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Andrology. 2019 Jul;7(4):555-564. doi: 10.1111/andr.12667.

Runs of homozygosity and testicular cancer risk.

Author information

1
Division of Genetics & 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, UK.
12
Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, UK.
13
William Harvey Research Institute, Queen Mary University, London, UK.
14
Guys and St Thomas' NHS Foundation Trust, London, UK.
15
Public Health England, National Cancer Registration and Analysis Service, London, UK.

Abstract

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.

KEYWORDS:

cancer; genetics; genome-wide association studies; homozygosity mapping; recessive; runs of homozygosity; testicular germ cell tumour

PMID:
31310061
DOI:
10.1111/andr.12667

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