Identifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank

Keren Papier (), Joshua R. Atkins, Tammy Y. N. Tong, Kezia Gaitskell, Trishna Desai, Chibuzor F. Ogamba, Mahboubeh Parsaeian, Gillian K. Reeves, Ian G. Mills, Tim J. Key, Karl Smith-Byrne and Ruth C. Travis
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Keren Papier: University of Oxford
Joshua R. Atkins: University of Oxford
Tammy Y. N. Tong: University of Oxford
Kezia Gaitskell: University of Oxford
Trishna Desai: University of Oxford
Chibuzor F. Ogamba: University of Oxford
Mahboubeh Parsaeian: University of Oxford
Gillian K. Reeves: University of Oxford
Ian G. Mills: University of Oxford
Tim J. Key: University of Oxford
Karl Smith-Byrne: University of Oxford
Ruth C. Travis: University of Oxford

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract The availability of protein measurements and whole exome sequence data in the UK Biobank enables investigation of potential observational and genetic protein-cancer risk associations. We investigated associations of 1463 plasma proteins with incidence of 19 cancers and 9 cancer subsites in UK Biobank participants (average 12 years follow-up). Emerging protein-cancer associations were further explored using two genetic approaches, cis-pQTL and exome-wide protein genetic scores (exGS). We identify 618 protein-cancer associations, of which 107 persist for cases diagnosed more than seven years after blood draw, 29 of 618 were associated in genetic analyses, and four had support from long time-to-diagnosis ( > 7 years) and both cis-pQTL and exGS analyses: CD74 and TNFRSF1B with NHL, ADAM8 with leukemia, and SFTPA2 with lung cancer. We present multiple blood protein-cancer risk associations, including many detectable more than seven years before cancer diagnosis and that had concordant evidence from genetic analyses, suggesting a possible role in cancer development.

Date: 2024
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DOI: 10.1038/s41467-024-48017-6

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