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

Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks(1,2). To date, six loci associated with TGCT have been reported(3-7). From GWAS analysis of 307,291 SNPs in 986 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 showing association with TGCT (P<5×10(−8)), at 1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3, 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(8) whilst DAZL, at 3p24.3, is required for regulation of germ cell development(9). Furthermore, PITX1, at 5q31.1 regulates TERT expression, and is the third TGCT locus implicated in telomerase regulation(10).