Abstract
BACKGROUND: Despite advances in understanding genetic susceptibility to cancer, much of cancer heritability remains unidentified. At the same time, the makeup of industrial chemicals in our environment only grows more complex. This gap in knowledge on cancer risk has prompted calls to expand cancer research to the comprehensive, discovery-based study of nongenetic environmental influences, conceptualized as the "exposome." METHODS: Our scoping review aimed to describe the exposome and its application to cancer epidemiology and to study design limitations, challenges in analytical methods, and major unmet opportunities in advanced exposome profiling methods that allow the quantification of complex chemical exposure profiles in biological matrices. To evaluate progress on incorporating measurements of the exposome into cancer research, we performed a review of such "cancer exposome" studies published through August 2023. RESULTS: We found that only 1 study leveraged untargeted chemical profiling of the exposome as a method to measure tens of thousands of environmental chemicals and identify prospective associations with future cancer risk. The other 13 studies used hypothesis-driven exposome approaches that targeted a set of preselected lifestyle, occupational, air quality, social determinant, or other external risk factors. Many of the included studies could only leverage sample sizes with less than 400 cancer cases (67% of nonecologic studies) and exposures experienced after diagnosis (29% of studies). Six cancer types were covered, most commonly blood (43%), lung (21%), or breast (14%) cancer. CONCLUSION: The exposome is underutilized in cancer research, despite its potential to unravel complex relationships between environmental exposures and cancer and to inform primary prevention.