Medical hypothesis: Hyperhomocysteinemia is a risk factor for estrogen-induced hormonal cancer

  • Authors:
    • Bao Ting Zhu
  • View Affiliations

  • Published online on: March 1, 2003     https://doi.org/10.3892/ijo.22.3.499
  • Pages: 499-508
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Abstract

A novel mechanistic hypothesis is proposed which suggests that hyperhomocysteinemia is a risk factor for the development of estrogen-induced hormonal cancer in humans. Mechanistically, hyperhomocysteinemia may exert its pathogenic effects largely through metabolic accumulation of intracellular S-adenosyl-L-homocysteine, a strong non-competitive inhibitor of the catechol-O-methyltransferase-mediated methylation metabolism of endogenous and exogenous catechol estrogens (mainly 2-hydroxyestradiol and 4-hydroxyestradiol). While a strong inhibition of the methylation metabolism of 2-hydroxyestradiol would decrease the formation of 2-methoxyestradiol (an antitumorigenic endogenous metabolite of 17β-estradiol), an inhibition of the methylation of 4-hydroxyestradiol would lead to accumulation of this hormonally-active and strongly procarcinogenic catechol estrogen metabolite. Both of these effects resulting from inhibition of the methylation metabolism of catechol estrogens would facilitate the development of estrogen-induced hormonal cancer in the target organs. This hypothesis also predicts that adequate dietary intake of folate, vitamin B6, and vitamin B12 may reduce hyperhomocysteinemia-associated risk for hormonal cancer. Experimental studies are warranted to determine the relations of hyperhomocysteinemia with the altered circulating or tissue levels of 4-hydroxyestradiol and 2-methoxyestradiol and also with the altered risk for estrogen-induced hormonal cancer.

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March 2003
Volume 22 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhu BT: Medical hypothesis: Hyperhomocysteinemia is a risk factor for estrogen-induced hormonal cancer. Int J Oncol 22: 499-508, 2003
APA
Zhu, B.T. (2003). Medical hypothesis: Hyperhomocysteinemia is a risk factor for estrogen-induced hormonal cancer. International Journal of Oncology, 22, 499-508. https://doi.org/10.3892/ijo.22.3.499
MLA
Zhu, B. T."Medical hypothesis: Hyperhomocysteinemia is a risk factor for estrogen-induced hormonal cancer". International Journal of Oncology 22.3 (2003): 499-508.
Chicago
Zhu, B. T."Medical hypothesis: Hyperhomocysteinemia is a risk factor for estrogen-induced hormonal cancer". International Journal of Oncology 22, no. 3 (2003): 499-508. https://doi.org/10.3892/ijo.22.3.499