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

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

doi:10.18632/oncotarget.23117

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

Oncotarget. 2017 Dec 7;9(16):12630-12638. doi: 10.18632/oncotarget.23117. eCollection 2018 Feb 27.

Authors

Chey Loveday¹, Kevin Litchfield^{1

2}, Max Levy¹, Amy Holroyd¹, Peter Broderick¹, Zsofia Kote-Jarai¹, Alison M Dunning³, Kenneth Muir^{4

5}, Julian Peto⁶, Rosalind Eeles^{1

7}, Douglas F Easton^{3

8}, Darshna Dudakia¹, Nick Orr⁹, Nora Pashayan¹⁰, Alison Reid¹¹, Robert A Huddart¹², Richard S Houlston¹, Clare Turnbull^{1

13

14

15}

Affiliations

¹ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
² Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
³ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁴ Division of Health Sciences, Warwick Medical School, Warwick University, Warwick, UK.
⁵ Institute of Population Health, University of Manchester, Manchester, UK.
⁶ Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
⁷ Royal Marsden NHS Foundation Trust, London, UK.
⁸ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁹ The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
¹⁰ Department of Applied Health Research, University College London, London, UK.
¹¹ Academic Uro-oncology Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
¹² Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK.
¹³ William Harvey Research Institute, Queen Mary University, London, UK.
¹⁴ Guys and St Thomas NHS Foundation Trust, London, UK.
¹⁵ National Cancer Registration and Analysis Service, Public Health England, London, UK.

Abstract

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 × 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.

Keywords: GWAS; TGCT; germ cell tumor; oncoarray; testicular cancer.

Abstract

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