Hormonal carcinogenesis

Henderson, Brian E.; Feigelson, Heather Spencer

doi:10.1093/carcin/21.3.427

Cited by 821Estrogen and related hormone effectsBRCA gene mutations in cancerCancer Risks and Factors

Hormonal carcinogenesis

Henderson, Brian E., Feigelson, Heather Spencer·2000·Carcinogenesis

DOI 10.1093/carcin/21.3.427

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Abstract

Hormone-related cancers, namely breast, endometrium, ovary, prostate, testis, thyroid and osteosarcoma, share a unique mechanism of carcinogenesis. Endogenous and exogenous hormones drive cell proliferation, and thus the opportunity for the accumulation of random genetic errors. The emergence of a malignant phenotype depends on a series of somatic mutations that occur during cell division, but the specific genes involved in progression of hormone-related cancers are currently unknown. In this review, the epidemiology of endometrial cancer and breast cancer are used to illustrate the paradigms of hormonal carcinogenesis. Then, new strategies for early detection and prevention of hormonal carcinogenesis are discussed. This includes developing polygenic models of cancer predisposition and the further development of safe and effective chemopreventives that block target sequence activity. We developed polygenic models for breast and prostate cancer after hypothesizing that functionally relevant sequence variants in genes involved in steroid hormone metabolism and transport would act together, and also interact with well-known hormonally related risk factors, to define a high-risk profile for cancer. A combination of genes each with minor variation in expressed activity could provide a degree of separation of risk that would be clinically useful as they could yield a large cumulative difference after several decades. The genes included in the breast cancer model are the 17beta-hydroxysteroid dehydrogenase 1 (HSD17B1) gene, the cytochrome P459c17alpha (CYP17) gene, the aromatase (CYP19) gene, and the estrogen receptor alpha (ER) gene. The prostate cancer model includes the androgen receptor gene (AR), steroid 5alpha-reductase type II (SRD5A2), CYP17 and the 3beta hydroxysteroid dehydrogenase (HSD3B2) gene. We present data from our multi-ethnic cohort to support these models.

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Authors: Henderson, B. E., & Feigelson, H. S.
Affiliations: University of Southern California (US)
ORCID: Feigelson, Heather Spencer
Venue: Carcinogenesis
Publisher: Oxford University Press (OUP)
Published: 2000-03
Volume: 21
Issue: 3
Pages: 427-433
ISSN: 0143-3334 (ISSN-L)
1460-2180
DOI: 10.1093/carcin/21.3.427
OpenAlex: W4235221123
Cited by: 821
References: 47
Citations by year: 2026: 7 · 2025: 23 · 2024: 36 · 2023: 39 · 2022: 28 · 2021: 35 · 2020: 27 · 2019: 19 · 2018: 23 · 2017: 24 · 2016: 35 · 2015: 38 · 2014: 32 · 2013: 29 · 2012: 36
FWCI: 4.17
Type: journal article
Language: en
Open access: closed
Locations: Carcinogenesis (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Health Sciences › Medicine › Oncology › Cancer Risks and Factors
Keywords: hormonal carcinogenesis, hormone-dependent tumors, breast cancer, endometrial cancer, prostate cancer, chemoprevention, 17β-hydroxysteroid dehydrogenase 1, CYP17, aromatase, estrogen receptor alpha, androgen receptor, SRD5A2, HSD3B2, somatic mutations, cancer risk stratification
MeSH terms: Breast Neoplasms, Female, Hormones, Humans, Neoplasms, Hormone-Dependent, Endometrial Neoplasms

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Hormonal carcinogenesis

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