NDLI: Role of cytochrome P450 genes in breast cancer etiology and treatment: effects on estrogen biosynthesis, metabolism, and response to endocrine therapy

Content Provider	Springer Nature Link
Author	Blackburn, Heather L. Ellsworth, Darrell L. Shriver, Craig D. Ellsworth, Rachel E.
Copyright Year	2014
Abstract	The cytochrome P450 (CYP) genes are oxygenases involved in estrogen biosynthesis and metabolism, generation of DNA damaging procarcinogens, and response to anti-estrogen therapies. Since lifetime estrogen exposure is an established risk factor for breast cancer, determining the role of CYP genes in breast cancer etiology may provide critical information for understanding tumorigenesis and response to treatment.This review summarizes literature available in PubMed published between 1993 and 2013 that focuses on studies evaluating the effects of DNA variants in CYP genes on estrogen synthesis, metabolism, and generation of procarcinogens in addition to response to anti-estrogen therapies.Evaluation of DNA variants in estrogen metabolism genes was largely inconclusive. Meta-analyses of data from CYP19A1 support an association between the number of (TTTA) n repeats in intron 4 and breast cancer risk, but the biological mechanism for this relationship is unknown. Associations between single nucleotide polymorphism in CYP1B1 and DNA damage caused by procarcinogenic estrogen metabolites were ambiguous. Variants in CYP2D6 are associated with altered metabolism tamoxifen; however, current data do not support widespread clinical testing. The effect of variants in CYP19A1 in response to aromatase inhibitors is also questionable.Evaluation of DNA variants in CYP genes involved with estrogen metabolism or treatment response has been inconclusive, reflecting small samples sizes, tumor heterogeneity, and differences between populations. Better-powered studies that account for genetic backgrounds and tumor phenotypes are thus necessary.
Starting Page	319
Ending Page	332
Page Count	14
File Format	PDF
ISSN	09575243
Journal	Cancer Causes & Control
Volume Number	26
Issue Number	3
e-ISSN	15737225
Language	English
Publisher	Springer International Publishing
Publisher Date	2015-01-03
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cytochrome P450 Breast cancer Estrogen biosynthesis and metabolism Procarcinogen Drug metabolism Cancer Research Biomedicine general Oncology Public Health Epidemiology Hematology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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