Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers

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...

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Autori principali: Smith-Byrne, K, Hedman, Å, Dimitriou, M, Desai, T, Sokolov, AV, Schioth, HB, Koprulu, M, Pietzner, M, Langenberg, C, Atkins, J, Penha, RC, McKay, J, Brennan, P, Zhou, S, Richards, BJ, Yarmolinsky, J, Martin, RM, Borlido, J, Mu, XJ, Butterworth, A, Shen, X, Wilson, J, Assimes, TL, Hung, RJ, Travis, RC
Natura: Journal article
Lingua:English
Pubblicazione: Nature Research 2024
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author Smith-Byrne, K
Hedman, Å
Dimitriou, M
Desai, T
Sokolov, AV
Schioth, HB
Koprulu, M
Pietzner, M
Langenberg, C
Atkins, J
Penha, RC
McKay, J
Brennan, P
Zhou, S
Richards, BJ
Yarmolinsky, J
Martin, RM
Borlido, J
Mu, XJ
Butterworth, A
Shen, X
Wilson, J
Assimes, TL
Hung, RJ
Travis, RC
author_facet Smith-Byrne, K
Hedman, Å
Dimitriou, M
Desai, T
Sokolov, AV
Schioth, HB
Koprulu, M
Pietzner, M
Langenberg, C
Atkins, J
Penha, RC
McKay, J
Brennan, P
Zhou, S
Richards, BJ
Yarmolinsky, J
Martin, RM
Borlido, J
Mu, XJ
Butterworth, A
Shen, X
Wilson, J
Assimes, TL
Hung, RJ
Travis, RC
author_sort Smith-Byrne, K
collection OXFORD
description 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.
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spelling oxford-uuid:f100efb4-9804-435e-ac3e-c45cbb9bff1c2024-07-20T14:59:00ZIdentifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f100efb4-9804-435e-ac3e-c45cbb9bff1cEnglishJisc Publications RouterNature Research2024Smith-Byrne, KHedman, ÅDimitriou, MDesai, TSokolov, AVSchioth, HBKoprulu, MPietzner, MLangenberg, CAtkins, JPenha, RCMcKay, JBrennan, PZhou, SRichards, BJYarmolinsky, JMartin, RMBorlido, JMu, XJButterworth, AShen, XWilson, JAssimes, TLHung, RJTravis, RCCirculating 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.
spellingShingle Smith-Byrne, K
Hedman, Å
Dimitriou, M
Desai, T
Sokolov, AV
Schioth, HB
Koprulu, M
Pietzner, M
Langenberg, C
Atkins, J
Penha, RC
McKay, J
Brennan, P
Zhou, S
Richards, BJ
Yarmolinsky, J
Martin, RM
Borlido, J
Mu, XJ
Butterworth, A
Shen, X
Wilson, J
Assimes, TL
Hung, RJ
Travis, RC
Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
title Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
title_full Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
title_fullStr Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
title_full_unstemmed Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
title_short Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
title_sort identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
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