Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Xiang Shu
  • Jiandong Bao
  • Lang Wu
  • Jirong Long
  • Xiao Ou Shu
  • Xingyi Guo
  • Yaohua Yang
  • Kyriaki Michailidou
  • Manjeet K. Bolla
  • Qin Wang
  • Joe Dennis
  • Irene L. Andrulis
  • Jose E. Castelao
  • Thilo Dörk
  • Manuela Gago-Dominguez
  • Montserrat García-Closas
  • Graham G. Giles
  • Artitaya Lophatananon
  • Kenneth Muir
  • Gadi Rennert
  • Emmanouil Saloustros
  • Rodney J. Scott
  • Melissa C. Southey
  • Paul D.P. Pharoah
  • Roger L. Milne
  • Peter Kraft
  • Jacques Simard
  • Douglas F. Easton
  • Wei Zheng
Enheter & grupper
Externa organisationer
  • Vanderbilt University School of Medicine
  • University of Cambridge
  • Cyprus Institute of Neurology and Genetics
  • Mount Sinai Hospital of University of Toronto
  • University of Toronto
  • Hannover Medical School
  • Complejo Hospitalario Universitario de Santiago
  • University of California, San Diego
  • National Cancer Institute
  • Cancer Council Victoria
  • University of Warwick
  • University of Manchester
  • Technion - Israel Institute of Technology
  • University Hospital of Heraklion
  • John Hunter Hospital
  • University of Melbourne
  • Harvard University
  • Centre hospitalier universitaire de Québec
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi

Nyckelord

Originalspråkengelska
TidskriftInternational Journal of Cancer
StatusE-pub ahead of print - 2019
PublikationskategoriForskning
Peer review utfördJa