Tumor expression of environmental chemical-responsive genes and breast cancer mortality | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

5932888

Reference Type

Journal Article

Title

Tumor expression of environmental chemical-responsive genes and breast cancer mortality

Author(s)

Aushev, V; Gopalakrishnan, K; Teitelbaum, SL; Parada, H; Santella, RM; Gammon, M; Chen, J

Year

2019

Is Peer Reviewed?

Yes

Journal

Endocrine-Related Cancer
ISSN: 1351-0088
EISSN: 1479-6821

Publisher

BioScientifica Ltd.

Location

BRISTOL

Volume

Issue

Page Numbers

843-851

Language

English

PMID

31593922

DOI

10.1530/ERC-19-0357

Web of Science Id

WOS:000499633700004

Abstract

Environmental phenols and phthalates are common ingredients in personal care products and some have been implicated in breast cancer progression. We have previously identified genes differentially expressed in response to low-dose exposure to diethyl phthalate (DEP) and methyl paraben (MPB) in a rat model. Herein we explore if these genes are associated with breast cancer mortality in humans.

STUDY DESIGN: We profiled MPB- and DEP- responsive genes in tumors by NanoString from a population-based cohort of 606 women with first primary breast cancer among whom 119 breast cancer-specific deaths occurred within 15+ years of follow-up. For each gene, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results were validated in two publicly available datasets.

RESULTS: From 107 DEP- and 77 MPB-responsive genes profiled, 44 and 30 genes, respectively, were significantly associated with breast cancer-specific mortality. Some top DEP-responsive genes are novel for breast cancer mortality, such as ABHD14B [for high-vs-low expression, HR 0.36, 95% CI: 0.2-0.5] and TMC4 [HR 0.37, 95% CI: 0.3-0.5]; top hits for MPB (SLC40A1 [HR 0.37, 95% CI: 0.3-0.5] and NTN4 [HR 0.39, 95% CI: 0.3-0.6]) are well-known predictors of breast cancer survival. PLEKHA6 was another novel survival predictor, sensitive to hormonal receptor status (HR 0.5, 95% CI 0.3-0.9 for hormonal receptor-positive and HR 3.2, 95% CI 1.7-6.2 for -negative group).

CONCLUSIONS: Tumor expression of DEP- and MPB-responsive genes is associated with breast cancer mortality, supporting that exposure to these chemicals may influence the progression of breast cancer.

Keywords

Breast; Estrogen receptor; Mammary gland; Oncology