J Cancer 2020; 11(16):4652-4661. doi:10.7150/jca.42669

Review

CYP1B1 gene: Implications in glaucoma and cancer

Arwa Alsubait2, Wadha Aldossary1, Mamoon Rashid2, Amani Algamdi1, Bahauddeen M. Alrfaei2✉

1. Biochemisty, King Saud University, Saudi Arabia.
2. King Abdullah International Medical Research Center (KAIMRC)/ King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), MNGHA, Saudi Arabia.
✉ Corresponding author: Dr. Bahauddeen Alrfaei, E-mail: alrfaeiba@ngha.med.sa., Cellular Therapy and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC)/ King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard - Health Affairs, Saudi Arabia. P.O. Box 22490, Riyadh 11426 MailCode 1515.

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Citation:
Alsubait A, Aldossary W, Rashid M, Algamdi A, Alrfaei BM. CYP1B1 gene: Implications in glaucoma and cancer. J Cancer 2020; 11(16):4652-4661. doi:10.7150/jca.42669. Available from http://www.jcancer.org/v11p4652.htm

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Abstract

Glaucoma is a serious disease that can lead to irreversible loss of vision. Patients with primary congenital glaucoma may have elevated intraocular pressure. Hypertension causes damages to intraocular structures and affects the Schlemm's canal, collector channels, trabecular meshwork, and optic nerve's molecular structures. An important gene that is defective in patients with glaucoma is CYP1B1, a gene associated with optic nerve deterioration. CYP1B1is a key enzyme involved in the metabolism of exogenous and endogenous compounds. Also, it is critical in the detoxification of pre-carcinogens, such as polycyclic aromatic hydrocarbons and estrogen. It catalyzes their conversion into metabolites subsequently eliminated from the body. In malignant tumors, the CYP1B1 promoter is hypomethylated. CYP1B1 overexpression results in the conversion of estrogens to quinone forms, which bind with DNA and create a predisposition for cancer in several organs, such as the brain, breast, and ovary. Increased cytokine interleukin-6 and leptin lead to elevated CYP1B1 activity, which possibly causes cancer. In addition, the expression of aromatic hydrocarbon receptors is increased in tumor tissues, and it elevates oxidative stress and cell growth. TCGA database analysis showed increased survival at bladder and renal carcinoma when CYP1B1 expression is low. Therefore, alteration of CYP1B1 expression may suggest a therapeutic benefit for multiple diseases such as glaucoma and cancer.

Keywords: Glaucoma, CYP1B1, cancer, optic nerve, carcinogens, estrogens