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Genetics

A numbers game

Nature Reviews Cancer volume 8, pages 160–161 (2008)Cite this article

In their two-stage GWAS, Gilles Thomas and colleagues identified four new loci — one on chromosome 7, two on chromosome 10 and one on chromosome 11 — that are associated with an increased risk of developing prostate cancer. The loci on chromosome 10 include microseminoprotein β (MSMB), a proposed biomarker for prostate cancer, and C-terminal binding protein 2 (CTBP2), a transcriptional corepressor that is highly expressed in prostate tissue. The locus on chromosome 7 encodes JAZF1, another transcriptional repressor that is translocated in endometrial cancer.

Rosalind Eeles and colleagues carried out a GWAS of blood samples from a UK population of 1,854 men diagnosed with prostate cancer who were less than 60 years of age or had a familial history of the disease and 1,894 controls with low serum prostate-specific antigen (PSA). In addition, by screening a further 3,268 cases of prostate cancer and 3,366 controls from the UK and Australia, seven novel susceptibility loci were identified on chromosomes 3, 6, 7, 10, 11, 19 and X, with three of the loci containing candidate susceptibility genes encoding MSMB on chromosome 10 (in agreement with Thomas and colleagues), Lemur tyrosine kinase 2 (LMTK2) on chromosome 7 and kallikrein-related peptidase 3 (KLK3) on chromosome 19. Interestingly, they also found a single nucleotide polymorphism (SNP), rs5945619, that lies between NUDT10 and NUDT11 on the X chromosome. Julius Gudmundsson and colleagues also discovered a SNP in this region, rs5945572. They used data from their previously published GWAS on prostate cancer to follow up possible X-linked SNPs and possible variants associated with aggressive disease. The X-linked SNPs might explain why some families show greater risk between brothers rather than between fathers and sons. They also identified a SNP at 2p15 that is strongly associated with more aggressive forms of prostate cancer.

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ORIGINAL RESEARCH PAPERS

  1. Eeles, R. A. et al. Identification of multiple novel prostate cancer susceptability loci by a genome wide association study. Nature Genet. 10 Feb 2008 (doi: 10.1038/ng.90)

    Article  CAS  Google Scholar 

  2. Thomas, G. et al. Multiple novel loci identified in a genome wide association study of prostate cancer. Nature Genet. 10 Feb 2008 (doi: 10.1038/ng.91)

    Article  CAS  Google Scholar 

  3. Gudmundsson, J. et al. Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nature Genet. 10 Feb 2008 (doi: 10.1038/ng.89)

    Article  CAS  Google Scholar 

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Authors
  1. Nicola McCarthy
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McCarthy, N. A numbers game. Nat Rev Cancer 8, 160–161 (2008). https://doi.org/10.1038/nrc2332

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  • DOI: https://doi.org/10.1038/nrc2332

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