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Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk
Author(s) -
Shu Xiang,
Bao Jiandong,
Wu Lang,
Long Jirong,
Shu XiaoOu,
Guo Xingyi,
Yang Yaohua,
Michailidou Kyriaki,
Bolla Manjeet K.,
Wang Qin,
Dennis Joe,
Andrulis Irene L.,
Castelao Jose E.,
Dörk Thilo,
GagoDominguez Manuela,
GarcíaClosas Montserrat,
Giles Graham G.,
Lophatana Artitaya,
Muir Kenneth,
Olsson Håkan,
Rennert Gadi,
Saloustros Emmanouil,
Scott Rodney J.,
Southey Melissa C.,
Pharoah Paul D.P.,
Milne Roger L.,
Kraft Peter,
Simard Jacques,
Easton Douglas F.,
Zheng Wei
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32542
Subject(s) - breast cancer , estrogen receptor , biology , cancer , oncology , quantitative proteomics , proteomics , medicine , bioinformatics , genetics , gene
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.