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Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation

Author

Listed:
  • Anders Mälarstig

    (Karolinska Institutet
    Pfizer Worldwide Research Development and Medical)

  • Felix Grassmann

    (Karolinska Institutet
    Health and Medical University)

  • Leo Dahl

    (KTH Royal Institute of Technology)

  • Marios Dimitriou

    (Karolinska Institutet
    Pfizer Worldwide Research Development and Medical)

  • 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
    Södersjukhuset)

  • Jochen M. Schwenk

    (KTH Royal Institute of Technology)

  • Kamila Czene

    (Karolinska Institutet)

  • Åsa K. Hedman

    (Karolinska Institutet
    Pfizer Worldwide Research Development and Medical)

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.

Suggested Citation

  • 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 & Mi, 2023. "Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43485-8
    DOI: 10.1038/s41467-023-43485-8
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    References listed on IDEAS

    as
    1. Stefan Enroth & Åsa Johansson & Sofia Bosdotter Enroth & Ulf Gyllensten, 2014. "Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    2. Kyriaki Michailidou & Sara Lindström & Joe Dennis & Jonathan Beesley & Shirley Hui & Siddhartha Kar & Audrey Lemaçon & Penny Soucy & Dylan Glubb & Asha Rostamianfar & Manjeet K. Bolla & Qin Wang & Jon, 2017. "Association analysis identifies 65 new breast cancer risk loci," Nature, Nature, vol. 551(7678), pages 92-94, November.
    3. Amand F. Schmidt & Chris Finan & Maria Gordillo-Marañón & Folkert W. Asselbergs & Daniel F. Freitag & Riyaz S. Patel & Benoît Tyl & Sandesh Chopade & Rupert Faraway & Magdalena Zwierzyna & Aroon D. Hi, 2020. "Genetic drug target validation using Mendelian randomisation," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    4. Samir M. Hanash & Sharon J. Pitteri & Vitor M. Faca, 2008. "Mining the plasma proteome for cancer biomarkers," Nature, Nature, vol. 452(7187), pages 571-579, April.
    5. Maik Pietzner & Eleanor Wheeler & Julia Carrasco-Zanini & Nicola D. Kerrison & Erin Oerton & Mine Koprulu & Jian’an Luan & Aroon D. Hingorani & Steve A. Williams & Nicholas J. Wareham & Claudia Langen, 2021. "Synergistic insights into human health from aptamer- and antibody-based proteomic profiling," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    6. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 615(7952), pages 19-19, March.
    7. Michal Zimmermann & Olga Murina & Martin A. M. Reijns & Angelo Agathanggelou & Rachel Challis & Žygimantė Tarnauskaitė & Morwenna Muir & Adeline Fluteau & Michael Aregger & Andrea McEwan & Wei Yuan & , 2018. "CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions," Nature, Nature, vol. 559(7713), pages 285-289, July.
    8. Benjamin B. Sun & Joseph C. Maranville & James E. Peters & David Stacey & James R. Staley & James Blackshaw & Stephen Burgess & Tao Jiang & Ellie Paige & Praveen Surendran & Clare Oliver-Williams & Mi, 2018. "Genomic atlas of the human plasma proteome," Nature, Nature, vol. 558(7708), pages 73-79, June.
    9. Gibran Hemani & Kate Tilling & George Davey Smith, 2017. "Orienting the causal relationship between imprecisely measured traits using GWAS summary data," PLOS Genetics, Public Library of Science, vol. 13(11), pages 1-22, November.
    10. Benjamin B. Sun & Joshua Chiou & Matthew Traylor & Christian Benner & Yi-Hsiang Hsu & Tom G. Richardson & Praveen Surendran & Anubha Mahajan & Chloe Robins & Steven G. Vasquez-Grinnell & Liping Hou & , 2023. "Plasma proteomic associations with genetics and health in the UK Biobank," Nature, Nature, vol. 622(7982), pages 329-338, October.
    11. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
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