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

Kuvaus

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.
Näytä enemmän

Julkaisuvuosi

2022

Aineiston tyyppi

Tekijät

Terho Lehtimäki - Tekijä

Tuntematon organisaatio

Abbas Dehghan - Tekijä

Ari Ahola-Olli - Tekijä

Christopher I. Amos - Tekijä

Dipender Gill - Tekijä

Elizabeth A. Platz - Tekijä

Emmanouil Bouras - Tekijä

Heinz Freisling - Tekijä

James Yarmolinsky - Tekijä

Jian Huang - Tekijä

Juha Auvinen - Tekijä

Karl-Heinz Herzig - Tekijä

Konstantinos K. Tsilidis - Tekijä

Laure Dossus - Tekijä

Marc J. Gunter - Tekijä

Marjo-Riitta Jarvelin - Tekijä

Marko Salmi - Tekijä

Matthias B. Schulze - Tekijä

Mattias Johansson - Tekijä

Michail Katsoulis - Tekijä

Minna Männikkö - Tekijä

Neil Murphy - Tekijä

Olli Raitakari - Tekijä

Paul Brennan - Tekijä

Paul Martin - Tekijä

Philip C. Haycock - Tekijä

Rayjean J. Hung - Tekijä

Richard M. Martin - Tekijä

Ruth Travis - Tekijä

Sarah J. Lewis - Tekijä

Saranya Palaniswamy - Tekijä

Sirkka Keinänen-Kiukaanniemi - Tekijä

Sirpa Jalkanen - Tekijä

Therese Haugdahl Nøst - Tekijä

Tim Key - Tekijä

Veikko Salomaa - Tekijä

Verena Zuber - Tekijä

Ville Karhunen - Tekijä

figshare - Julkaisija

Projekti

Muut tiedot

Tieteenalat

Biolääketieteet

Kieli

englanti

Saatavuus

Avoin

Lisenssi

Creative Commons Nimeä 4.0 Kansainvälinen (CC BY 4.0)

Avainsanat

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

Asiasanat

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