Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation

Anders Mälarstig (), Felix Grassmann, Leo Dahl, Marios Dimitriou, Dianna McLeod, Marike Gabrielson, Karl Smith-Byrne, Cecilia E. Thomas, Tzu-Hsuan Huang, Simon K. G. Forsberg, Per Eriksson, Mikael Ulfstedt, Mattias Johansson, Aleksandr V. Sokolov, Helgi B. Schiöth, Per Hall, Jochen M. Schwenk, Kamila Czene and Åsa K. Hedman
Additional contact information
Anders Mälarstig: Karolinska Institutet
Felix Grassmann: Karolinska Institutet
Leo Dahl: KTH Royal Institute of Technology
Marios Dimitriou: Karolinska Institutet
Dianna McLeod: Karolinska Institutet
Marike Gabrielson: Karolinska Institutet
Karl Smith-Byrne: University of Oxford
Cecilia E. Thomas: KTH Royal Institute of Technology
Tzu-Hsuan Huang: Cancer Immunology Discovery, Pfizer Inc.
Simon K. G. Forsberg: Olink Proteomics AB
Per Eriksson: Olink Proteomics AB
Mikael Ulfstedt: Olink Proteomics AB
Mattias Johansson: Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO)
Aleksandr V. Sokolov: Uppsala University
Helgi B. Schiöth: Uppsala University
Per Hall: Karolinska Institutet
Jochen M. Schwenk: KTH Royal Institute of Technology
Kamila Czene: Karolinska Institutet
Åsa K. Hedman: Karolinska Institutet

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: Abstract Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.

Date: 2023
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DOI: 10.1038/s41467-023-43485-8

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