E047 – Cancer Genetics and Epidemiology Group

Objectives

1. Implementation and development of genomic studies of cancer in Galicia:
– Breast cancer: BREast Oncology GAlicia Network (BREOGAN). This genetic-epidemiological study has exhaustive data and samples from more than 2,000 breast cancer patients and 2,000 controls. Includes: (i) Population-based study. (ii) Study to develop new risk/diagnostic markers. (iii) Study in males. (iv) Clinical trial of vitamin D and (v) Evaluation of the effect of the Microbiome on the etiology and response to standard oncological treatment of breast cancer.
– Colorectal cancer: GALicia COlon ONcology Study (GALEON). 500 patients and 1000 controls.
– Bladder cancer: Galicia Bladder Cancer Study (GBCS). 500 patients and 800 controls.
– Prostate cancer: PRostate Cancer Associations Genetics Galicia (PRAGGA). 700 patients and 1000 controls.

2. Inclusion in international genetic and genomic initiatives:
OncoArray global initiative, other GWAS, European Horizon 2020 B-CAST/BRIDGES projects, through which hundreds of genetic variants of susceptibility to breast, prostate, colorectal, bladder, acute lymphoblastic leukemia, Hodgkin’s lymphoma, have been identified. multiple myeloma and testicular cancer.

Lines of research

1. Genetic-epidemiological research on cancer in Galicia: breast cancer (BREOGAN), prostate cancer (PRAGGA), colorectal cancer (GALEON), bladder cancer (GBCS). GWAS studies, sequencing studies, B-CAST (http://www.b-cast.eu/), BRIDGES (BReast Cancer RIsk after Diagnostic Gene Sequencing, https://bridges-research.eu/) are performed.

2. Development and Implementation of BOADICEA and PRS as a screening tool in the Galician population.

3. Project ISCIII PI17/00918: Oxidative stress-induced apoptosis pathway in breast cancer: biochemical and Mendelian Randomization analysis.

4. Chemo-prevention of cancer. Clinical trial of vitamin D in women at high risk of breast cancer.

5. Studies of genetic epidemiology of stomach and lung cancer. Its objectives are to recruit young patients diagnosed with stomach cancer, and non-smokers diagnosed with lung adenocarcinoma, and to identify genomic signatures associated with these neoplasms.

6. Microbiome in breast cancer. Evaluation of the effect of the Microbiome on the etiology and response to standard oncological treatment of breast cancer.

7. Genetic determinants of Coronavirus infection. Through a consortium of 8,000 patients, we will study the genetic and genomic determinants of COVID-19 infection.

• Breast Cancer Association Consortium, Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, …, Gago-Dominguez M, Georgoulias V, Gil F, Giles GG, Glendon G, Garcia EBG, Alnæs GIG, Guénel P, Hadjisavvas A, Haeberle L, Hahnen E, Hall P, Hamann U, Harkness EF, Hartikainen JM, Hartman M, He W, Heemskerk-Gerritsen BAM, Hillemanns P, van Asperen CJ, Van Dam RM, van den Ouweland AMW, van der Kolk LE, van Veen EM, Wendt C, Williams JA, Yang XR, Yoon SY, Zamora MP, Evans DG, de la Hoya M, Simard J, Antoniou AC, Borg Å, Andrulis IL, Chang-Claude J, García-Closas M, Chenevix-Trench G, Milne RL, Pharoah PDP, Schmidt MK, Spurdle AB, Vreeswijk MPG, Benitez J, Dunning AM, Kvist A, Teo SH, Devilee P, Easton DF. Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women. New Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948
• Ruth KS, Day FR, Hussain J, Martínez-Marchal A, Aiken CE, Azad A,…Gago-Dominguez M, …Biobank-based Integrative Omics Study (BIOS) Consortium; eQTLGen Consortium; Biobank Japan Project; China Kadoorie Biobank Collaborative Group; kConFab Investigators; LifeLines Cohort Study; InterAct consortium; 23andMe Research Team, Chen Z, Li L, Franke L, Burgess S, Deelen P, Pers TH, Grøndahl ML, Andersen CY, Pujol A, Lopez-Contreras AJ, Daniel JA, Stefansson K, Chang-Claude J, van der Schouw YT, Lunetta KL, Chasman DI, Easton DF, Visser JA, Ozanne SE, Namekawa SH, Solc P, Murabito JM, Ong KK, Hoffmann ER, Murray A, Roig I, Perry JRB. Genetic insights into biological mechanisms governing human ovarian ageing. Nature. 2021 Aug;596(7872):393-397. doi: 10.1038/s41586-021-03779-7. Epub 2021 Aug 4.PMID: 34349265.
• Fachal L, Aschard H, Beesley J…Gago-Dominguez M, Gambino G, Ganz PA, Gapstur S, … Easton DF, Kraft P, Dunning AM. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature Genetics 2020 Jan;52(1):56-73. doi: 10.1038/s41588-019-0537-1. Epub 2020 Jan 7.
• Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, Castelao JE, Wiklund F, Nakagawa H, Gago-Dominguez M, Witte JS, Eeles RA, Kote-Jarai Z, Haiman CA. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nature Genetics. 2021 Jan;53(1):65-75.
• Zhang H, Ahearn TU, Lecarpentier J, Barnes D, Beesley J, Qi G, Jiang X, Castelao JE, Michailidou K, Antoniou AC, Schmidt MK, Gago-Dominguez M, Chenevix-Trench G, Easton DF, Chatterjee N, García-Closas M. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nature Genetics. 2020 Jun;52(6):572-581.
• Archambault AN, Su YR, Jeon J, Thomas M, Lin Y, Conti DV, Castelao JE, Gago-Dominguez M, Muñoz-Garzón V, Schoen RE, Hampel H, Corley DA, Hsu L, Peters U, Hayes RB. Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer. Gastroenterology. 2020 Apr;158(5):1274-1286.e12.
• Schumacher FR, Al Olama AA, Berndt SI, …, Aukim-Hastie C, Gago-Dominguez M, Castelao JE, …, Kote-Jarai Z, Haiman CA, Eeles RA. Association analysis of more than 145,000 men identifies 63 new prostate cancer susceptibility loci. PMID: 29892016. Nature Genetics. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Erratum in: Nat Genet. 2019 Feb;51(2):363.
• Gago-Dominguez M, Marcos Matabuena, Carmen M Redondo, Sandip Pravin Patel, Angel Carracedo, Sara Miranda Ponte, María Elena Martínez, J Esteban Castelao. Neutrophil to lymphocyte ratio and breast cancer risk: analysis by subtype and potential interactions. Sci Rep 2020 Aug 6;10(1):13203. doi: 10.1038/s41598-020-70077-z.PMID: 32764699.