Estrogen receptor beta as target for colorectal cancer prevention

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

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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
Pages (from-to)48-56
Number of pages9
JournalCancer Letters
Issue number1
StatePublished - 1 Mar 2016


FundersFunder number
Robert A. Welch FoundationE-0004
National Institutes of Health
National Cancer InstituteR01CA172437
Texas Emerging Technology Fund300-9-1958
Marie CurieGROWTH 291795


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


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