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
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
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/).