Common Variation at 2q22.3 (ZEB2) Influences the Risk of Renal Cancer

Overview

Journal Hum Mol Genet

Specialties Genetics
Molecular Biology

Date 2012 Nov 28

PMID 23184150

Citations 34

Authors

Marc Henrion

Matthew Frampton

Ghislaine Scelo

Mark Purdue

Yuanqing Ye

Peter Broderick

Alastair Ritchie

Richard Kaplan

Angela Meade

James McKay

Mattias Johansson

Mark Lathrop

James Larkin

Nathaniel Rothman

Zhaoming Wang

Wong-Ho Chow

Victoria L Stevens

W Ryan Diver

Susan M Gapstur

Demetrius Albanes

Jarmo Virtamo

Xifeng Wu

Paul Brennan

Stephen Chanock

Timothy Eisen

Richard S Houlston

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Purdue M, Dutta D, Machiela M, Gorman B, Winter T, Okuhara D Nat Genet. 2024; 56(5):809-818.

PMID: 38671320 DOI: 10.1038/s41588-024-01725-7.

Cyclin dependent kinase inhibitor 3 (CDKN3) upregulation is associated with unfavorable prognosis in clear cell renal cell carcinoma and shapes tumor immune microenvironment: A bioinformatics analysis.

Al Sharie A, Abu Zahra A, El-Elimat T, Darweesh R, Al-Khaldi A, Abu Mousa B Medicine (Baltimore). 2023; 102(36):e35004.

PMID: 37682177 PMC: 10489202. DOI: 10.1097/MD.0000000000035004.

The current state of genetic risk models for the development of kidney cancer: a review and validation.

Harrison H, Li N, Saunders C, Rossi S, Dennis J, Griffin S BJU Int. 2022; 130(5):550-561.

PMID: 35460182 PMC: 9790357. DOI: 10.1111/bju.15752.

Altered regulation of DPF3, a member of the SWI/SNF complexes, underlies the 14q24 renal cancer susceptibility locus.

Colli L, Jessop L, Myers T, Camp S, Machiela M, Choi J Am J Hum Genet. 2021; 108(9):1590-1610.

PMID: 34390653 PMC: 8456159. DOI: 10.1016/j.ajhg.2021.07.009.

8q24 clear cell renal cell carcinoma germline variant is associated with VHL mutation status and clinical aggressiveness.

Eckel-Passow J, Yan H, Kosel M, Serie D, Decker P, Jenkins R BMC Urol. 2020; 20(1):173.

PMID: 33121461 PMC: 7597051. DOI: 10.1186/s12894-020-00745-9.

References

Broderick P, Chubb D, Johnson D, Weinhold N, Forsti A, Lloyd A . Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk. Nat Genet. 2011; 44(1):58-61. PMC: 5108406. DOI: 10.1038/ng.993. View

Han S, Yeager M, Moore L, Wei M, Pfeiffer R, Toure O . The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma. Hum Mol Genet. 2011; 21(5):1190-200. PMC: 3277315. DOI: 10.1093/hmg/ddr551. View

Wu X, Scelo G, Purdue M, Rothman N, Johansson M, Ye Y . A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23. Hum Mol Genet. 2011; 21(2):456-62. PMC: 3276284. DOI: 10.1093/hmg/ddr479. View

Chow W, Dong L, Devesa S . Epidemiology and risk factors for kidney cancer. Nat Rev Urol. 2010; 7(5):245-57. PMC: 3012455. DOI: 10.1038/nrurol.2010.46. View

Houlston R, Ford D . Genetics of coeliac disease. QJM. 1996; 89(10):737-43. DOI: 10.1093/qjmed/89.10.737. View

Broderick P, Wang Y, Vijayakrishnan J, Matakidou A, Spitz M, Eisen T . Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Res. 2009; 69(16):6633-41. PMC: 2754318. DOI: 10.1158/0008-5472.CAN-09-0680. View

Dimas A, Deutsch S, Stranger B, Montgomery S, Borel C, Attar-Cohen H . Common regulatory variation impacts gene expression in a cell type-dependent manner. Science. 2009; 325(5945):1246-50. PMC: 2867218. DOI: 10.1126/science.1174148. View

Goldgar D, Easton D, Cannon-Albright L, Skolnick M . Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst. 1994; 86(21):1600-8. DOI: 10.1093/jnci/86.21.1600. View

Linehan W, Pinto P, Bratslavsky G, Pfaffenroth E, Merino M, Vocke C . Hereditary kidney cancer: unique opportunity for disease-based therapy. Cancer. 2009; 115(10 Suppl):2252-61. PMC: 2720093. DOI: 10.1002/cncr.24230. View

10.

Stranger B, Montgomery S, Dimas A, Parts L, Stegle O, Ingle C . Patterns of cis regulatory variation in diverse human populations. PLoS Genet. 2012; 8(4):e1002639. PMC: 3330104. DOI: 10.1371/journal.pgen.1002639. View

11.

Krishnamachary B, Zagzag D, Nagasawa H, Rainey K, Okuyama H, Baek J . Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Res. 2006; 66(5):2725-31. DOI: 10.1158/0008-5472.CAN-05-3719. View

12.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

13.

Dobbins S, Broderick P, Melin B, Feychting M, Johansen C, Andersson U . Common variation at 10p12.31 near MLLT10 influences meningioma risk. Nat Genet. 2011; 43(9):825-7. PMC: 5053355. DOI: 10.1038/ng.879. View

14.

Shete S, Lau C, Houlston R, Claus E, Barnholtz-Sloan J, Lai R . Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium. Cancer Res. 2011; 71(24):7568-75. PMC: 3242820. DOI: 10.1158/0008-5472.CAN-11-0013. View

15.

Nica A, Parts L, Glass D, Nisbet J, Barrett A, Sekowska M . The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet. 2011; 7(2):e1002003. PMC: 3033383. DOI: 10.1371/journal.pgen.1002003. View

16.

Gabriel S, Schaffner S, Nguyen H, Moore J, Roy J, Blumenstiel B . The structure of haplotype blocks in the human genome. Science. 2002; 296(5576):2225-9. DOI: 10.1126/science.1069424. View

17.

Yeager M, Orr N, Hayes R, Jacobs K, Kraft P, Wacholder S . Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007; 39(5):645-9. DOI: 10.1038/ng2022. View

18.

Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2011; 127(12):2893-917. DOI: 10.1002/ijc.25516. View

19.

Verstappen G, van Grunsven L, Michiels C, van de Putte T, Souopgui J, Van Damme J . Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex. Hum Mol Genet. 2008; 17(8):1175-83. DOI: 10.1093/hmg/ddn007. View

20.

Purdue M, Johansson M, Zelenika D, Toro J, Scelo G, Moore L . Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nat Genet. 2010; 43(1):60-5. PMC: 3049257. DOI: 10.1038/ng.723. View