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Open Access Research article

Meta-analysis of 8q24 for seven cancers reveals a locus between NOV and ENPP2 associated with cancer development

Abra G Brisbin1, Yan W Asmann1, Honglin Song2, Ya-Yu Tsai3, Jeremiah A Aakre1, Ping Yang1, Robert B Jenkins4, Paul Pharoah2, Fredrick Schumacher5, David V Conti5, David J Duggan6, Mark Jenkins7, John Hopper7, Steven Gallinger8, Polly Newcomb9, Graham Casey5, Thomas A Sellers3 and Brooke L Fridley1*

Author Affiliations

1 Department of Health Sciences Research, Mayo Clinic, Rochester, USA

2 Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK

3 Department of Cancer Genetics and Epidemiology, Risk Assessment, Detection, and Intervention Program, Moffitt Cancer Center, Tampa, USA

4 Division of Experimental Pathology, Mayo Clinic, Rochester, USA

5 Department of Preventive Medicine, University of Southern California, Los Angeles, USA

6 Translational Genomics Research Institute, Phoenix, USA

7 School of Population Health, University of Melbourne, Victoria, Australia

8 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

9 Fred Hutchinson Cancer Research Center, Seattle, USA

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BMC Medical Genetics 2011, 12:156  doi:10.1186/1471-2350-12-156

Published: 5 December 2011

Abstract

Background

Human chromosomal region 8q24 contains several genes which could be functionally related to cancer, including the proto-oncogene c-MYC. However, the abundance of associations around 128 Mb on chromosome 8 could mask the appearance of a weaker, but important, association elsewhere on 8q24.

Methods

In this study, we completed a meta-analysis of results from nine genome-wide association studies for seven types of solid-tumor cancers (breast, prostate, pancreatic, lung, ovarian, colon, and glioma) to identify additional associations that were not apparent in any individual study.

Results

Fifteen SNPs in the 8q24 region had meta-analysis p-values < 1E-04. In particular, the region consisting of 120,576,000-120,627,000 bp contained 7 SNPs with p-values < 1.0E-4, including rs6993464 (p = 1.25E-07). This association lies in the region between two genes, NOV and ENPP2, which have been shown to play a role in tumor development and motility. An additional region consisting of 5 markers from 128,478,000 bp - 128,524,000 (around gene POU5F1B) had p-values < 1E-04, including rs6983267, which had the smallest p-value (p = 6.34E-08). This result replicates previous reports of association between rs6983267 and prostate and colon cancer.

Conclusions

Further research in this area is warranted as these results demonstrate that the chromosomal region 8q24 may contain a locus that influences general cancer susceptibility between 120,576 and 120,630 kb.