Estrogen receptor beta as target for colorectal cancer prevention

Cecilia Williams, Alfredo DiLeo, Yaron Niv, Jan Åke Gustafsson

Research output: Contribution to journalReview article

78 Scopus citations

Abstract

Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive approaches are not sufficient. However, a role for estrogen has been demonstrated in multiple epidemiologic studies, which may benefit CRC prevention. A large body of evidence from preclinical studies indicates that expression of the estrogen receptor beta (ERβ/ESR2) demonstrates an inverse relationship with the presence of colorectal polyps and stage of tumors, and can mediate a protective response. Natural compounds, including phytoestrogens, or synthetic ERβ selective agonists, can activate or upregulate ERβ in the colon and promote apoptosis in preclinical models and in clinical experience. Importantly, this activity has been associated with a reduction in polyp formation and, in rodent models of CRC, has been shown to lower incidence of colon adenocarcinoma. Collectively, these findings indicate that targeted activation of ERβ may represent a novel clinical approach for management of colorectal adenomatous polyps and prevention of colorectal carcinoma in patients at risk for this condition. In this review, we discuss the potential of new chemopreventive or dietary approaches based on estrogen signaling.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalCancer Letters
Volume372
Issue number1
DOIs
StatePublished - Mar 1 2016

Keywords

  • Colorectal cancer
  • Estrogen
  • Estrogen receptor beta
  • Gene expression
  • Phytoestrogens
  • Prevention

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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