Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.

Ruark, Elise; Seal, Sheila; McDonald, Heather; Zhang, Feng; Elliot, Anna; Lau, Kingwai; Perdeaux, Elizabeth; Rapley, Elizabeth; Eeles, Rosalind; Peto, Julian; +11 more... Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Shipley, Janet; UK Testicular Cancer Collaboration (UKTCC); Bishop, D Timothy; Stratton, Michael R; Easton, Douglas F; Huddart, Robert A; Rahman, Nazneen; Turnbull, Clare; (2013) Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14. Nature genetics, 45 (6). pp. 686-689. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.2635

Abstract

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.

Additional Information

Item Type	Article
Keywords	genome-wide association, germ-cell lineage, tert-clptm1l locus, autosomal gene, breast-cancer, mice, protein, testis, tumor, tex14
Faculty and Department	Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID	23666240
ISI	319563900018
Related URLs	OA Location