Validation of loci at 2q14.2 and 15q21.3 as risk factors for testicular cancer
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Chey Loveday1, Kevin Litchfield1,2, Max Levy1, Amy Holroyd1, Peter Broderick1, Zsofia Kote-Jarai1, Alison M Dunning3, Kenneth Muir4,5, Julian Peto6, Rosalind Eeles1,7, Douglas F Easton3,8, Darshna Dudakia1, Nick Orr9, Nora Pashayan10, Alison Reid11, Robert A Huddart12, Richard S Houlston1 and Clare Turnbull1,13,14,15
1Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
2Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK
3Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
4Division of Health Sciences, Warwick Medical School, Warwick University, Warwick, UK
5Institute of Population Health, University of Manchester, Manchester, UK
6Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
7Royal Marsden NHS Foundation Trust, London, UK
8Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
9The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
10Department of Applied Health Research, University College London, London, UK
11Academic Uro-oncology Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
12Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK
13William Harvey Research Institute, Queen Mary University, London, UK
14Guys and St Thomas NHS Foundation Trust, London, UK
15National Cancer Registration and Analysis Service, Public Health England, London, UK
Clare Turnbull, email: [email protected]
Keywords: testicular cancer; germ cell tumor; TGCT; GWAS; oncoarray
Received: July 12, 2017 Accepted: November 15, 2017 Published: December 07, 2017
Testicular germ cell tumor (TGCT), the most common cancer in men aged 18 to 45 years, has a strong heritable basis. Genome-wide association studies (GWAS) have proposed single nucleotide polymorphisms (SNPs) at a number of loci influencing TGCT risk. To further evaluate the association of recently proposed risk SNPs with TGCT at 2q14.2, 3q26.2, 7q36.3, 10q26.13 and 15q21.3, we analyzed genotype data on 3,206 cases and 7,422 controls. Our analysis provides independent replication of the associations for risk SNPs at 2q14.2 (rs2713206 at P = 3.03 x 10–2; P-meta = 3.92 x 10–8; nearest gene, TFCP2L1) and rs12912292 at 15q21.3 (P = 7.96 x 10–11; P-meta = 1.55 x 10–19; nearest gene PRTG). Case-only analyses did not reveal specific associations with TGCT histology. TFCP2L1 joins the growing list of genes located within TGCT risk loci with biologically plausible roles in developmental transcriptional regulation, further highlighting the importance of this phenomenon in TGCT oncogenesis.
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