Immune cells mediate the causal pathway linking circulating complements to cancer: A Mendelian randomization study

Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, Harvey JD, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: a systematic analysis for the global burden of disease study 2019. JAMA Oncol. 2022;8:420–44.

Article  PubMed  Google Scholar 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians 2021; 71:209–249.

Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I - molecular mechanisms of activation and regulation. Front Immunol. 2015;6:262.

Article  PubMed  PubMed Central  Google Scholar 

Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11:785–97.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Afshar-Kharghan V. The role of the complement system in cancer. J Clin Investig. 2017;127:780–9.

Article  PubMed  PubMed Central  Google Scholar 

Ricklin D, Reis ES, Lambris JD. Complement in disease: a defence system turning offensive. Nat Rev Nephrol. 2016;12:383–401.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Pio R, Ajona D, Lambris JD. Complement inhibition in cancer therapy. Semin Immunol. 2013;25:54–64.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, et al. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell. 2015;160:700–14.

Article  PubMed  CAS  Google Scholar 

Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, et al. Modulation of the antitumor immune response by complement. Nat Immunol. 2008;9:1225–35.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Vadrevu SK, Chintala NK, Sharma SK, Sharma P, Cleveland C, Riediger L, et al. Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche. Can Res. 2014;74:3454–65.

Article  CAS  Google Scholar 

Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37:658–65.

Article  PubMed  PubMed Central  Google Scholar 

Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA. 2017;318:1925–6.

Article  PubMed  Google Scholar 

Burgess S, Scott RA, Timpson NJ, Davey Smith G, Thompson SG. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol. 2015;30:543–52.

Article  PubMed  PubMed Central  Google Scholar 

Davies NM, Holmes MV, Davey SG. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018;362: k601.

Article  PubMed  PubMed Central  Google Scholar 

Sun BB, Chiou J, Traylor M, Benner C, Hsu YH, Richardson TG, et al. Plasma proteomic associations with genetics and health in the UK Biobank. Nature. 2023;622:329–38.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ferkingstad E, Sulem P, Atlason BA, Sveinbjornsson G, Magnusson MI, Styrmisdottir EL, et al. Large-scale integration of the plasma proteome with genetics and disease. Nat Genet. 2021;53:1712–21.

Article  PubMed  CAS  Google Scholar 

Orrù V, Steri M, Sidore C, Marongiu M, Serra V, Olla S, et al. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet. 2020;52:1036–45.

Article  PubMed  PubMed Central  Google Scholar 

Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, et al. Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets. Nat Immunol. 2023;24:1540–51.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Martin RM, Lewis SJ, et al. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis. Nat Commun. 2020;11:597.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bowden J, Del Greco MF, Minelli C, Davey Smith G, Sheehan NA, Thompson JR. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic. Int J Epidemiol. 2016;45:1961–74.

PubMed  PubMed Central  Google Scholar 

Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:377–89.

Article  PubMed  PubMed Central  Google Scholar 

Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol. 2013;178:1177–84.

Article  PubMed  PubMed Central  Google Scholar 

Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46:1985–98.

Article  PubMed  PubMed Central  Google Scholar 

Zhao J, Ming J, Hu X, Chen G, Liu J, Yang C. Bayesian weighted Mendelian randomization for causal inference based on summary statistics. Bioinformatics. 2020;36:1501–8.

Article  PubMed  CAS  Google Scholar 

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

Article  PubMed  PubMed Central  Google Scholar 

Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693–8.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Oka R, Sasagawa T, Ninomiya I, Miwa K, Tanii H, Saijoh K. Reduction in the local expression of complement component 6 (C6) and 7 (C7) mRNAs in oesophageal carcinoma. Eur J Cancer. 2001;37:1158–65.

Article  PubMed  CAS  Google Scholar 

Zhou Z, Jia D, Kwon O, Li S, Sun H, Roudier MP, et al. Androgen-regulated stromal complement component 7 (C7) suppresses prostate cancer growth. Oncogene. 2023;42:2428–38.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bharti R, Dey G, Lin F, Lathia J, Reizes O. CD55 in cancer: Complementing functions in a non-canonical manner. Cancer Lett. 2022;551: 215935.

Article  PubMed  PubMed Central  CAS  Google Scholar 

He Z, Wu H, Jiao Y, Zheng J. Expression and prognostic value of CD97 and its ligand CD55 in pancreatic cancer. Oncol Lett. 2015;9:793–7.

Article  PubMed  Google Scholar 

Zhao L, Zhang Z, Lin J, Cao L, He B, Han S, et al. Complement receptor 1 genetic variants contribute to the susceptibility to gastric cancer in Chinese population. J Cancer. 2015;6:525–30.

Article  PubMed  PubMed Central 

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