Runs of homozygosity and testicular cancer risk. (16th July 2019)

• Record Type: Journal Article
• Authors: Loveday, C.; Sud, A.; Litchfield, K.; Levy, M.; Holroyd, A.; Broderick, P.; Kote‐Jarai, Z.; Dunning, A. M.; Muir, K.; Peto, J.; Eeles, R.; Easton, D. F.; Dudakia, D.; Orr, N.; Pashayan, N.; Reid, A.; Huddart, R. A.; Houlston, R. S.; Turnbull, C.
• Other Names: Rustin Gordon investigator.; Srihari Narayanan N investigator.; Cole David investigator.; Askill Colin investigator.; Bertelli Gianfilippo investigator.; Barber James investigator.; Gilby Ed investigator.; White Jeff investigator.; Baybrooke Jeremy investigator.; Leahy Michael investigator.; Welch Richard investigator.; Chakraborti Prabir investigator.; Joffe Johnathan investigator.; Brown Richard investigator.; Faust Guy investigator.; Simmonds Peter investigator.; Mazhar Danish investigator.; Stockdale Andrew investigator.; Hrounda David investigator.; Humber Caroline investigator.; Appel Wiebke investigator.; Hong Anne investigator.; Howard Grahame investigator.; Douglas Fiona investigator.; Bloomfield David investigator.; Butt Mohammad investigator.; Kelly Kay investigator.; Mehra Rakesh investigator.; Brown Richard investigator.; Rogers Paul investigator.; Chakraborti Prabir investigator.; Hatton Matthew investigator.; Hennig Ivo investigator.; McAteer John investigator.; Savage Philip investigator.; Seckl Michael investigator.; Gale Joanna investigator.; Rustin Gordon investigator.; Clark Peter investigator.; Woby Steve investigator.; Rathmell Adrian investigator.; Lamont Alan investigator.; Sarwar Naveed investigator.; Stuart Nick investigator.; Chowdhury Simon investigator.; Beesley Sharon investigator.; Winkler Mathius investigator.; Hamid Abdel investigator.; Pathak Sanjeev investigator.; Madhavan Krishnaswamy investigator.; Highley Martin investigator.; Money‐Kryle Julian investigator.; Brock Cathryn investigator.; Sreenivasan Thiagarajan investigator.; Dalsgaard Sorensen Karina investigator.; Maehle Lovise investigator.; Neal David E investigator.; Hamdy Freddie C investigator.; Donovan Jenny L investigator.; Travis Ruth C investigator.; Hamilton Robert J investigator.; Ann Ingles Sue investigator.; Rosenstein Barry S investigator.; Lu Yong‐Jie investigator.; Giles Graham G investigator.; Kibel Adam S investigator.; Vega Ana investigator.; Kogevinas Manolis investigator.; Park Jong Y investigator.; Stanford Janet L investigator.; Cybulski Cezary investigator.; Nordestgaard Børge G investigator.; Brenner Hermann investigator.; Maier Christiane investigator.; Kim Jeri investigator.; John Esther M investigator.; Teixeira Manuel R investigator.; Neuhausen Susan L investigator.; De Ruyck Kim investigator.; Razack Azad investigator.; Newcomb Lisa F investigator.; Lessel Davor investigator.; Kaneva Radka investigator.; Usmani Nawaid investigator.; Claessens Frank investigator.; Townsend Paul A investigator.; Gago Dominguez Manuela investigator.; Roobol Monique J investigator.; Menegaux Florence investigator.; Khaw Kay‐Tee investigator.; Cannon‐Albrigh Lisa investigator.; Pandha Hardev investigator.; Thibodeau Stephen N investigator.; Rajpert‐De Meyts Ewa guestEditor.;
• Is Part Of: Andrology. Volume 7:Number 4(2019)
• Page Start: 555
• Page End: 564
• Publication Date: 2019-07-16
• Subjects: cancer -- genetics -- genome‐wide association studies -- homozygosity mapping -- recessive -- runs of homozygosity -- testicular germ cell tumour; Andrology -- Periodicals; 616.65
• DOI: 10.1111/andr.12667
• Languages: English
• ISSNs: 2047-2919

Abstract

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.