Molecular pathways: Estrogen pathway in colorectal cancer.

Afsaneh Barzi, Annika Medea Lenz, Melissa J Labonte, Heinz-Josef Lenz

Research output: Contribution to journalArticlepeer-review

124 Citations (Scopus)


Worldwide, colorectal cancer has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data support a role for estrogen and its receptors in the initiation and progression of colorectal cancer and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of colorectal cancer. In the Women's Health Initiative trial, use of HRT in postmenopausal women reduced the risk of colon cancer by 56% [95% confidence interval (CI), 0.38-0.81; P = 0.003]. A recent meta-analysis showed that in women, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03-0.35; P = 0.026). In this review, using the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of colorectal cancer. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT, or soy products, exerts its effects through preventing this loss. Thus, in the adenoma-to-carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of colorectal cancer depends on identification of susceptible colorectal cancer population(s). Thus, research to better understand the estrogen pathway is fundamental for clinical delivery of these agents.

Original languageEnglish
Article number10.1158/1078-0432.CCR-13-0325
Pages (from-to)5842-5848
Number of pages7
JournalClinical Cancer Research
Issue number21
Early online date21 Aug 2013
Publication statusPublished - 01 Nov 2013
Externally publishedYes


  • Animals
  • Colorectal Neoplasms
  • Estrogens
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Progesterone
  • Receptors, Estrogen
  • Signal Transduction
  • Translational Medical Research


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