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Background: There is conflicting evidence of an association between cadmium exposure and prostate cancer (PC) mortality in the general population. Since most PCs are indolent, low grade and low stage tumors may mask associations. We assessed associations between ambient exposure to air cadmium and PC aggressiveness at diagnosis in the US.
Methods: We collected outcome data from the 2010 – 2014 Surveillance, Epidemiology, and End Results (SEER). Aggressiveness at diagnosis was defined as stage categorized as either metastatic or localized and Gleason grade as high or low. The 2011 National Air Toxics Assessment database provided county-level air cadmium concentrations. Odds Ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression comparing the 80^th to 20^th percentile of cadmium exposure and adjusted for age at diagnosis, sociodemographic status, smoking prevalence and overall air quality at the county-level and were stratified by race and degree of urbanization defined by Rural-Urban Continuum Codes (RUCC).
Results: The study cohort consisted of 230,540 cases from 493 counties. Overall, higher air cadmium exposure was associated with an increased likelihood of metastatic PC compared to localized PC (OR 1.02, CI 1.01–1.03) and higher Gleason grade at diagnosis (OR 1.01, CI 1.00–1.02). The strongest associations were observed in nonmetropolitan areas with urban populations of 20,000 to 250,000 (RUCC2 counties): (OR 1.26, CI 1.14–1.39) for metastatic vs. localized PC, and (OR 1.36, CI 1.25–1.49) for high vs. low grade cases.
Discussion: The strongest associations between air cadmium exposure and tumor aggressiveness were found among nonmetropolitan counties, where 40 million Americans reside. Research is necessary to identify air cadmium pollution sources in these communities and to rule out additional confounding factors. Air cadmium exposure in the general population may be a more important factor in prostate cancer and its progression than previously recognized.