Importance of reference group selection in the evaluation of cancer incidence

Elevated cancer incidence has been reported among World Trade Center (WTC)-exposed responders, with some incidence rate ratios (IRRs) varying over time. This study describes the influence that different reference populations have on relative cancer incidence and temporal trends. Participants from the WTC Combined Rescue/Recovery Cohort (n = 65,691) were observed between 1/1/2002 and 12/31/2015 using data obtained from 13 state cancer registries. Poisson regression was used to estimate IRRs controlling for age, race/ethnicity, and calendar year. IRRs and change-points were estimated using three reference populations (New York City (NYC), New York State (NYS), and a US population). IRRs for each cancer site varied in magnitude. Prostate and thyroid cancer IRRs were significantly greater in WTC-exposed responders, while colon and lung cancer IRRs were significantly lower compared with NYC, NYS, and US population reference groups. The range of IRRs varied by reference population. Mixed findings were observed for other cancers, as results were dependent on the reference group used. A significant change-point was found only for prostate cancer, and only when compared to a US population. Our findings suggest that reference population selection will influence the IRR, timing, and statistical significance of change-point estimation, varying with follow-up length.