Abstract
Environmental and lifestyle factors are believed to account for >80% of breast cancers; however, it is not well understood how and when these factors affect risk and which exposed individuals will actually develop the disease. While alcohol consumption, obesity, and hormone therapy are some known risk factors for breast cancer, other exposures associated with breast cancer risk have not yet been identified or well characterized. In this paper, it is proposed that the identification of blood epigenetic markers for personal, in utero, and ancestral environmental exposures can help researchers better understand known and potential relationships between exposures and breast cancer risk and may enable personalized prevention strategies.
Highlights
While 5%–10% of breast cancers are due to genetic mutations and an additional ~10% are considered familial, most breast cancers are thought to be due in large part to environmental and lifestyle factors [1–4]
More common exposures that have been linked to breast cancer risk, including hormone therapy, obesity, alcohol consumption, and insufficient physical activity [9], generally have relative risks less than 2.0, meaning that exposed individuals have less than a 2-fold higher risk compared to unexposed individuals [4]
Epigenetic markers may help to distinguish which individuals in an exposed population are more likely to develop disease, which is a severe limitation in our current understanding of how environmental exposures affect breast cancer risk
Summary
While 5%–10% of breast cancers are due to genetic mutations and an additional ~10% are considered familial, most breast cancers are thought to be due in large part to environmental and lifestyle factors (which will be collectively referred to as “exposures”) [1–4]. More common exposures that have been linked to breast cancer risk, including hormone therapy, obesity, alcohol consumption, and insufficient physical activity [9], generally have relative risks less than 2.0, meaning that exposed individuals have less than a 2-fold higher risk compared to unexposed individuals [4] This type of knowledge enables potential risk reduction by lifestyle modification. This paper discusses strategies for improving our ability to identify and characterize such risk factors, the first step being the identification of epigenetic biomarkers for exposures that can be used to estimate individuals’ environmental exposures in large cohort studies with archived blood DNA and long follow-up time. DNA methylation could serve as potential biomarkers for exposures, which would enable the study of exposures on health in long-term cohorts even if exposures data, blood, and urine samples are not available
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