Author
Listed:
- Karl Smith-Byrne
(University of Oxford)
- Åsa Hedman
(Development and Medical
Karolinska Institute)
- Marios Dimitriou
(Development and Medical
Karolinska Institute)
- Trishna Desai
(University of Oxford)
- Alexandr V. Sokolov
(Uppsala University)
- Helgi B. Schioth
(Uppsala University)
- Mine Koprulu
(University of Cambridge)
- Maik Pietzner
(University of Cambridge
Berlin Institute of Health at Charité – Universitätsmedizin Berlin
Queen Mary University of London)
- Claudia Langenberg
(University of Cambridge
Berlin Institute of Health at Charité – Universitätsmedizin Berlin
Queen Mary University of London)
- Joshua Atkins
(University of Oxford)
- Ricardo Cortez Penha
(International Agency for Research on Cancer (IARC-WHO))
- James McKay
(International Agency for Research on Cancer (IARC-WHO))
- Paul Brennan
(International Agency for Research on Cancer (IARC-WHO))
- Sirui Zhou
(McGill University)
- Brent J. Richards
(McGill University)
- James Yarmolinsky
(University of Bristol)
- Richard M. Martin
(University of Bristol
University of Bristol
Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol)
- Joana Borlido
(Pfizer Inc)
- Xinmeng J. Mu
(Pfizer Inc)
- Adam Butterworth
(University of Cambridge)
- Xia Shen
(University of Edinburgh)
- Jim Wilson
(University of Edinburgh)
- Themistocles L. Assimes
(Stanford University)
- Rayjean J. Hung
(Sinai Health System and University of Toronto)
- Christopher Amos
(Baylor Medical College)
- Mark Purdue
(National Cancer Institute)
- Nathaniel Rothman
(National Cancer Institute)
- Stephen Chanock
(National Cancer Institute)
- Ruth C. Travis
(University of Oxford)
- Mattias Johansson
(International Agency for Research on Cancer (IARC-WHO))
- Anders Mälarstig
(Development and Medical
Karolinska Institute)
Abstract
Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.
Suggested Citation
Karl Smith-Byrne & Åsa Hedman & Marios Dimitriou & Trishna Desai & Alexandr V. Sokolov & Helgi B. Schioth & Mine Koprulu & Maik Pietzner & Claudia Langenberg & Joshua Atkins & Ricardo Cortez Penha & J, 2024.
"Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers,"
Nature Communications, Nature, vol. 15(1), pages 1-11, December.
Handle:
RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46834-3
DOI: 10.1038/s41467-024-46834-3
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