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01-12-2022 | Lung Cancer | Research article

Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis

Authors: Emmanouil Bouras, Ville Karhunen, Dipender Gill, Jian Huang, Philip C. Haycock, Marc J. Gunter, Mattias Johansson, Paul Brennan, Tim Key, Sarah J. Lewis, Richard M. Martin, Neil Murphy, Elizabeth A. Platz, Ruth Travis, James Yarmolinsky, Verena Zuber, Paul Martin, Michail Katsoulis, Heinz Freisling, Therese Haugdahl Nøst, Matthias B. Schulze, Laure Dossus, Rayjean J. Hung, Christopher I. Amos, Ari Ahola-Olli, Saranya Palaniswamy, Minna Männikkö, Juha Auvinen, Karl-Heinz Herzig, Sirkka Keinänen-Kiukaanniemi, Terho Lehtimäki, Veikko Salomaa, Olli Raitakari, Marko Salmi, Sirpa Jalkanen, Marjo-Riitta Jarvelin, Abbas Dehghan, Konstantinos K. Tsilidis, The PRACTICAL consortium

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis.

Methods

Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer).

Results

There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses.

Conclusions

Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.

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Title: Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis
Authors: Emmanouil Bouras
Ville Karhunen
Dipender Gill
Jian Huang
Philip C. Haycock
Marc J. Gunter
Mattias Johansson
Paul Brennan
Tim Key
Sarah J. Lewis
Richard M. Martin
Neil Murphy
Elizabeth A. Platz
Ruth Travis
James Yarmolinsky
Verena Zuber
Paul Martin
Michail Katsoulis
Heinz Freisling
Therese Haugdahl Nøst
Matthias B. Schulze
Laure Dossus
Rayjean J. Hung
Christopher I. Amos
Ari Ahola-Olli
Saranya Palaniswamy
Minna Männikkö
Juha Auvinen
Karl-Heinz Herzig
Sirkka Keinänen-Kiukaanniemi
Terho Lehtimäki
Veikko Salomaa
Olli Raitakari
Marko Salmi
Sirpa Jalkanen
Marjo-Riitta Jarvelin
Abbas Dehghan
Konstantinos K. Tsilidis
The PRACTICAL consortium
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Lung Cancer
Lung Cancer
Ovarian Cancer
Ovarian Cancer
Cytokines
Lung Cancer
Endometrial Cancer
Endometrial Cancer
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-021-02193-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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