Validation of loci at 2q14.2 and 15q21.3 as risk factors for testicular cancer

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 atP= 3.03 × 10-2;P-meta = 3.92 × 10-8; nearest gene, TFCP2L1) and rs12912292 at 15q21.3 (P= 7.96 × 10-11;P-meta = 1.55 × 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.

Oncotarget. 2017 Dec 07*** epublish ***

Chey Loveday, Kevin Litchfield, Max Levy, Amy Holroyd, Peter Broderick, Zsofia Kote-Jarai, Alison M Dunning, Kenneth Muir, Julian Peto, Rosalind Eeles, Douglas F Easton, Darshna Dudakia, Nick Orr, Nora Pashayan, Alison Reid, Robert A Huddart, Richard S Houlston, Clare Turnbull

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Division of Health Sciences, Warwick Medical School, Warwick University, Warwick, UK., Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK., The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK., Department of Applied Health Research, University College London, London, UK., Academic Uro-oncology Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK., Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK.

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