| Title |
SLCO1B1 polymorphisms and plasma estrone conjugates in postmenopausal women with ER+ breast cancer: genome-wide association studies of the estrone pathway
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, April 2017
|
| DOI | 10.1007/s10549-017-4243-3 |
| Pubmed ID | |
| Authors |
Tanda M. Dudenkov, James N. Ingle, Aman U. Buzdar, Mark E. Robson, Michiaki Kubo, Irada Ibrahim-zada, Anthony Batzler, Gregory D. Jenkins, Tracy L. Pietrzak, Erin E. Carlson, Poulami Barman, Matthew P. Goetz, Donald W. Northfelt, Alvaro Moreno-Aspita, Clark V. Williard, Krishna R. Kalari, Yusuke Nakamura, Liewei Wang, Richard M. Weinshilboum |
| Abstract |
Estrone (E1), the major circulating estrogen in postmenopausal women, promotes estrogen-receptor positive (ER+) breast tumor growth and proliferation. Two major reactions contribute to E1 plasma concentrations, aromatase (CYP19A1) catalyzed E1 synthesis from androstenedione and steroid sulfatase (STS) catalyzed hydrolysis of estrone conjugates (E1Cs). E1Cs have been associated with breast cancer risk and may contribute to tumor progression since STS is expressed in breast cancer where its activity exceeds that of aromatase. We performed genome-wide association studies (GWAS) to identify SNPs associated with variation in plasma concentrations of E1Cs, E1, and androstenedione in 774 postmenopausal women with resected early-stage ER+ breast cancer. Hormone concentrations were measured prior to aromatase inhibitor therapy. Multiple SNPs in SLCO1B1, a gene encoding a hepatic influx transporter, displayed genome-wide significant associations with E1C plasma concentrations and with the E1C/E1 ratio. The top SNP for E1C concentrations, rs4149056 (p = 3.74E-11), was a missense variant that results in reduced transporter activity. Patients homozygous for the variant allele had significantly higher average E1C plasma concentrations than did other patients. Furthermore, three other SLCO1B1 SNPs, not in LD with rs4149056, were associated with both E1C concentrations and the E1C/E1 ratio and were cis-eQTLs for SLCO1B3. GWAS signals of suggestive significance were also observed for E1, androstenedione, and the E1/androstenedione ratio. These results suggest a mechanism for genetic variation in E1C plasma concentrations as well as possible SNP biomarkers to identify ER+ breast cancer patients for whom STS inhibitors might be of clinical value. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 30 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 20% |
| Student > Ph. D. Student | 4 | 13% |
| Researcher | 4 | 13% |
| Other | 3 | 10% |
| Student > Master | 2 | 7% |
| Other | 2 | 7% |
| Unknown | 9 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 20% |
| Biochemistry, Genetics and Molecular Biology | 4 | 13% |
| Medicine and Dentistry | 4 | 13% |
| Mathematics | 1 | 3% |
| Agricultural and Biological Sciences | 1 | 3% |
| Other | 3 | 10% |
| Unknown | 11 | 37% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 December 2023.
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#19,942,460
of 25,382,035 outputs
Outputs from Breast Cancer Research and Treatment
#3,860
of 4,972 outputs
Outputs of similar age
#225,009
of 309,665 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#68
of 108 outputs
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