Mapping the Human Exposome to Uncover the Causes of Breast Cancer

Abstract

Breast cancer is an important cause of morbidity and mortality for women, yet a significant proportion of variation in individual risk is unexplained. It is reasonable to infer that unexplained breast cancer risks are caused by a myriad of exposures and their interactions with genetic factors. Most epidemiological studies investigating environmental contribution to breast cancer risk have focused on a limited set of exposures and outcomes based on a priori knowledge. We hypothesize that by measuring a rich set of molecular information with omics (e.g., metabolomics and adductomics) and comparing these profiles using a case-control design we can pinpoint novel environmental risk factors. Specifically, exposome-wide association study approaches can be used to compare molecular profiles between controls and either breast cancer cases or participants with phenotypic measures associated with breast cancer (e.g., high breast density, chronic inflammation). Current challenges in annotating compound peaks from biological samples can be addressed by creating libraries of environmental chemicals that are breast cancer relevant using publicly available high throughput exposure and toxicity data, and by mass spectra fragmentation. This line of discovery and innovation will extend understanding of how environmental exposures interact with genetics to affect health, and provide evidence to support new breast cancer prevention strategies.

Keywords: adductomics; breast cancer; exposome; metabolomics.

Figure 1

Conceptual diagram. Exposome-wide association studies using a prospective case-control design can discover novel environmental risk factors related to breast cancer. The exposome includes measurements of a rich set of molecular information in prediagnostic biospecimens. Cases can be breast cancer cases or cases with phenotypic measures related to breast cancer.