Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.
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Date
2013-06-01Author
Ruark, E
Seal, S
McDonald, H
Zhang, F
Elliot, A
Lau, K
Perdeaux, E
Rapley, E
Eeles, R
Peto, J
Kote-Jarai, Z
Muir, K
Nsengimana, J
Shipley, J
UK Testicular Cancer Collaboration (UKTCC),
Bishop, DT
Stratton, MR
Easton, DF
Huddart, RA
Rahman, N
Turnbull, C
Type
Journal Article
Metadata
Show full item recordAbstract
Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks. So far, six loci associated with TGCT have been reported. From genome-wide association study (GWAS) analysis of 307,291 SNPs in 986 TGCT cases and 4,946 controls, we selected for follow-up 694 SNPs, which we genotyped in a further 1,064 TGCT cases and 10,082 controls from the UK. We identified SNPs at nine new loci (1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3) showing association with TGCT (P < 5 × 10(-8)), which together account for an additional 4-6% of the familial risk of TGCT. The loci include genes plausibly related to TGCT development. PRDM14, at 8q13.3, is essential for early germ cell specification, and DAZL, at 3p24.3, is required for the regulation of germ cell development. Furthermore, PITX1, at 5q31.1, regulates TERT expression and is the third TGCT-associated locus implicated in telomerase regulation.
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Subject
UK Testicular Cancer Collaboration (UKTCC)
Humans
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Genetic Predisposition to Disease
RNA-Binding Proteins
DNA-Binding Proteins
Transcription Factors
Repressor Proteins
Risk Factors
Gene Frequency
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Male
Genome-Wide Association Study
Research team
Predisposition & Translation Genetics
Genetic Susceptibility
Sarcoma Molecular Pathology
Clinical Academic Radiotherapy (Huddart)
Oncogenetics
Language
eng
Date accepted
2013-04-10
License start date
2013-06
Citation
Nature genetics, 2013, 45 (6), pp. 686 - 689
Publisher
NATURE PUBLISHING GROUP