Abstract
Despite their ubiquitous expression, the inheritance of monoallelic germline mutations in breast cancer susceptibility gene type 1 or 2 (BRCA1/2) poses tissue-specific variations in cancer risks and primarily associate with familial breast and ovarian cancers. The molecular basis of this tissue-specific tumor incidence remains unknown and intriguing to cancer researchers. A plethora of recent reports support the idea that several nongenetic factors present in the tissue microenvironment could induce tumors in the mutant BRCA1/2 background. This Opinion article summarizes the recent advances on tissue-specific carcinogens and their complex crosstalk with the compromised DNA repair machinery of BRCA1/2-mutant cells. Finally, we present our perspective on the therapeutic and chemopreventive interpretations of these developments.
Keywords:
BRCA1; BRCA2; carcinogens; hereditary cancers.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Aldehydes / metabolism
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Androgens / metabolism
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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BRCA1 Protein / genetics
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BRCA1 Protein / metabolism
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BRCA2 Protein / genetics
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BRCA2 Protein / metabolism
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Bicarbonates / metabolism
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Breast / pathology
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Carcinogenesis / genetics
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Carcinogenesis / pathology
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Carcinogens / metabolism*
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DNA Breaks, Double-Stranded
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DNA Repair / drug effects
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Estrogens / metabolism
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Female
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Genetic Predisposition to Disease
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Hereditary Breast and Ovarian Cancer Syndrome / drug therapy
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Hereditary Breast and Ovarian Cancer Syndrome / genetics
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Hereditary Breast and Ovarian Cancer Syndrome / pathology*
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Hereditary Breast and Ovarian Cancer Syndrome / prevention & control
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Humans
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Male
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Mutation
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Ovary / pathology
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Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
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Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
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Prostate / pathology
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / pathology*
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Prostatic Neoplasms / prevention & control
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Reactive Nitrogen Species / metabolism
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Reactive Oxygen Species / metabolism
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Tumor Microenvironment / drug effects*
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Tumor Microenvironment / genetics
Substances
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Aldehydes
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Androgens
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Antioxidants
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BRCA1 Protein
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BRCA1 protein, human
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BRCA2 Protein
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BRCA2 protein, human
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Bicarbonates
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Carcinogens
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Estrogens
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Poly(ADP-ribose) Polymerase Inhibitors
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Reactive Nitrogen Species
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Reactive Oxygen Species