title: Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour.
abstract: 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.
  
  
  OBJECTIVE
  To investigate the contribution of known testicular cancer risk variants in familial and bilateral TGCTs.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of CancerEpidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852, USA. kratzcp@mail.nih.gov
authors: Christian P
authors: CP
authors: Kratz
authors: Summer S
authors: SS
authors: Han
authors: Philip S
authors: PS
authors: Rosenberg
authors: Sonja I
authors: SI
authors: Berndt
authors: Laurie
authors: L
authors: Burdett
authors: Meredith
authors: M
authors: Yeager
authors: Larissa A
authors: LA
authors: Korde
authors: Phuong L
authors: PL
authors: Mai
authors: Ruth
authors: R
authors: Pfeiffer
authors: Mark H
authors: MH
authors: Greene
references: Curr Opin Oncol. 2010 May;22(3):236-41
references: 20401976
references: Public Health. 2008 Sep;122(9):862-72
references: 18555499
references: Nat Genet. 2010 Jul;42(7):604-7
references: 20543847
references: Br J Cancer. 2008 Jan 15;98(1):171-3
references: 18071360
references: Br J Cancer. 2004 May 4;90(9):1765-70
references: 15208620
references: J Natl Cancer Inst. 2005 Jul 20;97(14):1056-66
references: 16030303
references: Nat Genet. 2000 Feb;24(2):197-200
references: 10655070
references: Nat Genet. 2009 Jul;41(7):811-5
references: 19483682
references: Control Clin Trials. 2000 Dec;21(6 Suppl):273S-309S
references: 11189684
references: Br J Cancer. 2008 Nov 18;99(10):1748-53
references: 18841155
references: Cancer. 1997 Nov 15;80(10):1954-60
references: 9366298
references: Am J Hum Genet. 2004 Jan;74(1):106-20
references: 14681826
references: Eur J Cancer. 1997 Feb;33(2):244-52
references: 9135496
references: Int J Cancer. 2001 Apr 1;92(1):144-50
references: 11279618
references: Bioinformatics. 2005 Jan 15;21(2):263-5
references: 15297300
references: Endocr Relat Cancer. 2010 Mar 08;17(2):R109-21
references: 20228134
references: Nat Genet. 2009 Jul;41(7):807-10
references: 19483681
references: Hum Mol Genet. 2006 Feb 1;15(3):443-51
references: 16407372
references: Genet Epidemiol. 2009 Dec;33(8):700-9
references: 19333968
references: Lancet. 1997 Dec 13;350(9093):1723-8
references: 9413462