The need for a cancer exposome atlas: a scoping review

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.

Graphical Abstract

Figure 1.

Diagram of select characteristics and mechanisms of environmental chemical carcinogens demonstrating their complexity for research study design. Note: This is not comprehensive of all physiological mechanisms.

Figure 2.

Flow chart of number of studies screened, excluded, and assessed in our scoping review.

Figure 3.

Case counts, cancer type, exposure types, and exposure methodological approach for the 14 cancer exposome studies analyzed in this scoping review. Points are labeled with the cancer type: Br = breast, Pr = prostate, Lu = lung, Le = leukemia, Ly = lymphoma, Co = colorectal. Notes: For ecologic study designs in two papers, the number of cases was treated as the number of sampled regions. For exposure type, the primary focus was chosen.

Figure 4.

Summary of study designs and time period that exposure data reflects relative to cancer outcome occurrence for the 14 eligible studies included in our scoping review. Note: One study with cross-sectional exposure data at time of outcome also asked about pre-outcome factors.

Figure 5.

Research needs and study design considerations for the cancer exposome. Note: icons are for illustration purposes and not intended to be comprehensive. Here, the external exposome refers to environmental stressors occurring outside the body, while the internal exposome refers to biomarkers of internalized exposures to those environmental stressors.