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, Ruth C Travis

Research output: Contribution to journalArticlepeer-review

18 Downloads (Pure)

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.

Original languageEnglish
Article number4010
Number of pages12
JournalNature Communications
Volume15
DOIs
Publication statusPublished - 15 May 2024

Bibliographical note

© 2024. The Author(s).

Keywords

  • Humans
  • United Kingdom/epidemiology
  • Neoplasms/genetics
  • Risk Factors
  • Biological Specimen Banks
  • Male
  • Female
  • Exome/genetics
  • Proteomics
  • Prospective Studies
  • Middle Aged
  • Blood Proteins/genetics
  • Aged
  • Exome Sequencing
  • Genetic Predisposition to Disease
  • Incidence
  • UK Biobank

Fingerprint

Dive into the research topics of 'Identifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank'. Together they form a unique fingerprint.

Cite this