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

Beskrivning

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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Publiceringsår

2022

Typ av data

Upphovspersoner

Terho Lehtimäki - Upphovsperson

Unknown organization

Abbas Dehghan - Upphovsperson

Ari Ahola-Olli - Upphovsperson

Christopher I. Amos - Upphovsperson

Dipender Gill - Upphovsperson

Elizabeth A. Platz - Upphovsperson

Emmanouil Bouras - Upphovsperson

Heinz Freisling - Upphovsperson

James Yarmolinsky - Upphovsperson

Jian Huang - Upphovsperson

Juha Auvinen - Upphovsperson

Karl-Heinz Herzig - Upphovsperson

Konstantinos K. Tsilidis - Upphovsperson

Laure Dossus - Upphovsperson

Marc J. Gunter - Upphovsperson

Marjo-Riitta Jarvelin - Upphovsperson

Marko Salmi - Upphovsperson

Matthias B. Schulze - Upphovsperson

Mattias Johansson - Upphovsperson

Michail Katsoulis - Upphovsperson

Minna Männikkö - Upphovsperson

Neil Murphy - Upphovsperson

Olli Raitakari - Upphovsperson

Paul Brennan - Upphovsperson

Paul Martin - Upphovsperson

Philip C. Haycock - Upphovsperson

Rayjean J. Hung - Upphovsperson

Richard M. Martin - Upphovsperson

Ruth Travis - Upphovsperson

Sarah J. Lewis - Upphovsperson

Saranya Palaniswamy - Upphovsperson

Sirkka Keinänen-Kiukaanniemi - Upphovsperson

Sirpa Jalkanen - Upphovsperson

Therese Haugdahl Nøst - Upphovsperson

Tim Key - Upphovsperson

Veikko Salomaa - Upphovsperson

Verena Zuber - Upphovsperson

Ville Karhunen - Upphovsperson

figshare - Utgivare

Projekt

Övriga uppgifter

Vetenskapsområden

Biomedicinska vetenskaper

Språk

engelska

Öppen tillgång

Öppet

Licens

Creative Commons Attribution 4.0 International (CC BY 4.0)

Nyckelord

genetics, Biotechnology, 19999 Mathematical Sciences not elsewhere classified, Medicine, FOS: Biological sciences, FOS: Clinical medicine, Immunology, FOS: Mathematics, 110309 Infectious Diseases, FOS: Health sciences

Ämnesord

Temporal täckning

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