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Nat Commun. 2015 Oct 27;6:8690. doi: 10.1038/ncomms9690.

Identification of four new susceptibility loci for testicular germ cell tumour.

Author information

1
Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK.
2
Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds LS9 7TF, UK.
3
Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
4
Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
5
Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
6
Department of Research, Cancer Registry of Norway, 0369 Oslo, Norway.
7
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
8
Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London SM2 5NG, UK.
9
William Harvey Research Institute, Queen Mary University, London EC1M 6BQ, UK.

Abstract

Genome-wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify additional single-nucleotide polymorphisms (SNPs) associated with TGCT, we conducted a multistage GWAS with a combined data set of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P=1.5 × 10(-9)), 11q14.1 (rs7107174, GAB2, P=9.7 × 10(-11)), 16p13.13 (rs4561483, GSPT1, P=1.6 × 10(-8)) and 16q24.2 (rs55637647, ZFPM1, P=3.4 × 10(-9)). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.

PMID:
26503584
PMCID:
PMC4846317
DOI:
10.1038/ncomms9690
[Indexed for MEDLINE]
Free PMC Article

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