schüz J, Stücker I, Guida F, Brüske I, Wichmann HE, Pesatori AC, Landi MT, Caporaso N, Tse LA, Yu IT, Siemiatycki J, Pintos J, Merletti F, Mirabelli D, Simonato L, Jöckel KH, Ahrens W, Pohlabeln H, Tardón A, Zaridze D, Field J, 't Mannetje A, Pearce N, McLaughlin J, Demers P, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Dumitru RS, Bencko V, Foretova L, Janout V, Boffetta P, Forastiere F, Bueno-de-Mesquita B, Peters S, Vermeulen R, Kromhout H, Olsson AC. Lung cancer risk among cooks when accounting for tobacco smoking: a pooled analysis of case-control studies from Europe, Canada, New Zealand, and China. J Occup Environ Med 2015;57(2):202-9.
  6. Bigert C, Gustavsson P, Straif K, Taeger D, Pesch B, Kendzia B, Schüz J, Stücker I, Guida F, Brüske I, Wichmann HE, Pesatori AC, Landi MT, Caporaso N, Tse LA, Yu IT, Siemiatycki J, Lavoué J, Richiardi L, Mirabelli D, Simonato L, Jöckel KH, Ahrens W, Pohlabeln H, Tardón A, Zaridze D, Field JK, 't Mannetje A, Pearce N, McLaughlin J, Demers P, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Stanescu Dumitru R, Bencko V, Foretova L, Janout V, Boffetta P, Peters S, Vermeulen R, Kromhout H, Brüning T, Olsson AC. Lung Cancer Among Firefighters: Smoking-Adjusted Risk Estimates in a Pooled Analysis of Case-Control Studies. J Occup Environ Med 2016;58(11):1137-1143.
  7. Consonni D, De Matteis S, Pesatori AC, Bertazzi PA, Olsson AC, Kromhout H, Peters S, Vermeulen RC, Pesch B, Brüning T, Kendzia B, Behrens T, Stücker I, Guida F, Wichmann HE, Brüske I, Landi MT, Caporaso NE, Gustavsson P, Plato N, Tse LA, Yu IT, Jöckel KH, Ahrens W, Pohlabeln H, Merletti F, Richiardi L, Simonato L, Forastiere F, Siemiatycki J, Parent MÉ, Tardón A, Boffetta P, Zaridze D, Chen Y, Field JK, 't Mannetje A, Pearce N, McLaughlin J, Demers P, Lissowska J, Szeszenia-Dabrowska N, Bencko V, Foretova L, Janout V, Rudnai P, Fabiánová E, Stanescu Dumitru R, Bueno-de-Mesquita HB, Schüz J, Straif K. Lung cancer risk among bricklayers in a pooled analysis of case-control studies. Int J Cancer 2015;136(2):360-71.
  8. Denholm R, Schüz J, Straif K, Stücker I, Jöckel KH, Brenner DR, De Matteis S, Boffetta P, Guida F, Brüske I, Wichmann HE, Landi MT, Caporaso N, Siemiatycki J, Ahrens W, Pohlabeln H, Zaridze D, Field JK, McLaughlin J, Demers P, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Dumitru RS, Bencko V, Foretova L, Janout V, Kendzia B, Peters S, Behrens T, Vermeulen R, Brüning T, Kromhout H, C Olsson A. Is previous respiratory disease a risk factor for lung cancer? Am J Respir Crit Care Med 2014;190(5):549-59.
  9. Hovanec J, Siemiatycki J, Conway DI, Olsson A, Stücker I, Guida F, Jöckel KH, Pohlabeln H, Ahrens W, Brüske I, Wichmann HE, Gustavsson P, Consonni D, Merletti F, Richiardi L, Simonato L, Fortes C, Parent ME, McLaughlin J, Demers P, Landi MT, Caporaso N, Tardón A, Zaridze D, Szeszenia-Dabrowska N, Rudnai P, Lissowska J, Fabianova E, Field J, Dumitru RS, Bencko V, Foretova L, Janout V, Kromhout H, Vermeulen R, Boffetta P, Straif K, Schüz J, Kendzia B, Pesch B, Brüning T, Behrens T. Lung cancer and socioeconomic status in a pooled analysis of case-control studies. PLoS One 2018;13(2):e0192999.
  10. Kendzia B, Behrens T, Jöckel KH, Siemiatycki J, Kromhout H, Vermeulen R, Peters S, Van Gelder R, Olsson A, Brüske I, Wichmann HE, Stücker I, Guida F, Tardón A, Merletti F, Mirabelli D, Richiardi L, Pohlabeln H, Ahrens W, Landi MT, Caporaso N, Consonni D, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Gustavsson P, Marcus M, Fabianova E, 't Mannetje A, Pearce N, Tse LA, Yu IT, Rudnai P, Bencko V, Janout V, Mates D, Foretova L, Forastiere F, McLaughlin J, Demers P, Bueno-de-Mesquita B, Boffetta P, Schüz J, Straif K, Pesch B, Brüning T. Welding and lung cancer in a pooled analysis of case-control studies. Am J Epidemiol 2013;178(10):1513-25.
  11. Olsson AC, Gustavsson P, Kromhout H, Peters S, Vermeulen R, Brüske I, Pesch B, Siemiatycki J, Pintos J, Brüning T, Cassidy A, Wichmann HE, Consonni D, Landi MT, Caporaso N, Plato N, Merletti F, Mirabelli D, Richiardi L, Jöckel KH, Ahrens W, Pohlabeln H, Lissowska J, Szeszenia-Dabrowska N, Zaridze D, Stücker I, Benhamou S, Bencko V, Foretova L, Janout V, Rudnai P, Fabianova E, Dumitru RS, Gross IM, Kendzia B, Forastiere F, Bueno-de-Mesquita B, Brennan P, Boffetta P, Straif K. Exposure to diesel motor exhaust and lung cancer risk in a pooled analysis from case-control studies in Europe and Canada. Am J Respir Crit Care Med 2011;183(7):941-8.
  12. Olsson AC, Xu Y, Schüz J, Vlaanderen J, Kromhout H, Vermeulen R, Peters S, Stücker I, Guida F, Brüske I, Wichmann HE, Consonni D, Landi MT, Caporaso N, Tse LA, Yu IT, Siemiatycki J, Richardson L, Mirabelli D, Richiardi L, Simonato L, Gustavsson P, Plato N, Jöckel KH, Ahrens W, Pohlabeln H, Tardón A, Zaridze D, Marcus MW, 't Mannetje A, Pearce N, McLaughlin J, Demers P, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Dumitru RS, Bencko V, Foretova L, Janout V, Boffetta P, Fortes C, Bueno-de-Mesquita B, Kendzia B, Behrens T, Pesch B, Brüning T, Straif K. Lung cancer risk among hairdressers: a pooled analysis of case-control studies conducted between 1985 and 2010. Am J Epidemiol 2013;178(9):1355-65.
  13. Olsson AC, Vermeulen R, Schüz J, Kromhout H, Pesch B, Peters S, Behrens T, Portengen L, Mirabelli D, Gustavsson P, Kendzia B, Almansa J, Luzon V, Vlaanderen J, Stücker I, Guida F, Consonni D, Caporaso N, Landi MT, Field J, Brüske I, Wichmann HE, Siemiatycki J, Parent ME, Richiardi L, Merletti F, Jöckel KH, Ahrens W, Pohlabeln H, Plato N, Tardón A, Zaridze D, McLaughlin J, Demers P, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Stanescu Dumitru R, Bencko V, Foretova L, Janout V, Boffetta P, Bueno-de-Mesquita B, Forastiere F, Brüning T, Straif K. Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies. Epidemiology 2017;28(2):288-299.
  14. Pesch B, Kendzia B, Gustavsson P, Jöckel KH, Johnen G, Pohlabeln H, Olsson A, Ahrens W, Gross IM, Brüske I, Wichmann HE, Merletti F, Richiardi L, Simonato L, Fortes C, Siemiatycki J, Parent ME, Consonni D, Landi MT, Caporaso N, Zaridze D, Cassidy A, Szeszenia-Dabrowska N, Rudnai P, Lissowska J, Stücker I, Fabianova E, Dumitru RS, Bencko V, Foretova L, Janout V, Rudin CM, Brennan P, Boffetta P, Straif K, Brüning T. Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer 2012;131(5):1210-9.
  15. Pesch B, Kendzia B, Hauptmann K, Van Gelder R, Stamm R, Hahn JU, Zschiesche W, Behrens T, Weiss T, Siemiatycki J, Lavoué J, Jöckel KH, Brüning T. Airborne exposure to inhalable hexavalent chromium in welders and other occupations: Estimates from the German MEGA database. Int J Hyg Environ Health 2015;218(5): 500-506
  16. Peters S, Kromhout H, Olsson AC, Wichmann HE, Brüske I, Consonni D, Landi MT, Caporaso N, Siemiatycki J, Richiardi L, Mirabelli D, Simonato L, Gustavsson P, Plato N, Jöckel KH, Ahrens W, Pohlabeln H, Boffetta P, Brennan P, Zaridze D, Cassidy A, Lissowska J, Szeszenia-Dabrowska N, Rudnai P, Fabianova E, Forastiere F, Bencko V, Foretova L, Janout V, Stücker I, Dumitru RS, Benhamou S, Bueno-de-Mesquita B, Kendzia B, Pesch B, Straif K, Brüning T, Vermeulen R. Occupational exposure to organic dust increases lung cancer risk in the general population. Thorax 2012;67(2):111-6.
  17. Peters S, Vermeulen R, Portengen L, Olsson A, Kendzia B, Vincent R, Savary B, Lavoué J, Cavallo D, Cattaneo A, Mirabelli D, Plato N, Fevotte J, Pesch B, Brüning T, Straif K, Kromhout H. SYN-JEM: A Quantitative Job-Exposure Matrix for Five Lung Carcinogens. Ann Occup Hyg 2016;60(7):795-811
  18. Taeger D, Pesch B, Kendzia B, Behrens T, Jöckel KH, Dahmann D, Siemiatycki J, Kromhout H, Vermeulen R, Peters S, Olsson A, Brüske I, Wichmann HE, Stücker I, Guida F, Tardón A, Merletti F, Mirabelli D, Richiardi L, Pohlabeln H, Ahrens W, Landi MT, Caporaso N, Pesatori AC, Mukeriya A, Szeszenia-Dabrowska N, Lissowska J, Gustavsson P, Field J, Marcus MW, Fabianova E, 't Mannetje A, Pearce N, Rudnai P, Bencko V, Janout V, Dumitru RS, Foretova L, Forastiere F, McLaughlin J, Paul Demers PD, Bueno-de-Mesquita B, Schüz J, Straif K, Brüning T. Lung cancer among coal miners, ore miners and quarrymen: smoking-adjusted risk estimates from the synergy pooled analysis of case-control studies. Scand J Work Environ Health 2015;41(5):467-77.
  19. Weiss T, Pesch B, Lotz A, Gutwinski E, Van Gelder R, Punkenburg E, Kendzia B, Gawrych K, Lehnert M, Heinze E, Hartwig A, Käfferlein HU, Hahn JU, Brüning T; WELDOX Group. Levels and predictors of airborne and internal exposure to chromium and nickel among welders--results of the WELDOX study. Int J Hyg Environ Health 2013;216(2): 175-183

 

Further Information