Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.

Authors

• James Yarmolinsky, University of BristolFollow
• Jamie W. Robinson, University of Bristol
• Daniela Mariosa, International Agency for Research on Cancer, Lyon, France
• Ville Karhunen, University of Oulu
• Jian Huang, Imperial College London
• Niki Dimou, International Agency for Research on Cancer, Lyon, France
• Neil Murphy, International Agency for Research on Cancer, Lyon, France
• Kimberley Burrows, University of Bristol
• Emmanouil Bouras, University of Ioannina
• Karl Smith-Byrne, University of Oxford
• Sarah J. Lewis, University of Bristol
• Tessel E. Galesloot, Radboud University Medical Center
• Lambertus A. Kiemeney, Radboud University Medical Center
• Sita Vermeulen, Radboud University Medical Center
• Paul Martin, University of Bristol
• Demetrius Albanes, National Institutes of Health
• Lifang Hou, Northwestern University Feinberg School of Medicine
• Polly A. Newcomb, Fred Hutchinson Cancer Research Center
• Emily White, Fred Hutchinson Cancer Research Center
• Alicja Wolk, Karolinska Institutet
• Anna H. Wu, University of Southern California
• Loïc Le Marchand, University of Hawaii Cancer Center
• Amanda I. Phipps, Fred Hutchinson Cancer Research Center
• Daniel D. Buchanan, University of Melbourne
• The International Lung Cancer Consortium
• The PRACTICAL Consortium
• Sizheng Steven Zhao, University of Manchester
• Dipender Gill, Imperial College London
• Stephen J. Chanock, National Institutes of Health
• Mark P. Purdue, National Institutes of Health
• George Davey Smith, University of Bristol
• Paul Brennan, International Agency for Research on Cancer, Lyon, France
• Karl-Heinz Herzig, University of Oulu
• Marjo-Riitta Järvelin, International Agency for Research on Cancer, Lyon, France
• Chris I. Amos, Baylor College of Medicine
• Rayjean J. Hung, Sinai Health, Toronto, Canada
• Abbas Dehghan, Imperial College London
• Mattias Johansson, International Agency for Research on Cancer, Lyon, France
• Marc J. Gunter, Imperial College London
• Kostas K. Tsilidis, Imperial College London
• Richard M. Martin, University of Bristol

Abstract

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10

FINDINGS: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH

INTERPRETATION: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated.

Document Type

Article

Publication Date

2-1-2024

Notes/Citation Information

© 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.ebiom.2024.104991

Funding Information

Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654).

Repository Citation

Yarmolinsky, James; Robinson, Jamie W.; Mariosa, Daniela; Karhunen, Ville; Huang, Jian; Dimou, Niki; Murphy, Neil; Burrows, Kimberley; Bouras, Emmanouil; Smith-Byrne, Karl; Lewis, Sarah J.; Galesloot, Tessel E.; Kiemeney, Lambertus A.; Vermeulen, Sita; Martin, Paul; Albanes, Demetrius; Hou, Lifang; Newcomb, Polly A.; White, Emily; Wolk, Alicja; Wu, Anna H.; Le Marchand, Loïc; Phipps, Amanda I.; Buchanan, Daniel D.; The International Lung Cancer Consortium; The PRACTICAL Consortium; Zhao, Sizheng Steven; Gill, Dipender; Chanock, Stephen J.; Purdue, Mark P.; Davey Smith, George; Brennan, Paul; Herzig, Karl-Heinz; Järvelin, Marjo-Riitta; Amos, Chris I.; Hung, Rayjean J.; Dehghan, Abbas; Johansson, Mattias; Gunter, Marc J.; Tsilidis, Kostas K.; and Martin, Richard M., "Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis." (2024). Markey Cancer Center Faculty Publications. 433.
https://uknowledge.uky.edu/markey_facpub/433