Chemical-responsive genes and breast cancer risk

Aushev et al. investigated whether the expression of certain genes, previously shown in animal models to be responsive to common ingredients in personal care products, have a relationship with breast cancer survival.  These ingredients have been associated with the development and progression of breast cancer, though human research on this topic is scarce.

The researchers previously used a rat model to show that a low dose of methyl paraben, MPB, a antimicrobial agent in cosmetics, foods and pharmaceutical products, or diethyl phthalate, DEP, a type of phthalate used in many consumer products, especially fragrance-containing ones, administered at critical windows of development, changes the way that the mammary gland tissues in the breast develop. They found that when mammary glands are exposed to MPB and DEP, an altered pattern of gene expression is observed in the gland compared to untreated rats.

In this recent study, the researchers utilized a follow up cohort from the Long Island Breast Cancer Study Project, comprised of women newly diagnosed with primary breast cancer between August 1, 1996 and July 31, 1997, who lived in Nassau or Suffolk counties on Long Island. The authors used the National Death Index to categorize deaths based on whether or not they were associated with breast cancer.  The researchers then analyzed the expression of the MPB- and DEP-responsive genes identified in the animal studies in tumors from 606 women in the cohort, among whom 119 had died from breast cancer within 15+ years of diagnosis.  The presence of the MPB and DEP gene expression signatures was compared to cause of death.

The study found significant associations for approximately 40% of the genes examined, with the majority of the results indicating that higher gene expression of both types of chemical responsive genes was related to an increase in cancer deaths. These associations were largely confirmed in two independent publically available datasets. There were also some genes (mainly associated with exposure to parabens) that were associated with lower breast cancer mortality or longer survival.

To the authors’ knowledge, this is the first study establishing a link between DEP- and MPB-responsive genes and breast cancer survival.  These results shed some light on possible mechanisms related to breast cancer mortality.  They caution that additional human studies are needed to address this link more directly.

Aushev V, Gopalakrishnan K, Teitelbaum SL, Parada H, Santella RM, Gammon M, Chen J.  Tumor expression of environmental chemical-responsive genes and breast cancer mortality.   Endocr Relat Cancer. 2019 Oct 1. pii: ERC-19-0357. doi: 10.1530/ERC-19-0357. [Epub ahead of print]  PMID: 31593922.

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