iScience (Jul 2020)
Immune Cell Associations with Cancer Risk
- Luis Palomero,
- Ivan Galván-Femenía,
- Rafael de Cid,
- Roderic Espín,
- Daniel R. Barnes,
- CIMBA,
- Eline Blommaert,
- Miguel Gil-Gil,
- Catalina Falo,
- Agostina Stradella,
- Dan Ouchi,
- Albert Roso-Llorach,
- Concepció Violan,
- María Peña-Chilet,
- Joaquín Dopazo,
- Ana Isabel Extremera,
- Mar García-Valero,
- Carmen Herranz,
- Francesca Mateo,
- Elisabetta Mereu,
- Jonathan Beesley,
- Georgia Chenevix-Trench,
- Cecilia Roux,
- Tak Mak,
- Joan Brunet,
- Razq Hakem,
- Chiara Gorrini,
- Antonis C. Antoniou,
- Conxi Lázaro,
- Miquel Angel Pujana
Affiliations
- Luis Palomero
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Ivan Galván-Femenía
- 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
- 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
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Daniel R. Barnes
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
- CIMBA
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
- Eline Blommaert
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Miguel Gil-Gil
- Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Catalina Falo
- Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Agostina Stradella
- Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Dan Ouchi
- 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
- 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
- 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
- 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
- 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
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Mar García-Valero
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Carmen Herranz
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Francesca Mateo
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain
- Elisabetta Mereu
- CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Catalonia 08003, Spain
- Jonathan Beesley
- Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
- Georgia Chenevix-Trench
- Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
- Cecilia Roux
- 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
- 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
- Hereditary Cancer Program, Catalan Institute of Oncology, Biomedical Research Institute of Girona (IDIBGI), Girona, Catalonia 17190, Spain
- Razq Hakem
- Princess Margaret Cancer Centre, Department of Medical Biophysics, University Health Network and University of Toronto, Toronto, ON M5G 2C1, Canada
- Chiara Gorrini
- 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
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Corresponding author
- Conxi Lázaro
- 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; Corresponding author
- Miquel Angel Pujana
- ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain; Corresponding author
- Journal volume & issue
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Vol. 23,
no. 7
p. 101296
Abstract
Summary: 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.
