TY - JOUR
T1 - Urinary parabens and breast cancer risk
T2 - Modification by LINE-1 and LUMA global DNA methylation, and associations with breast cancer defined by tumor promoter methylation status
AU - Parada, Humberto
AU - Sahrai, Leili
AU - Wolff, Mary S.
AU - Santella, Regina M.
AU - Chen, Jia
AU - Neugut, Alfred I.
AU - Teitelbaum, Susan L.
N1 - Funding Information:
Dr. Neugut has consulted for Otsuka, GlaxoSmithKline, Eisai, Hospira, and United Biosource Corp., and has grant support from Otsuka. He serves on the medical advisory board of EHE Intl. The remaining authors declare no conflict of interest.
Funding Information:
We acknowledge the principal investigator of the Long Island Breast Cancer Study Project: Marilie D. Gammon, without whom this project would not be accomplished. We also acknowledge Antonia Calafat and the National Center for Environmental Health at the Centers for Disease Control and Prevention for support in measuring the urinary concentrations of paraben biomarkers. The Long Island Breast Cancer Study Project (LIBCSP) was supported in part by funds from the National Cancer Institute and the National Institute of Environmental Health Sciences (U01 CA/ES66572, U01 CA66572), and by the Babylon Breast Cancer Coalition. H. Parada Jr was supported by the National Cancer Institute (K01 CA234317), the SDSU/UCSD Comprehensive Cancer Center Partnership (U54 CA132384 and U54 CA132379), and the Alzheimer's Disease Resource Center for advancing Minority Aging Research at the University of California San Diego (P30 AG059299).
Funding Information:
We acknowledge the principal investigator of the Long Island Breast Cancer Study Project: Marilie D. Gammon, without whom this project would not be accomplished. We also acknowledge Antonia Calafat and the National Center for Environmental Health at the Centers for Disease Control and Prevention for support in measuring the urinary concentrations of paraben biomarkers. The Long Island Breast Cancer Study Project (LIBCSP) was supported in part by funds from the National Cancer Institute and the National Institute of Environmental Health Sciences (U01 CA/ES66572, U01 CA66572), and by the Babylon Breast Cancer Coalition. H. Parada Jr was supported by the National Cancer Institute (K01 CA234317), the SDSU/UCSD Comprehensive Cancer Center Partnership (U54 CA132384 and U54 CA132379), and the Alzheimer's Disease Resource Center for advancing Minority Aging Research at the University of California San Diego (P30 AG059299).
Publisher Copyright:
© 2022 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - DNA methylation
KW - breast cancer
KW - endocrine disrupting chemicals
KW - gene promoter methylation
KW - parabens
UR - http://www.scopus.com/inward/record.url?scp=85135966866&partnerID=8YFLogxK
U2 - 10.1002/mc.23456
DO - 10.1002/mc.23456
M3 - Article
AN - SCOPUS:85135966866
VL - 61
SP - 1002
EP - 1015
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 11
ER -