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, 105 kB)

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