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A novel role for estrogen-induced signaling in the colorectal cancer gender bias

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Abstract

Colorectal cancer (CRC) is a malignancy whose incidence is increasing globally, and there is a gender difference in the increasing risk. Evidence from hormone replacement therapy studies points to a role for circulating estrogens in suppressing the development of CRC. Estrogen receptor-β has been identified as a tumor suppressor, but other actions of estrogen may also contribute to the difference in CRC incidence between men and women. The KCNQ1/KCNE3 potassium channel is regulated by estrogen in order to modulate chloride secretion during the menstrual cycle; the effect of estrogen on the colon is to promote fluid conservation during the implantation window. KCNQ1 is also a tumor suppressor in CRC, and its sustained expression has been linked to suppression of the Wnt/β-catenin signaling pathway that contributes to CRC tumor progression. KCNQ1 regulation may represent a link between the normal physiological actions of estrogen in the colon and the hormone’s apparent tumor-suppressive effects in CRC development.

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Authors and Affiliations

  1. Royal College of Surgeons in Ireland School of Medicine, Perdana University, Jalan MAEPS, MARDI Complex, 43400, Serdang, Selangor, Malaysia

    Amirah A. Haziman, Shankarii Ravinderan, Thanggamalar Thangavelu & Warren Thomas

  2. Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland

    Warren Thomas

Authors
  1. Amirah A. Haziman
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  2. Shankarii Ravinderan
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  3. Thanggamalar Thangavelu
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  4. Warren Thomas
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Correspondence to Warren Thomas.

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Cooperation between the Perdana University and the Royal College of Surgeons in Ireland is covered by an Institutional Memorandum of Understanding. The research is a focused review and did not involve human participants or the use of animals; consequently, ethical approval and participant consent were not required.

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The authors declare that they have no conflicts of interest.

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Haziman, A.A., Ravinderan, S., Thangavelu, T. et al. A novel role for estrogen-induced signaling in the colorectal cancer gender bias. Ir J Med Sci 188, 389–395 (2019). https://doi.org/10.1007/s11845-018-1867-1

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  • DOI: https://doi.org/10.1007/s11845-018-1867-1

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