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

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 17beta-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.

• Authors: Bao Ting Zhu
• Journal: International journal of oncology (Int J Oncol) Vol. 22 Issue 3 Pg. 499-508 (Mar 2003) ISSN: 1019-6439 [Print] Greece
• PMID: 12579301 (Publication Type: Journal Article)

Chemical References

• Anticarcinogenic Agents
• Catechol O-Methyltransferase Inhibitors
• Estrogens
• Estrogens, Catechol
• Estradiol
• Vitamin B 6
• Folic Acid
• S-Adenosylhomocysteine
• 2-hydroxyestradiol
• 4-hydroxyestradiol
• Catechol O-Methyltransferase
• Vitamin B 12

Topics

• Anticarcinogenic Agents (pharmacology, therapeutic use)
• Breast Neoplasms (epidemiology, prevention & control)
• Catechol O-Methyltransferase (physiology)
• Catechol O-Methyltransferase Inhibitors
• Estradiol (analogs & derivatives, metabolism)
• Estrogens (toxicity)
• Estrogens, Catechol (metabolism)
• Female
• Folic Acid (pharmacology, therapeutic use)
• Humans
• Hyperhomocysteinemia (epidemiology)
• Kinetics
• Methylation (drug effects)
• Models, Biological
• Mutagenicity Tests
• Neoplasms, Experimental (chemically induced)
• Neoplasms, Hormone-Dependent (epidemiology, prevention & control)
• Risk Factors
• S-Adenosylhomocysteine (adverse effects, metabolism)
• Uterine Neoplasms (epidemiology, prevention & control)
• Vitamin B 12 (pharmacology, therapeutic use)
• Vitamin B 6 (pharmacology, therapeutic use)