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Evaluation of assoc...
Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk
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- Shu, Xiang (author)
- Vanderbilt University
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- Bao, Jiandong (author)
- Vanderbilt University
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- Wu, Lang (author)
- Vanderbilt University
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- Long, Jirong (author)
- Vanderbilt University
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- Shu, Xiao Ou (author)
- Vanderbilt University
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- Guo, Xingyi (author)
- Vanderbilt University
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- Yang, Yaohua (author)
- Vanderbilt University
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- Michailidou, Kyriaki (author)
- University of Cambridge,Cyprus Institute of Neurology and Genetics
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- Bolla, Manjeet K. (author)
- University of Cambridge
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- Wang, Qin (author)
- University of Cambridge
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- Dennis, Joe (author)
- University of Cambridge
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- Andrulis, Irene L. (author)
- University of Toronto,Mount Sinai Hospital of University of Toronto
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Castelao, Jose E. (author)
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- Dörk, Thilo (author)
- Hannover Medical School
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- Gago-Dominguez, Manuela (author)
- University of California, San Diego,Complejo Hospitalario Universitario de Santiago
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- García-Closas, Montserrat (author)
- National Cancer Institute, USA
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- Giles, Graham G. (author)
- Cancer Council Victoria
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- Lophatananon, Artitaya (author)
- University of Warwick,University of Manchester
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- Muir, Kenneth (author)
- University of Warwick,University of Manchester
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- Olsson, Håkan (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Rennert, Gadi (author)
- Technion - Israel Institute of Technology
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- Saloustros, Emmanouil (author)
- University Hospital of Heraklion
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- Scott, Rodney J. (author)
- John Hunter Hospital
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- Southey, Melissa C. (author)
- University of Melbourne
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- Pharoah, Paul D.P. (author)
- University of Cambridge
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- Milne, Roger L. (author)
- Cancer Council Victoria
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- Kraft, Peter (author)
- Harvard University
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- Simard, Jacques (author)
- Centre hospitalier universitaire de Québec
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- Easton, Douglas F. (author)
- University of Cambridge
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- Zheng, Wei (author)
- Vanderbilt University
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(creator_code:org_t)
- 2019-07-16
- 2020
- English 9 s.
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:8, s. 2130-2138
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http://dx.doi.org/10...
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Abstract
Subject headings
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- A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancer via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82–1.18, p values: 6.96 × 10−4–3.28 × 10−8), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- breast cancer
- circulating protein biomarkers
- genetics
- instruments
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Shu, Xiang
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Bao, Jiandong
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Wu, Lang
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Long, Jirong
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Shu, Xiao Ou
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Guo, Xingyi
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show more...
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Yang, Yaohua
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Michailidou, Kyr ...
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Bolla, Manjeet K ...
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Wang, Qin
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Dennis, Joe
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Andrulis, Irene ...
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Castelao, Jose E ...
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Dörk, Thilo
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Gago-Dominguez, ...
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García-Closas, M ...
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Giles, Graham G.
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Lophatananon, Ar ...
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Muir, Kenneth
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Olsson, Håkan
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Rennert, Gadi
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Saloustros, Emma ...
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Scott, Rodney J.
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Southey, Melissa ...
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Pharoah, Paul D. ...
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Milne, Roger L.
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Kraft, Peter
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Simard, Jacques
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Easton, Douglas ...
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Zheng, Wei
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- MEDICAL AND HEALTH SCIENCES
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Lund University