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Women exposed to chemicals in food packaging, dyes and personal care products may face an increased risk of developing certain cancers including ovarian, uterine and breast cancers, according to a study published Monday in the Journal of Exposure Science & Environmental Epidemiology.

The study identified the main cancer-causing chemical culprits as per- and polyfluoroalkyl substances (PFAS), phenols and phenol-related parabens — found in thousands of household and industrial products, especially in stain- and heat-resistant items and packaging.

Researchers did not uncover any clear associations between most cancers and chemical exposure in men.

In fact, exposure to PFAS and phenols/parabens were negatively associated with melanoma in men: the greater the levels in blood and urine, the lower the incidence of skin cancer.

However, the study did find that Hispanic men with a previous prostate cancer diagnosis were more likely than white men to have higher levels of one type of PFAS.

This is not to say that PFAS and phenols protect men from prostate cancer, any more than that they cause cancer in women. The study was not designed to test causal relationships, which would have required first measuring chemical levels and then following subjects for many years to see if they developed cancer.

Matching exposure levels to various cancers

Researchers, led by Max Aung, Ph.D., MPH, of the University of Southern California’s Keck School of Medicine, examined data from more than 10,000 people ages 20 or older.

The data were collected from 2005-2018 through the National Health and Nutrition Examination Survey (NHANES), a Centers for Disease Control and Prevention surveillance program.

Their analysis focused on 7 PFAS and 12 phenols/parabens, correlating blood and urine levels of those chemicals with self-reported prior occurrences in men and women of melanoma and cancers of the thyroid, breast, ovary, uterus and prostate.

Chemical levels fell into four exposure levels, which investigators matched against occurrences of various cancers. They made further correlations to white and non-white ethnicities.

Women with higher exposure to three specific PFAS — PFDE, PFNA and PFUA — were twice as likely to report a prior melanoma diagnosis. A somewhat weaker link between PFNA and uterine cancer was also evident.

Women who reported a previous melanoma diagnosis were more likely to fall into higher exposure level categories for 3 PFAS and 3 phenols, with risks ranging from 72% to 102% higher.

Previous ovarian cancer was associated with higher levels of three phenols, with risks ranging from 76% to 180% higher. Previous uterine cancer was associated with higher levels of one PFAS.

Higher PFAS levels were associated with ovarian or uterine cancers in white women but with breast cancer among non-white women.

Investigators also noted a racial component to the PFAS-cancer connection. Reproductive (ovarian and uterine) cancers occurred mostly in exposed white women, while the phenols-cancer link was most prominent in non-whites.

Dietary habits and proximity to contaminated drinking water could explain these differences, the authors said.

Why women but not men?

The association between chemical exposure and prior cancer diagnoses in women, but not in men, led investigators to surmise that PFAS and phenols are working through a sex-specific mechanism specifically involving estrogen.

This idea is controversial, however. One earlier test tube experiment showed that PFAS interfere with estrogen activity, while two others failed to find a connection in mice or cultured human cells.

PFAS disrupt hormone functions specific to women, which the study authors believed was the mechanism responsible for the possible increased risk.

Hormone-sensitive cancers are common but hard to treat, so prevention is the only way to lessen their impact.

But avoiding PFAS and phenols is nearly impossible because these chemicals are everywhere and persist in the environment for many years, earning them the moniker “forever chemicals.”

PFAS persist in water, soil, air and food. According to the U.S. Geological Survey, 45% of U.S. drinking water is contaminated with PFAS. Nearly all Americans have the chemicals in their blood.

The study was part of an ongoing project at the National Institutes of Environmental Health to understand the implications of exposure to common chemicals on human health.

More than 4,700 PFAS have been registered in the U.S. but millions of possible PFAS structures exist.

PFAS are synthetic molecules made in a production facility and do not occur in nature. Industrial phenols/parabens are also mostly synthetic but millions of related structures occur in nature.

This is a concern because synthetic chemicals resembling natural substances often accentuate or negate the effects of their beneficial counterparts.

Laying the groundwork for future studies

Aung and co-authors claimed theirs was “the first epidemiological study to investigate exposure to phenols in relation to previous cancer diagnoses, and the first NHANES study to explore racial/ethnic disparities in associations between environmental phenol, paraben, and PFAS exposures and historical cancer diagnosis.”

By demonstrating associations between specific cancers and distinct environmental exposures the Aung study laid the groundwork for future, long-term prospective studies that assess PFAS and phenol exposure first, and use that data to predict future cancer occurrence.

This could lead, albeit after many years, to policy or regulatory changes for how these chemicals are used.

The study also suggests strategies for studying the relationships between entire chemical classes and exposure-related health issues.

Researchers stressed that this study does not prove that exposure to PFAS and phenols always leads to cancer.

The study’s main weakness was its retrospective design, which limits conclusions to the level of association but not causality.

And since information on time-since-cancer-diagnosis was unavailable, researchers could not rule out the possibility that a cancer diagnosis might influence behavior or lifestyle in ways that affect exposure levels. For example, chemotherapy treatments might cause levels of PFAS and phenols in urine and blood to rise.

Additionally, researchers assumed that exposure at one time point accurately reflects historical exposure levels.

Again, this might not be true because cancer or cancer treatments might affect behavior and exposure, and how the body manages and disposes of “forever chemicals.”

Finally, the study relied on self-reporting of cancer occurrence and type. This is not a very serious issue for some cancers, like breast and prostate, which patients self-report accurately more than 90% of the time, and which were the most common cancers reported in this study by women and men, respectively.

Still, the authors suggested that future prospective studies use “gold-standard cancer diagnosis” to record outcomes. Gold standard diagnoses vary in detail for different cancers but all involve microscopic examination of tumor cells by a pathologist.