Parabens are a group of alkyl
esters of p-
hydroxybenzoic acid added to consumer products to prevent the growth of harmful bacteria and molds.
Parabens are hypothesized to increase the risk of
breast cancer (BC); however, no study has examined the interactions between
parabens, global DNA methylation (DNAm), and BC risk. We examined the modifying effects of DNAm on the associations between
parabens and BC, and whether
parabens were associated with BC defined by
tumor promoter methylation status. Participants included 708 cases and 598 controls from the Long Island Breast Cancer Study Project.
Methylparaben (MPB),
propylparaben, and butylparaben levels were measured in spot urine samples. Global DNAm was measured by analysis of long interspersed elementes-1 (LINE-1) and the luminometric methylation assay (LUMA). The promoter methylation status of 13 genes was measured in
tumor samples from 509 cases. We used logistic regression to estimate odds ratios (
ORs) and 95% confidence intervals (CIs) for the associations between
parabens and BC stratified by LINE-1/LUMA, and between
parabens and gene-specific promoter methylation-defined BC. Outcome heterogeneity was evaluated using ratios of
ORs (RORs). We assessed the joint effects of the multiple
parabens using quantile g-computation. The highest versus lowest tertile of MPB and a one-quantile increase in all
parabens were associated with
ORs of 1.46 (95% CI = 0.96-2.23) and 1.32 (95% CI = 1.02-1.71), respectively, among women with hypomethylated LINE-1. A one-ln unit increase in MPB was associated with a 25% increase in the odds of hypomethylated (vs. hypermethylated) CCND2 promoter-defined BC (ROR = 1.25, 95% CI = 1.06-1.48), and a one-quantile increase in all
parabens was associated with a 55% increase in the odds of hypomethylated (vs. hypermethylated) CCND2 promoter-defined BC (ROR = 1.55, 95% CI = 1.04-2.32). Exposure to
parabens may increase the risk of BC among women with hypomethylated global DNAm and may increase the risk of
tumors with gene-specific hypomethylated promoter regions.