Elevated DEHP and Metabolic Susceptibility (MEHP%) Increase Breast Cancer Risk

What is it about?

Phthalates are widely used in various plastics, pharmaceuticals, and personal care items such as film formers, stabilizers, dispersants, lubricants, binders, emulsifying agents, viscosity control agents, gelling agents, and suspending agents. This prospective epidemiologic study in an East Asian cohort demonstrates that women with both high DEHP exposure and a high MEHP% have a significantly increased risk of breast cancer, establishing clear temporal causality. MEHP% represents the proportion of MEHP in total measured DEHP metabolites; a higher MEHP% potentially indicates limited metabolic conversion of MEHP into downstream phase II or III metabolites. MEHP% reflects metabolic susceptibility modulating DEHP-associated breast cancer risk. The study establishes a clear temporal link between exposure to di(2-ethylhexyl) phthalate (DEHP)—one of the most widely used plasticizers—and increased breast cancer risk in women, providing evidence supporting a causal relationship. The researchers also identified metabolic susceptibility (MEHP%) as a biomarker for assessing breast cancer risk. The study further found that women with high phthalate exposure, higher metabolic susceptibility, and early menarche (before age 14) face up to a sevenfold increase in breast cancer risk.

Featured Image

Photo by Angiola Harry on Unsplash

Photo by Angiola Harry on Unsplash

Why is it important?

*A 20-year follow-up study provides causal temporal evidence linking DEHP exposure to breast cancer *From environmental exposure to individual metabolic differences in breast cancer risk assessment We identified metabolic susceptibility (MEHP%) as a biomarker reflecting individual differences in DEHP metabolism. MEHP, the primary metabolite of DEHP, plays a critical role in DEHP metabolism and may be more toxic than its secondary or tertiary metabolites. MEHP% represents the proportion of MEHP in total measured DEHP metabolites; a higher MEHP% potentially indicates limited metabolic conversion of MEHP into downstream phase II or III metabolites. Women with elevated MEHP% were found to be at higher risk of developing breast cancer. The study showed that, when both phthalate exposure and MEHP% were high, breast cancer risk increased to 2.68 times that of the control group. When combined with early menarche (before age 14), the three factors demonstrated a strong synergistic effect, with breast cancer risk rising to 7.52 times that of women without these risk factors. These findings highlight the interaction between environmental DEHP exposure and individual metabolic susceptibility. MEHP% reflects individual differences in the body’s ability to metabolize phthalates. This pattern suggests higher metabolic susceptibility, where intrinsic factors (such as genetic variations, hormone levels, or ethnic differences) and individual environmental exposures (such as endocrine-disrupting chemicals, pollutants, dietary habits, or lifestyle factors) may impair further metabolism. Such metabolic variation may potentially make some women more susceptible to breast cancer even at similar exposure levels. These individual differences in DEHP metabolism highlight the need to consider metabolic variations in environmental health studies. Including MEHP% in risk assessments can facilitate the development of personalized prevention strategies and targeted monitoring.

Perspectives