Prenatal exposure to polycyclic aromatic hydrocarbons and altered DNA methylation in breast cancer-related genes

Background/Purpose: Minority populations, particularly young African American women, bear a disproportionate burden of more aggressive breast cancer subtypes. These racial/ethnic disparities can be partially explained by the distribution of risk factors, including urban environmental exposures. Polycyclic aromatic hydrocarbons (PAH) are widespread carcinogenic and hormonally active environmental contaminants with disproportionately high exposure in urban low income and/or communities of racial and ethnic minorities. In our Columbia9s Children Center for Environmental Health (CCCEH) birth cohort, prenatal PAH exposure has been associated with lower global DNA methylation in umbilical cord white blood cells (WBC). We extend this work to examine whether prenatal PAH exposure is associated with altered WBC DNA methylation in genes associated with breast cancer risk, including DNA repair, growth, and age at menarche. Methods: CCCEH enrolled nonsmoking African-American and Dominican pregnant women in New York City between 1998 and 2006 and followed their children through 9 years of age. We examined measures of PAH exposure through two primary sources: 1) prospective maternal personal air monitoring in the third trimester of pregnancy, and 2) PAH-DNA adducts measured in maternal blood at delivery and umbilical cord blood. We examined differences in WBC DNA methylation in 21 candidate genes in 223 girls (ages 7 or 9 years) by prenatal PAH exposure using targeted massively parallel bisulfite sequencing. For each amplicon, we used multivariable linear regression models to assess the association of DNA methylation and the three measures of prenatal PAH exposure. We adjusted all models for girls9 age and race/ethnicity and tested for confounding by socioeconomic and reproductive variables and having a smoker in the house prenatally and at year 7 or 9. The sum levels of eight airborne PAH were analyzed as a log-transformed continuous variable (n=223). PAH-DNA adducts in maternal (n=185) and cord blood (n=115) were categorized as below the limit of detection (reference), and above and below the median in those with detectible adducts. Results: We found significantly different methylation levels by ethnicity in five candidate genes; we did not observe varied methylation by girls9 age or BMI at the time of blood collection. We observed evidence of decreased methylation in DNA repair gene BRCA1 (Δ = -2.3, p-value 0.06) with increasing airborne PAH levels. For cord blood PAH-DNA adducts, compared to those with non-detectable adducts, we observed decreased methylation in an imprinted gene associated with breast cancer and body weight regulation, H19 (Δ = -6.5, p-value 0.001) in girls with the highest level of detectable adducts (above the median in those with detectable adducts). Conclusions: Preliminary findings from this urban cohort suggest that measures of prenatal exposure to PAH may result in altered methylation in genes related to breast cancer risk and body weight in young girls. Citation Format: Nur Zeinomar, Hui-Chen Wu, Xinran Ma, Julie B. Herbstman, Frederica P. Perera, Rachel L. Miller, Mary Beth Terry. Prenatal exposure to polycyclic aromatic hydrocarbons and altered DNA methylation in breast cancer-related genes [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C082.