TY - JOUR
T1 - Catechol-O-methyltransferase
T2 - Characteristics, polymorphisms and role in breast cancer
AU - Yager, James D.
PY - 2012/6
Y1 - 2012/6
N2 - Catechol estrogens are carcinogenic, probably because of their estrogenicity and potential for further oxidative metabolism to reactive quinones. Estrogenic quinones cause oxidative DNA damage as well as form mutagenic depurinating adenine and guanine adducts. O-Methylation by catechol-O-methyltransferase (COMT) blocks their estrogenicity and prevents their oxidation to quinones. A single gene encodes both membrane bound (MB) and soluble (S) forms of COMT. The COMT gene contains 34 single nucleotide polymorphisms (SNPs). The valine108 (S-COMT)/158 (MB-COMT) SNP encodes a low activity form of COMT and has been widely studied as a putative risk factor for breast cancer, with inconsistent results. Investigations of two other SNPs in the promoter of MB-COMT that may affect its expression have also provided mixed results. Future studies on the role of COMT in breast cancer should incorporate measurement of biomarkers that reflect COMT activity and its protective effects.
AB - Catechol estrogens are carcinogenic, probably because of their estrogenicity and potential for further oxidative metabolism to reactive quinones. Estrogenic quinones cause oxidative DNA damage as well as form mutagenic depurinating adenine and guanine adducts. O-Methylation by catechol-O-methyltransferase (COMT) blocks their estrogenicity and prevents their oxidation to quinones. A single gene encodes both membrane bound (MB) and soluble (S) forms of COMT. The COMT gene contains 34 single nucleotide polymorphisms (SNPs). The valine108 (S-COMT)/158 (MB-COMT) SNP encodes a low activity form of COMT and has been widely studied as a putative risk factor for breast cancer, with inconsistent results. Investigations of two other SNPs in the promoter of MB-COMT that may affect its expression have also provided mixed results. Future studies on the role of COMT in breast cancer should incorporate measurement of biomarkers that reflect COMT activity and its protective effects.
UR - http://www.scopus.com/inward/record.url?scp=84875225571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875225571&partnerID=8YFLogxK
U2 - 10.1016/j.ddmec.2012.10.002
DO - 10.1016/j.ddmec.2012.10.002
M3 - Review article
C2 - 23734165
AN - SCOPUS:84875225571
SN - 1740-6765
VL - 9
SP - e41-e46
JO - Drug Discovery Today: Disease Mechanisms
JF - Drug Discovery Today: Disease Mechanisms
IS - 1-2
ER -