TY - JOUR
T1 - Meta-analysis of 8q24 for seven cancers reveals a locus between NOV and ENPP2 associated with cancer development
AU - Brisbin, Abra G.
AU - Asmann, Yan W.
AU - Song, Honglin
AU - Tsai, Ya Yu
AU - Aakre, Jeremiah A.
AU - Yang, Ping
AU - Jenkins, Robert B.
AU - Pharoah, Paul
AU - Schumacher, Fredrick
AU - Conti, David V.
AU - Duggan, David J.
AU - Jenkins, Mark
AU - Hopper, John
AU - Gallinger, Steven
AU - Newcomb, Polly
AU - Casey, Graham
AU - Sellers, Thomas A.
AU - Fridley, Brooke L.
N1 - Funding Information:
We thank Margaret Wrensch and Paul Decker for access to the association results from the glioma case-control study; Ellen L. Goode, Joellen M. Schildkraut, Steven Narod, and Rebecca Sutphen for contribution of the US ovarian case-control association results; Jonathan Tyrer, Simon Gayther, and Susan Ramus for contribution of the UK ovarian case-control association results; and the Mayo Genotyping Shared Resource for genotyping the never-smokers lung cancer study. We also thank the Cancer Genetic Markers of Susceptibility (CGEMS) project for providing results for the breast, prostate, pancreatic and lung cancer for the 8q24 region via dbGaP. The research was supported by R01 CA114343 (Sellers), P50 CA108961 (Mayo Clinic Brain Tumor SPORE), RC1 NS068222 (Jenkins), R01 CA80127 (Yang), R01 CA84354 (Yang), R21 CA140879 (Fridley), R21 GM86689 (Fridley), the Minnesota Partnership for Biotechnology and Medical Genomics (Fridley), and the Mayo Foundation. Colon cancer data were provided by the Australian Colorectal Cancer Family Registry (U01 CA097735), the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), and the Seattle Colorectal Cancer Family Registry (U01 CA074794). This work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and PIs. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR. The funding bodies did not influence the study design, the collection, analysis, or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication.
PY - 2011/12/5
Y1 - 2011/12/5
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-2350-12-156
DO - 10.1186/1471-2350-12-156
M3 - Article
C2 - 22142333
AN - SCOPUS:82655170601
SN - 1755-8794
VL - 12
JO - BMC Medical Genetics
JF - BMC Medical Genetics
M1 - 156
ER -