Association of genetic polymorphisms with local steroid metabolism in human benign breasts | Polymorphisms and Breast Fluid Steroids Open Access (recommended)
Descriptions
- Resource type(s)
- Journal Article
- Keyword
- single nucleotide polymorphisms
steroid metabolizing enzymes
human breast
- Rights
- Attribution 4.0 International
- Creator
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Chatterton Jr, Robert Treat
Lee, Oukseub
Fought, Angela J
Shidfar, Ali
Heinz, Richard E
Kmiecik, Thomas E
Gann, Peter H
Khan, Seema Ahsan
- Abstract
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Purpose: Although alterations of concentrations in circulating steroids have been linked to single nucleotide polymorphisms (SNPs) of steroidogenic enzymes, we hypothesized that SNPs of such enzymes located within the breast affect local steroid concentrations more than products of such SNPs absorbed from the circulation.Methods: Steroids (estradiol, estrone, testosterone, androstenedione, DHEA, DHEA sulfate, progesterone) in nipple aspirate fluid (NAF) were purified by HPLC and they along with serum steroids were quantified by immunoassays. Polymorphisms of the transporter SLCO2B1 and enzymes HSD3B1, CYP19A1, HSD17B12, AKR1C3, CYP1B1, and SRD5A1 were measured in white blood cell DNA. Results: Steroid concentrations in NAF of subjects with homozygous minor genotypes differed from those with heterozygotes, i.e., SLCO2B1 (rs2851069) decreased DHEAS (p = 0.04), HSD17B12 (rs11555762) increased estradiol (p <0.004), and CYP1B1 (rs1056836) decreased estradiol (p = 0.017) and increased progesterone (p = 0.05). Also, in serum, CYP19A1 (rs10046 and rs700518) both decreased testosterone (p = 0.02) and SRD5A1 increased androstenedione (p=0.006). Steroids in subjects with major homozygotes did not differ from those with heterozygotes indicating recessive characteristics. Conclusions: In the breast, SNPs were associated with decreased uptake of DHEAS (SLCO2B1), increased estradiol concentrations through increased oxidoreductase activity (HSD17B12), or decreased estradiol concentrations by presumed formation of 4-hydroxyestradiol (CYP1B1). CYP19A1 was associated with decreased testosterone concentrations in serum but had no significant effect on estrogen or androgen concentrations within the breast. The hormone differences observed in NAF were not usually evident in serum, indicating the importance of assessing the effect of these SNPs within the breast.
- Related URL
- Publisher
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DigitalHub. Galter Health Sciences Library & Learning Center
- Date Created
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2021
- Language
- English
- Subject: MESH
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Breast
Polymorphism, Genetic
Enzymes
Steroids--metabolism
Nipple Aspirate Fluid
- Grants and funding
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This work was supported by the National Institutes of Health, National Cancer Institute, grant R01 CA 120555.
- DOI
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10.18131/g3-9f61-d833
File Details
- File Properties
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