Association of Catechol-O-methyltransferase polymorphism Val158Met and mammographic density: A meta-analysis

• Published in: Gene Vol. 624; pp. 34 - 42
• Main Authors: Kallionpää, Roope A., Uusitalo, Elina, Peltonen, Juha
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-08-2017
• Subjects: Adult; Aged; Breast Density - genetics; Catechol O-Methyltransferase - genetics; Catechol-O-methyltransferase; Female; Hormone replacement therapy; Hormone Replacement Therapy - adverse effects; Humans; Mammographic density; Mammography; Menopause; Methylation; Middle Aged; Polymorphism, Single Nucleotide; CC; Val; Catechol-O-methyltransferase; NR; CI; Menopause; ICC; BI-RADS; HRT; PCR-RFLP; COMT; PCR-MS; MLO; SD; Mammographic density; HWE; MD; Hormone replacement therapy; Methylation; Met; BMI
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2017.04.049

The Val158Met polymorphism in catechol-O-methyltransferase (COMT) enzyme reduces the methylation of catechol estrogens, which may affect mammographic density. High mammographic density is a known risk factor of breast cancer. Our aim was to perform meta-analysis of the effect of COMT Val158Met polymorphism on mammographic density.
Original studies reporting data on mammographic density, stratified by the presence of COMT Val158Met polymorphism, were identified and combined using genetic models Met/Val vs. Val/Val, Met/Met vs. Val/Val, Val/Met+Met/Met vs. Val/Val (dominant model) and Met/Met vs. Val/Met+Val/Val (recessive model). Subgroup analyses by breast cancer status, menopausal status and use of hormone replacement therapy (HRT) were also performed.
Eight studies were included in the meta-analysis. The overall effect in percent mammographic density was −1.41 (CI −2.86 to 0.05; P=0.06) in the recessive model. Exclusion of breast cancer patients increased the effect size to −1.93 (CI −3.49 to −0.37; P=0.02). The results suggested opposite effect of COMT Val158Met for postmenopausal users of HRT versus premenopausal women or postmenopausal non-users of HRT.
COMT Val158Met polymorphism may be associated with mammographic density at least in healthy women. Menopausal status and HRT should be taken into account in future studies to avoid masking of the underlying effects.
•Association of COMT Val158Met polymorphism and mammographic density was studied.•A borderline significant decrease in density was found in Met/Met genotype.•Exclusion of breast cancer patients increased the effect size.•The effect may be modified by menopausal status and hormone replacement therapy.•Future studies should stratify analyses by these factors.