1. Runs of homozygosity and testicular cancer risk
- Author
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Loveday, C, Sud, A, Litchfield, K, Levy, M, Holroyd, A, Broderick, P, Kote-Jarai, Z, Dunning, AM, Muir, K, Peto, J, Eeles, R, Easton, DF, Dudakia, D, Orr, N, Pashayan, N, Rustin, Gordon, Srihari, Narayanan N, Cole, David, Askill, Colin, Bertelli, Gianfilippo, Barber, James, Gilby, Ed, White, Jeff, Baybrooke, Jeremy, Leahy, Michael, Welch, Richard, Chakraborti, Prabir, Joffe, Johnathan, Brown, Richard, Faust, Guy, Simmonds, Peter, Mazhar, Danish, Stockdale, Andrew, Hrounda, David, Humber, Caroline, Appel, Wiebke, Hong, Anne, Howard, Grahame, Douglas, Fiona, Bloomfield, David, Butt, Mohammad, Kelly, Kay, Mehra, Rakesh, Rogers, Paul, Hatton, Matthew, Hennig, Ivo, McAteer, John, Savage, Philip, Seckl, Michael, Gale, Joanna, Clark, Peter, Woby, Steve, Rathmell, Adrian, Lamont, Alan, Sarwar, Naveed, Stuart, Nick, Chowdhury, Simon, Beesley, Sharon, Winkler, Mathius, Hamid, Abdel, Pathak, Sanjeev, Madhavan, Krishnaswamy, Highley, Martin, Money-Kryle, Julian, Brock, Cathryn, Sreenivasan, Thiagarajan, Henderson, Brian E, Haiman, Christopher A, Schumacher, Fredrick R, Al Olama, Ali Amin, Benlloch, Sara, Berndt, Sonja I, Conti, David V, Wiklund, Fredrik, Chanock, Stephen, Gapster, Susan, Stevens, Victoria L, Tangen, Catherine M, Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Schleutker, Johanna, Albanes, Demetrius, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Geraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, Maehle, Lovise, Neal, David E, Hamdy, Freddie C, Donovan, Jenny L, Travis, Ruth C, Hamilton, Robert J, Ingles, Sue Ann, Rosenstein, Barry S, Lu, Yong-Jie, Giles, Graham G, Kibel, Adam S, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L, Park, Jong Y, Stanford, Janet L, Cybulski, Cezary, Nordestgaard, Borge G, Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M, Teixeira, Manuel R, Neuhausen, Susan L, De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F, Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A, Dominguez, Manuela Gago, Roobol, Monique J, Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albrigh, Lisa, Pandha, Hardev, Thibodeau, Stephen N, Reid, A, Huddart, RA, Houlston, RS, Turnbull, C, and Urology
- Subjects
Oncology ,Male ,Endocrinology, Diabetes and Metabolism ,LOCI ,Genome-wide association study ,Runs of Homozygosity ,SUSCEPTIBILITY ,VARIANTS ,0302 clinical medicine ,Endocrinology ,testicular germ cell tumour ,Risk Factors ,Genotype ,genetics ,Andrology ,030219 obstetrics & reproductive medicine ,Genome ,Homozygote ,Neoplasms, Germ Cell and Embryonal ,Disease gene identification ,homozygosity mapping ,Life Sciences & Biomedicine ,RECENT POSITIVE SELECTION ,medicine.medical_specialty ,Urology ,Biology ,BREAST ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Endocrinology & Metabolism ,Testicular Neoplasms ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Genetic predisposition ,cancer ,Humans ,Allele ,GENOME-WIDE ASSOCIATION ,SEX DETERMINATION ,runs of homozygosity ,Science & Technology ,IDENTIFICATION ,Cancer ,recessive ,medicine.disease ,GERM-CELL TUMOR ,CONSANGUINITY ,Reproductive Medicine ,Relative risk ,genome-wide association studies ,Genome-Wide Association Study - 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
- Published
- 2019
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