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The Triad of Estrogen, Estrogen Receptors, and Colon Cancer

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Colon Cancer Diagnosis and Therapy Vol. 3

Abstract

Colon cancer is one of the common malignancies in the developed world irrespective of the sexes. The incidence of colon cancer is increasing leaps and bounds in the developing world also during the past few decades. Several risk factors including diet, environmental triggers, sedentary life style, and genetic susceptibility are known to predispose an individual for the development of colon cancer. Sex hormone estrogen plays a major role in various metabolic processes in the body, and deficiency in the levels of estrogen is reported to be a primary causative factor in the pathogenesis of many diseases including postmenopausal osteoporosis, cardiovascular disease, immune dysfunction, and many others. On the contrary, estrogens are also proven to exert a proproliferative effect in the reproductive organs, thereby establishing their role in the development of breast and endometrial cancers. Interestingly, hormone replacement therapy with estrogen is proven to reduce the risk of colorectal cancer (CRC) in postmenopausal women. Estrogen exerts its action by binding with nuclear receptors ERα and ERβ and also through binding with the membrane bound G-protein coupled estrogen receptor (GPER). Recent research has proven that the distribution of nuclear estrogen receptors alpha and beta in different organs and the preferential binding of estrogen to either of these receptors might be instrumental in determining the crucial switch between procarcinogenic and anticarcinogenic effects of estrogen. Reduced expression of the nuclear estrogen receptor beta in the colon is reported to enhance the risk of an individual for the development of CRC. This implicates the usefulness of estrogen receptor β expression as a reliable prognostic and diagnostic marker for CRC. In short, clinical endocrine therapies based on the estrogen-regulated expression of estrogen receptors, development of tissue selective estrogen receptor modulators, and phytoestrogen-based diets can all play a pivotal role in the prevention and therapy of colon cancer in the future. This chapter discusses the influence of estrogen and its constituent receptors in the development of colon cancers and as to how these can be exploited in the diagnosis, to monitor prognosis and to plan therapeutic regimes for the management of malignancies of the colon.

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Abbreviations

CIMP:

CpG island methylator phynotype

CIN:

Chromosomal instability

CRC:

colorectal cancer

ER:

Estrogen receptor

ERE:

Estrogen responsive elements

FPA:

Familial adenomatous polyposis

GPER:

G-protein coupled estrogen receptor

HNPCC:

Hereditary nonpolyposis colorectal cancer

SERD:

Selective estrogen receptor degrader

SERM:

Selective estrogen receptor modulator

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Acknowledgments

The authors thank the University Grants Commission (UGC), Government of India, for the financial assistance provided to the Department of Microbiology and Biotechnology, Bangalore University, Bangalore, in the form of Special Assistance Programme (SAP)-DRS II which provided support for extensive literature survey and procurement of stationery material and to incur expenditure toward printing and photocopying charges for writing this chapter. Dr. SK acknowledges the financial assistance provided by UGC, GOI, in the form of postdoctoral fellowship (Dr. D.S. Kothari-PDF).

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Sumalatha, K.R., Soumyakrishnan, S., Sreepriya, M. (2022). The Triad of Estrogen, Estrogen Receptors, and Colon Cancer. In: Shukla, D., Vishvakarma, N.K., Nagaraju, G.P. (eds) Colon Cancer Diagnosis and Therapy Vol. 3. Springer, Cham. https://doi.org/10.1007/978-3-030-72702-4_3

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