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

  • Emmanouil Bouras (University of Ioannina School of Medicine) (Creator)
  • Ville Karhunen (Creator)
  • Dipender Gill (Creator)
  • Jian Huang (Imperial College, London, 24.8.2012) (Creator)
  • Philip C. Haycock (University of Bristol) (Creator)
  • Marc J. Gunter (International Agency for Research on Cancer) (Creator)
  • Mattias Johansson (International Agency for Research on Cancer) (Creator)
  • Paul Brennan (Creator)
  • Tim Key (Creator)
  • Sarah J. Lewis (Creator)
  • Richard M Martin (Creator)
  • Neil Murphy (International Agency for Research on Cancer) (Creator)
  • E. A. Platz (Creator)
  • Ruth C. Travis (Creator)
  • James Yarmolinsky (University of Bristol) (Creator)
  • Verena Zuber (Creator)
  • Paul Martin (University of Bristol) (Creator)
  • Michail Katsoulis (Department of Applied Health Research) (Creator)
  • Heinz Freisling (International Agency for Research on Cancer) (Creator)
  • Therese Haugdahl Nøst (UiT The Arctic University of Norway) (Creator)
  • Matthias B. Schulze (German Institute of Human Nutrition) (Creator)
  • Laure Dossus (International Agency for Research on Cancer) (Creator)
  • Rayjean J. Hung (University of Toronto, Canada) (Creator)
  • Christopher I. Amos (Baylor College of Medicine) (Creator)
  • Ari Ahola-Olli (Creator)
  • Saranya Palaniswamy (Imperial College, London, 24.8.2012) (Creator)
  • Minna Männikkö (Creator)
  • Juha Auvinen (Creator)
  • Karl-Heinz Herzig (Creator)
  • Sirkka Keinänen-Kiukaanniemi (Creator)
  • Terho Lehtimäki (Creator)
  • Veikko Salomaa (Creator)
  • Olli Raitakari (Creator)
  • Marko Salmi (Creator)
  • Sirpa Jalkanen (Creator)
  • Marjo-Riitta Jarvelin (Creator)
  • Abbas Dehghan (Creator)
  • Konstantinos K. Tsilidis (University of Ioannina School of Medicine) (Creator)



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.
Koska saatavilla11 tammik. 2022

Field of science, Statistics Finland

  • 3111 Biolääketieteet
  • Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis

    PRACTICAL Consortium, Bouras, E., Karhunen, V., Gill, D., Huang, J., Haycock, P. C., Gunter, M. J., Johansson, M., Brennan, P., Key, T., Lewis, S. J., Martin, R. M., Murphy, N., Platz, E. A., Travis, R., Yarmolinsky, J., Zuber, V., Martin, P., Katsoulis, M. & Freisling, H. & 19 muuta, Nøst, T. H., Schulze, M. B., Dossus, L., Hung, R. J., Amos, C. I., Ahola-Olli, A., Palaniswamy, S., Männikkö, M., Auvinen, J., Herzig, K.-H., Keinänen-Kiukaanniemi, S., Lehtimäki, T., Salomaa, V., Raitakari, O., Salmi, M., Jalkanen, S., Jarvelin, M.-R., Dehghan, A. & Tsilidis, K. K., 11 tammik. 2022, julkaisussa: Bmc Medicine. 20, 15 Sivumäärä, 3.

    Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

    Open access
    45 Sitaatiot (Scopus)

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