Exploratory profiles of phenols, parabens, and per- and poly-fluoroalkyl substances among NHANES study participants in association with previous cancer diagnoses

Abstract

Background: Some hormonally active cancers have low survival rates, but a large proportion of their incidence remains unexplained. Endocrine disrupting chemicals may affect hormone pathways in the pathology of these cancers.

Objective: To evaluate cross-sectional associations between per- and polyfluoroalkyl substances (PFAS), phenols, and parabens and self-reported previous cancer diagnoses in the National Health and Nutrition Examination Survey (NHANES).

Methods: We extracted concentrations of 7 PFAS and 12 phenols/parabens and self-reported diagnoses of melanoma and cancers of the thyroid, breast, ovary, uterus, and prostate in men and women (≥20 years). Associations between previous cancer diagnoses and an interquartile range increase in exposure biomarkers were evaluated using logistic regression models adjusted for key covariates. We conceptualized race as social construct proxy of structural social factors and examined associations in non-Hispanic Black, Mexican American, and other Hispanic participants separately compared to White participants.

Results: Previous melanoma in women was associated with higher PFDE (OR:2.07, 95% CI: 1.25, 3.43), PFNA (OR:1.72, 95% CI: 1.09, 2.73), PFUA (OR:1.76, 95% CI: 1.07, 2.89), BP3 (OR: 1.81, 95% CI: 1.10, 2.96), DCP25 (OR: 2.41, 95% CI: 1.22, 4.76), and DCP24 (OR: 1.85, 95% CI: 1.05, 3.26). Previous ovarian cancer was associated with higher DCP25 (OR: 2.80, 95% CI: 1.08, 7.27), BPA (OR: 1.93, 95% CI: 1.11, 3.35) and BP3 (OR: 1.76, 95% CI: 1.00, 3.09). Previous uterine cancer was associated with increased PFNA (OR: 1.55, 95% CI: 1.03, 2.34), while higher ethyl paraben was inversely associated (OR: 0.31, 95% CI: 0.12, 0.85). Various PFAS were associated with previous ovarian and uterine cancers in White women, while MPAH or BPF was associated with previous breast cancer among non-White women.

Impact statement: Biomarkers across all exposure categories (phenols, parabens, and per- and poly- fluoroalkyl substances) were cross-sectionally associated with increased odds of previous melanoma diagnoses in women, and increased odds of previous ovarian cancer was associated with several phenols and parabens. Some associations differed by racial group, which is particularly impactful given the established racial disparities in distributions of exposure to these chemicals. This is 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.

Fig. 1. Flow chart for building the final analytical datasets.

Sample size are indicated in green boxes for PFAS chemicals and blue boxes for phenols/parabens.

Fig. 2. Odds of each cancer type with an IQR increase in each PFAS chemical.

Effect estimates and 95% confidence intervals are reported among men (Panel A) and women (Panel B). Models adjust for age at the time of survey, cotinine, poverty-income ratio, race, education, body mass index, and an indicator variable for NHANES cycle.

Fig. 3. Odds of each cancer type with an IQR increase in each phenol/paraben chemical.

Effect estimates and 95% confidence intervals are reported among men (Panel A) and women (Panel B). Models adjust for age at the time of survey, cotinine, poverty-income ratio, race, education, body mass index, an indicator variable for NHANES cycle, and creatinine.

Fig. 4. Differential associations between PFAS exposures and previous cancer diagnosis by race among women.

Complete corresponding numerical data can be found in the supplementary materials “Supplemental_Tables 8–11.xlsx”. Forest plot reports the odds of each cancer outcome and 95% confidence interval with an IQR increase in PFAS chemical for each race. For each respective row of plots, estimates were generated utilizing subsets of data containing only white women and women of the specified race.

Fig. 5. Differential associations between phenol/paraben exposures and previous cancer diagnosis by race among women.

Complete corresponding numerical data can be found in the supplementary materials “Supplemental_Tables 8–11.xlsx”. Forest plot reports the odds of each cancer outcome and 95% confidence interval with an IQR increase in phenol/paraben for each race. For each respective row of plots, estimates were generated utilizing subsets of data containing only white women and women of the specified race.