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Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour
  1. Christian P Kratz1,
  2. Summer S Han1,
  3. Philip S Rosenberg1,
  4. Sonja I Berndt1,
  5. Laurie Burdett2,
  6. Meredith Yeager2,
  7. Larissa A Korde1,
  8. Phuong L Mai1,
  9. Ruth Pfeiffer1,
  10. Mark H Greene1
  1. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
  2. 2Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, Gaithersburg, Maryland, USA
  1. Correspondence to Christian P Kratz, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Blvd, EPS/7018, Rockville, MD 20852, USA; kratzcp{at}


Background Familial testicular germ cell tumours (TGCTs) and bilateral TGCTs comprise 1–2% and 5% of all TGCTs, respectively, but their genetic basis remains largely unknown.

Aim To investigate the contribution of known testicular cancer risk variants in familial and bilateral TGCTs.

Methods and results The study genotyped 106 single nucleotide polymorphisms (SNPs) in four regions (BAK1, DMRT1, KITLG, TERT-CLPTM1L) previously identified from genome-wide association studies of TGCT, including risk single nucleotide polymorphisms (SNPs) rs210138 (BAK1), rs755383 (DMRT1), rs4635969 (TERT-CLPTM1L) in 97 cases with familial TGCT and 22 affected individuals with sporadic bilateral TGCT as well as 871 controls. Using a generalised estimating equations method that takes into account blood relationships among cases, the associations with familial and bilateral TGCT were analysed. Three previously identified risk SNPs were found to be associated with familial and bilateral TGCT (rs210138: OR 1.80, CI 1.35 to 2.41, p=7.03×10−5; rs755383: OR 1.67, CI 1.23 to 2.22, p=6.70×10−4; rs4635969: OR 1.59, CI 1.16 to 2.19, p=4.07×10−3). Evidence for a second independent association was found for an SNP in TERT (rs4975605: OR 1.68, CI 1.23 to 2.29, p=1.24×10−3). Another association with an SNP was identified in KITLG (rs2046971: OR 2.33, p=1.28×10−3); this SNP is in high linkage disequilibrium (LD) with reported risk variant rs995030.

Conclusion This study provides evidence for replication of recent genome-wide association studies results and shows that variants in or near BAK1, DMRT1, TERT-CLPTM1L, and KITLG predispose to familial and bilateral TGCT. These findings imply that familial TGCT and sporadic TGCT share a common genetic basis.

  • Testicular cancer
  • cancer-prone syndromes
  • risk variants
  • paediatric oncology
  • genetic epidemiology
  • genetics
  • genome-wide

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  • CPK and SSH contributed equally to this work.

  • Funding This work was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute, and by a support services contract with Westat (N02-CP-65504).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by NCI IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.