Karina Dalsgaard Sørensen

Runs of homozygosity and testicular cancer risk

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • C Loveday, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • A Sud, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • K Litchfield, Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
  • ,
  • M Levy, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • A Holroyd, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • P Broderick, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • Z Kote-Jarai, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • A M Dunning, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • ,
  • K Muir, Institute of Population Health, University of Manchester, Manchester, England.
  • ,
  • J Peto, Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
  • ,
  • R Eeles, Royal Marsden NHS Fdn Trust, Royal Marsden NHS Foundation Trust, The Royal Marsden Hospital - London
  • ,
  • D F Easton, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge.
  • ,
  • D Dudakia, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • N Orr, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP, UK.
  • ,
  • N Pashayan, Department of Applied Health Research, University College London, UK.
  • ,
  • UK Testicular Cancer Collaboration
  • ,
  • The PRACTICAL Consortium
  • ,
  • A Reid, Academic Uro-oncology Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
  • ,
  • R A Huddart, Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK.
  • ,
  • R S Houlston, Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • ,
  • C Turnbull, National Cancer Registration and Analysis Service, Public Health England, Skipton House, 80 London Road, London SE1 6LH, UK.

BACKGROUND: Testicular germ cell tumour (TGCT) is highly heritable but > 50% of the genetic risk remains unexplained. Epidemiological observation of greater relative risk to brothers of men with TGCT compared to sons has long alluded to recessively acting TGCT genetic susceptibility factors, but to date none have been reported. Runs of homozygosity (RoH) are a signature indicating underlying recessively acting alleles and have been associated with increased risk of other cancer types.

OBJECTIVE: To examine whether RoH are associated with TGCT risk.

METHODS: We performed a genome-wide RoH analysis using GWAS data from 3206 TGCT cases and 7422 controls uniformly genotyped using the OncoArray platform.

RESULTS: Global measures of homozygosity were not significantly different between cases and controls, and the frequency of individual consensus RoH was not significantly different between cases and controls, after correction for multiple testing. RoH at three regions, 11p13-11p14.3, 5q14.1-5q22.3 and 13q14.11-13q.14.13, were, however, nominally statistically significant at p < 0.01. Intriguingly, RoH200 at 11p13-11p14.3 encompasses Wilms tumour 1 (WT1), a recognized cancer susceptibility gene with roles in sex determination and developmental transcriptional regulation, processes repeatedly implicated in TGCT aetiology.

DISCUSSION AND CONCLUSION: Overall, our data do not support a major role in the risk of TGCT for recessively acting alleles acting through homozygosity, as measured by RoH in outbred populations of cases and controls.

Original languageEnglish
JournalAndrology
Volume7
Issue4
Pages (from-to)555-564
Number of pages10
ISSN2047-2919
DOIs
Publication statusPublished - Jul 2019

See relations at Aarhus University Citationformats

ID: 186719379