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Meta-Analysis
. 2013 Jun;45(6):686-9.
doi: 10.1038/ng.2635. Epub 2013 May 12.

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

Elise Ruark  1 , Sheila Seal, Heather McDonald, Feng Zhang, Anna Elliot, Kingwai Lau, Elizabeth Perdeaux, Elizabeth Rapley, Rosalind Eeles, Julian Peto, Zsofia Kote-Jarai, Kenneth Muir, Jeremie Nsengimana, Janet Shipley; UK Testicular Cancer Collaboration (UKTCC); D Timothy Bishop, Michael R Stratton, Douglas F Easton, Robert A Huddart, Nazneen Rahman, Clare Turnbull
Affiliations
Meta-Analysis

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

Elise Ruark et al. Nat Genet. 2013 Jun.

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.

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Figures

Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
Figure 1
Figure 1. Regional plots of the nine new TGCT loci (a–i)
Plots show the genomic regions of association with TGCT on chromosome (a), 1q22 (b) 1q24.1, (c) 3p24.3, (d) 4q24, (e) 5q31.1, (f) 8q13.3, (g) 16q12.1, (h) 17q22 and (i) 21q22.3. Shown by diamonds are the −log10 association P values of SNPs in 986 cases and 4,946 controls from the GWAS, combined with 1,064 cases of TGCT and 10,082 controls from the iCOGs replication. Shown by squares are SNPs genotyped in the GWAS alone. The intensity of red shading indicates the strength of LD with the index SNP (labeled). Also shown are the SNP build 36 coordinates in kilobases (kb), recombination rates in centimorgans (cM) per megabase (Mb) (in blue) and the genes in the region (in green).
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References

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