Immune Cell Associations with Cancer Risk.

Cancer Cancer Systems Biology Immunology

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
24 Jul 2020
Historique:
received: 18 03 2020
revised: 23 05 2020
accepted: 15 06 2020
pubmed: 6 7 2020
medline: 6 7 2020
entrez: 5 7 2020
Statut: ppublish

Résumé

Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features. Polygenic risk scores also reveal associations with immune and/or stromal cell contents, and breast cancer scores show consistent results in normal and tumor tissue. SH2B3 links peripheral alterations of several immune cell types to the risk of this malignancy. Pleiotropic SH2B3 variants are associated with breast cancer risk in BRCA1/2 mutation carriers. A retrospective case-cohort study indicates a positive association between blood counts of basophils, leukocytes, and monocytes and age at breast cancer diagnosis. These findings broaden our knowledge of the role of the immune system in cancer and highlight promising prevention strategies for individuals at high risk.

Identifiants

DOI: 10.1016/j.isci.2020.101296 PMID: 32622267 PMC: PMC7334419
pubmed: 32622267
pii: S2589-0042(20)30483-1
doi: 10.1016/j.isci.2020.101296
pmc: PMC7334419
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

101296

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests M.A.P. is recipient of an unrestricted research grant from Roche Pharma for the development of the ProCURE ICO research program. C.F. received support from Pfizer unrelated to this study.

Références

Nat Biotechnol. 2019 Jul;37(7):773-782
pubmed: 31061481
Nat Genet. 2017 Aug;49(8):1182-1191
pubmed: 28628107
Cancer Res. 2017 Apr 1;77(7):1510-1541
pubmed: 28373404
Matrix Biol. 2014 Jul;37:69-82
pubmed: 24582666
Mol Syst Biol. 2015 Apr 16;11(1):799
pubmed: 25882670
Cell. 2018 Apr 5;173(2):400-416.e11
pubmed: 29625055
Nat Genet. 2013 Oct;45(10):1113-20
pubmed: 24071849
J Clin Invest. 2014 Jan;124(1):398-412
pubmed: 24316975
J Immunol. 2000 May 15;164(10):5199-206
pubmed: 10799879
Prog Exp Tumor Res. 1970;13:1-27
pubmed: 4921480
J Autoimmun. 2016 Jan;66:25-39
pubmed: 26347073
Semin Cancer Biol. 2015 Dec;35 Suppl:S185-S198
pubmed: 25818339
Leukemia. 2017 Aug;31(8):1661-1670
pubmed: 28484264
PLoS Genet. 2017 Mar 1;13(3):e1006643
pubmed: 28248954
J Immunol. 2015 Jan 1;194(1):35-42
pubmed: 25404367
Immunity. 2008 Apr;28(4):571-80
pubmed: 18394936
Cancer Cell. 2018 Apr 9;33(4):676-689.e3
pubmed: 29622463
Genes Dev. 2018 Oct 1;32(19-20):1267-1284
pubmed: 30275043
Cancer Res. 2016 Sep 1;76(17):5103-14
pubmed: 27197191
Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4
pubmed: 22064851
J Clin Invest. 2015 Sep;125(9):3347-55
pubmed: 26325032
Development. 1999 May;126(10):2215-25
pubmed: 10207146
Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11701-E11710
pubmed: 30463956
Clin Exp Immunol. 2016 Jul;185(1):1-21
pubmed: 26919392
Cell. 2016 Nov 17;167(5):1415-1429.e19
pubmed: 27863252
Mol Immunol. 2008 Oct;45(16):4064-72
pubmed: 18926283
JAMA Netw Open. 2020 Jan 3;3(1):e1919536
pubmed: 31951276
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
J Exp Med. 2002 Jun 17;195(12):1599-611
pubmed: 12070287
J Natl Cancer Inst. 2015 Aug 29;107(11):
pubmed: 26319099
Immunity. 2018 Apr 17;48(4):812-830.e14
pubmed: 29628290
Cancer Res. 2018 Nov 1;78(21):6059-6072
pubmed: 30135189
Cancer Res. 2019 Dec 15;79(24):6238-6246
pubmed: 31641033
Front Immunol. 2016 Sep 20;7:365
pubmed: 27703456
Front Immunol. 2016 Dec 20;7:621
pubmed: 28066431
J Immunol. 2013 Jul 15;191(2):892-901
pubmed: 23776175
Oncotarget. 2017 Jan 24;8(4):7175-7180
pubmed: 27764780
J Natl Cancer Inst. 2013 May 1;105(9):624-33
pubmed: 23482656
Breast Cancer Res. 2017 Jan 5;19(1):2
pubmed: 28057046
Nat Genet. 2016 Jan;48(1):74-8
pubmed: 26642240
Bioinformatics. 2018 Jun 1;34(11):1969-1979
pubmed: 29351586
Nature. 2017 Nov 2;551(7678):92-94
pubmed: 29059683
Arch Intern Med. 2007 Sep 24;167(17):1837-44
pubmed: 17893304
Yale J Biol Med. 1982 May-Aug;55(3-4):329-33
pubmed: 6758376
Nat Rev Genet. 2018 Sep;19(9):581-590
pubmed: 29789686
Nat Commun. 2017 May 24;8:15382
pubmed: 28537254
Am J Hum Genet. 2018 Jun 7;102(6):1048-1061
pubmed: 29779563

Auteurs

Luis Palomero (L)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Ivan Galván-Femenía (I)

GCAT-Genomes for Life, Germans Trias i Pujol Health Sciences Research Institute (IGTP), Program for Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Catalonia 08916, Spain.

Rafael de Cid (R)

GCAT-Genomes for Life, Germans Trias i Pujol Health Sciences Research Institute (IGTP), Program for Predictive and Personalized Medicine of Cancer (IMPPC), Badalona, Catalonia 08916, Spain.

Roderic Espín (R)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Daniel R Barnes (DR)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.

Eline Blommaert (E)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Miguel Gil-Gil (M)

Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Catalina Falo (C)

Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Agostina Stradella (A)

Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Dan Ouchi (D)

Jordi Gol University Institute for Research Primary Healthcare (IDIAP Jordi Gol), Barcelona, Catalonia 08007, Spain; Autonomous University of Barcelona, Bellaterra, Catalonia 08913, Spain.

Albert Roso-Llorach (A)

Jordi Gol University Institute for Research Primary Healthcare (IDIAP Jordi Gol), Barcelona, Catalonia 08007, Spain; Autonomous University of Barcelona, Bellaterra, Catalonia 08913, Spain.

Concepció Violan (C)

Jordi Gol University Institute for Research Primary Healthcare (IDIAP Jordi Gol), Barcelona, Catalonia 08007, Spain; Autonomous University of Barcelona, Bellaterra, Catalonia 08913, Spain.

María Peña-Chilet (M)

Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), Bioinformatics in Rare Diseases (BiER), CIBERER, INB-ELIXIR-es, Hospital Virgen del Rocío, Seville 41013, Spain.

Joaquín Dopazo (J)

Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), Bioinformatics in Rare Diseases (BiER), CIBERER, INB-ELIXIR-es, Hospital Virgen del Rocío, Seville 41013, Spain.

Ana Isabel Extremera (AI)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Mar García-Valero (M)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Carmen Herranz (C)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Francesca Mateo (F)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain.

Elisabetta Mereu (E)

CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Catalonia 08003, Spain.

Jonathan Beesley (J)

Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.

Georgia Chenevix-Trench (G)

Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.

Cecilia Roux (C)

Princess Margaret Cancer Centre, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada.

Tak Mak (T)

Princess Margaret Cancer Centre, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada.

Joan Brunet (J)

Hereditary Cancer Program, Catalan Institute of Oncology, Biomedical Research Institute of Girona (IDIBGI), Girona, Catalonia 17190, Spain.

Razq Hakem (R)

Princess Margaret Cancer Centre, Department of Medical Biophysics, University Health Network and University of Toronto, Toronto, ON M5G 2C1, Canada.

Chiara Gorrini (C)

Princess Margaret Cancer Centre, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada.

Antonis C Antoniou (AC)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. Electronic address: aca20@medschl.cam.ac.uk.

Conxi Lázaro (C)

Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, and Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid 28029, Spain. Electronic address: clazaro@iconcologia.net.

Miquel Angel Pujana (MA)

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain. Electronic address: mapujana@iconcologia.net.

Classifications MeSH