Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk.
Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols. In a case-control study, we evaluated the association of the low-activity allele (COMT(Met)) with breast cancer risk. Compared to women with COMT(Val/Val), COMT(Met/Met) was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The association of risk with at least one low-activity COMT(Met) allele was strongest among the heaviest premenopausal women (OR, 5.7; CI, 1.1-30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.
Thompson
P A
PA
Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas 72205, USA.
Shields
P G
PG
Freudenheim
J L
JL
Stone
A
A
Vena
J E
JE
Marshall
J R
JR
Graham
S
S
Laughlin
R
R
Nemoto
T
T
Kadlubar
F F
FF
Ambrosone
C B
CB
D015992:Body Mass Index; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D018570:Risk Assessment
D009363:Neoplasm Proteins; D002394:Catechol O-Methyltransferase