Epigenetics and epidemiology: models of study and examples.

Area of Science:

• Environmental epidemiology
• Biomarker research
• Endocrinology

Background:

• Epidemiological studies identify environmental disease causes but face methodological limitations like exposure assessment issues and confounding.
• Mendelian randomization and the meet-in-the-middle (MITM) approach are proposed to enhance observational study validity.
• The MITM approach integrates -omics data to identify intermediate biomarkers linking environmental exposures to disease outcomes.

Purpose of the Study:

• To introduce and exemplify the meet-in-the-middle (MITM) approach for investigating environmental exposures and disease.
• To explore the potential causal association between endocrine disruptors and breast cancer using the MITM framework.
• To review existing literature to illustrate the application of MITM in endocrine disruptor-breast cancer research.

Main Methods:

• The MITM approach involves three steps: 1. Association between exposure and disease. 2. Association between exposure (or its biomarkers) and intermediate -omic biomarkers. 3. Association between disease outcome and intermediate -omic biomarkers.
• Literature review to identify studies relevant to endocrine disruptors, breast cancer, and potential intermediate biomarkers.
• Application of the MITM framework to assess the strength of evidence for a causal link.

Main Results:

• The MITM approach provides a structured method to evaluate potential causal relationships by triangulating evidence across exposure, biomarkers, and disease.
• Preliminary literature suggests associations that, when assessed through the MITM lens, may strengthen or weaken the hypothesis of endocrine disruptors causing breast cancer.
• The review highlights the utility of -omics data in dissecting complex etiological pathways.

Conclusions:

• The MITM approach offers a robust framework for improving the causal inference in environmental epidemiology, particularly for complex diseases like breast cancer.
• Further research applying the MITM approach is warranted to elucidate the role of specific endocrine disruptors in breast cancer etiology.
• -Omics technologies are crucial for advancing our understanding of environmental health and disease mechanisms.