Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer
Marc Henrion
(1)
,
Matthew Frampton
(1)
,
Ghislaine Scelo
(2)
,
Mark Purdue
(3)
,
Yuanqing Ye
(4)
,
Peter Broderick
(1)
,
Alastair Ritchie
(5)
,
Richard Kaplan
(5)
,
Angela Meade
(5)
,
James Mckay
(6)
,
Mattias Johansson
(6)
,
Mark Lathrop
(7, 8)
,
James Larkin
(9)
,
Nathaniel Rothman
(3)
,
Zhaoming Wang
(3, 10)
,
Wong-Ho Chow
(3, 4)
,
Victoria Stevens
(11)
,
W. Ryan Diver
(12)
,
Susan Gapstur
(12)
,
Demetrius Albanes
(3)
,
Jarmo Virtamo
(13)
,
Xifeng Wu
(4)
,
Paul Brennan
(2)
,
Stephen Chanock
(3)
,
Timothy Eisen
(14)
,
Richard Houlston
(15)
1
Institute of Cancer Research [Surrey, UK]
2 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
3 NCI-NIH - National Cancer Institute [Bethesda]
4 The University of Texas M.D. Anderson Cancer Center [Houston]
5 MRC CTU - Medical Research Council Clinical Trials Unit
6 IACR - International Agency for Cancer Research
7 U946 - Variabilité Génétique et Maladies Humaines
8 CNG - Centre National de Génotypage
9 NHS Foundation Trust [London]
10 National Cancer Institute Frederick
11 Division of Geological and Planetary Sciences [Pasadena]
12 American Cancer Society [Atlanta, GA, USA]
13 National Institute for Health and Welfare [Helsinki]
14 CUHP - Cambridge University Health Partners
15 The institute of cancer research [London]
2 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
3 NCI-NIH - National Cancer Institute [Bethesda]
4 The University of Texas M.D. Anderson Cancer Center [Houston]
5 MRC CTU - Medical Research Council Clinical Trials Unit
6 IACR - International Agency for Cancer Research
7 U946 - Variabilité Génétique et Maladies Humaines
8 CNG - Centre National de Génotypage
9 NHS Foundation Trust [London]
10 National Cancer Institute Frederick
11 Division of Geological and Planetary Sciences [Pasadena]
12 American Cancer Society [Atlanta, GA, USA]
13 National Institute for Health and Welfare [Helsinki]
14 CUHP - Cambridge University Health Partners
15 The institute of cancer research [London]
Richard Houlston
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Résumé
Genome-wide association studies (GWASs) of renal cell cancer (RCC) have identified four susceptibility loci thus far. To identify an additional RCC common susceptibility locus, we conducted a GWAS and performed a meta-analysis with published GWASs (totalling 2215 cases and 8566 controls of European background) and followed up the most significant association signals [nine single nucleotide polymorphisms (SNPs) in eight genomic regions] in 3739 cases and 8786 controls. A combined analysis identified a novel susceptibility locus mapping to 2q22.3 marked by rs12105918 (P = 1.80 × 10−8; odds ratio 1.29, 95% CI: 1.18–1.41). The signal localizes to intron 2 of the ZEB2 gene (zinc finger E box-binding homeobox 2). Our findings suggest that genetic variation in ZEB2 influences the risk of RCC. This finding provides further insights into the genetic and biological basis of inherited genetic susceptibility to RCC.