Identification of Nine New Susceptibility Loci for Testicular Cancer, Including Variants Near DAZL and PRDM14

Overview

Journal Nat Genet

Specialty Genetics

Date 2013 May 14

PMID 23666240

Citations 90

Authors

Elise Ruark

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

D Timothy Bishop

Michael R Stratton

Douglas F Easton

Robert A Huddart

Nazneen Rahman

Clare Turnbull

Affiliations

Soon will be listed here.

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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