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Identifying therape...
Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
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- Smith-Byrne, Karl (author)
- Univ Oxford, Canc Epidemiol Unit, Oxford Populat Hlth, Oxford, England.
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- Hedman, Åsa (author)
- Pfizer Worldwide Res Dev & Med, External Sci & Innovat, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.
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- Dimitriou, Marios (author)
- Karolinska Institutet,Pfizer Worldwide Res Dev & Med, External Sci & Innovat, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.
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- Desai, Trishna (author)
- Univ Oxford, Canc Epidemiol Unit, Oxford Populat Hlth, Oxford, England.
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- Sokolov, Aleksandr V. (author)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
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- Schiöth, Helgi B. (author)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
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- Koprulu, Mine (author)
- Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.
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- Pietzner, Maik (author)
- Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.;Charite Univ Medizin Berlin, Berlin Inst Hlth, Computat Med, Berlin, Germany.;Queen Mary Univ London, Precis Healthcare Inst, London, England.
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- Langenberg, Claudia (author)
- Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.;Charite Univ Medizin Berlin, Berlin Inst Hlth, Computat Med, Berlin, Germany.;Queen Mary Univ London, Precis Healthcare Inst, London, England.
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- Atkins, Joshua (author)
- Univ Oxford, Canc Epidemiol Unit, Oxford Populat Hlth, Oxford, England.
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- Cortez Penha, Ricardo (author)
- Int Agcy Res Canc IARC WHO, Genom Epidemiol Branch, Lyon, France.
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- McKay, James (author)
- Int Agcy Res Canc IARC WHO, Genom Epidemiol Branch, Lyon, France.
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- Brennan, Paul (author)
- Int Agcy Res Canc IARC WHO, Genom Epidemiol Branch, Lyon, France.
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- Zhou, Sirui (author)
- McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
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- Richards, Brent J. (author)
- McGill Univ, Dept Med Endocrinol, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada.
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- Yarmolinsky, James (author)
- Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, England.
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- Martin, Richard M. (author)
- Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, England.;Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, England.;Univ Bristol, Hosp Bristol & Weston NHS Fdn Trust, NIHR Bristol Biomed Res Ctr, Bristol, England.
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- Borlido, Joana (author)
- Pfizer Inc, Canc Immunol Discovery, Pfizer Worldwide Res & Dev Med, San Diego, CA USA.
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- Mu, Xinmeng J. (author)
- Pfizer Inc, Oncol Res Unit, Pfizer Worldwide Res & Dev Med, San Diego, CA USA.
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- Butterworth, Adam (author)
- Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
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- Shen, Xia (author)
- Univ Edinburgh, Usher Inst, MRC Human Genet Unit, Edinburgh, Scotland.
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- Wilson, Jim (author)
- Univ Edinburgh, Usher Inst, MRC Human Genet Unit, Edinburgh, Scotland.
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- Assimes, Themistocles L. (author)
- Stanford Univ, Div Cardiovasc Med, Stanford, CA USA.;Stanford Univ, Cardiovasc Inst, Sch Med, Stanford, CA USA.
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- Hung, Rayjean J. (author)
- Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON, Canada.;Univ Toronto, Toronto, ON, Canada.
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- Amos, Christopher (author)
- Baylor Med Coll, Inst Clin & Translat Res, Dept Med, Epidemiol Sect, Houston, TX USA.
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- Purdue, Mark (author)
- NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
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- Rothman, Nathaniel (author)
- NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Rockville, MD USA.
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- Chanock, Stephen (author)
- NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
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- Travis, Ruth C. (author)
- Univ Oxford, Canc Epidemiol Unit, Oxford Populat Hlth, Oxford, England.
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- Johansson, Mattias (author)
- Int Agcy Res Canc IARC WHO, Genom Epidemiol Branch, Lyon, France.
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- Mälarstig, Anders (author)
- Pfizer Worldwide Res Dev & Med, External Sci & Innovat, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.
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Univ Oxford, Canc Epidemiol Unit, Oxford Populat Hlth, Oxford, England Pfizer Worldwide Res Dev & Med, External Sci & Innovat, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden. (creator_code:org_t)
- Springer Nature, 2024
- 2024
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
- Related links:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Smith-Byrne, Kar ...
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Hedman, Åsa
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Dimitriou, Mario ...
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Desai, Trishna
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Sokolov, Aleksan ...
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Schiöth, Helgi B ...
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show more...
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Koprulu, Mine
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Pietzner, Maik
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Langenberg, Clau ...
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Atkins, Joshua
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Cortez Penha, Ri ...
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McKay, James
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Brennan, Paul
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Zhou, Sirui
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Richards, Brent ...
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Yarmolinsky, Jam ...
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Martin, Richard ...
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Borlido, Joana
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Mu, Xinmeng J.
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Butterworth, Ada ...
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Shen, Xia
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Wilson, Jim
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Assimes, Themist ...
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Hung, Rayjean J.
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Amos, Christophe ...
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Purdue, Mark
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Rothman, Nathani ...
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Chanock, Stephen
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Travis, Ruth C.
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Johansson, Matti ...
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Mälarstig, Ander ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Nature Communica ...
- By the university
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Uppsala University
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Karolinska Institutet