8277626 Application of bias analysis: the case of socioeconomic status and lung cancer in a pooled international case-control study

<h3>Objective</h3> Socioeconomic status (SES) is an important confounder of the association between occupational exposures and lung cancer. However, the extent of SES effects on lung cancer, including mediating effects via smoking habits, remained unclear as several biases were often indicated. Therefore, we aimed to quantify the impact of potential biases on the SES-lung cancer association. <h3>Material and Methods</h3> We used data from the SYNERGY project (https://synergy.iarc.who.int), including 16,550 cases and 20,147 controls from European and Canadian case-control studies, to investigate bias effects in the association of occupational SES (in quartiles) and lung cancer. We estimated odds ratios (OR) with 95% confidence intervals (CI) by logistic regression adjusting for age, study centre, and smoking, stratified by sex. We also estimated natural direct SES effects and natural indirect effects via smoking by inverse odds ratio weighting. In a quantitative bias analysis, we considered impacts of misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic disposition, calculating 95% simulation intervals (SI) by bootstrap (n=2500 repetitions). <h3>Results</h3> Adjustment for smoking as well as natural effects estimation showed that nearly 50% of lung cancer risks for lower SES groups in men and up to one third in women were attributable to smoking. Consideration of all types of bias reduced lung-cancer risks in the fully adjusted logistic regression models: For the 4th versus 1st (highest) SES quartile OR decreased from 1.83 (1.69-1.98 CI) to 1.50 (1.32-1.69 SI) in men, and OR 1.48 (1.27-1.72 CI) to 1.20 (1.01-1.45 SI) in women. <h3>Conclusion</h3> Direct lung-cancer risks of lower SES groups were lowered by multiple bias adjustment but remained elevated. As long as it remains unclear to what extent these effects are attributable to occupational hazards, SES should be considered in the analysis of occupational exposures and lung cancer.