Original Article

Common variants in 8q24 are associated with risk for prostate cancer and tumor aggressiveness in men of European ancestry

  1. Prodipto Pal1,
  2. Huifeng Xi1,
  3. Saurav Guha1,
  4. Guangyun Sun1,
  5. Brian T. Helfand2,
  6. Joshua J. Meeks2,
  7. Brian K. Suarez3,
  8. William J. Catalona2,
  9. Ranjan Deka1,*

Article first published online: 26 JUN 2009

DOI: 10.1002/pros.20999

Issue

The Prostate

The Prostate

Volume 69, Issue 14, pages 1548–1556, 1 October 2009

Additional Information

How to Cite

Pal, P., Xi, H., Guha, S., Sun, G., Helfand, B. T., Meeks, J. J., Suarez, B. K., Catalona, W. J. and Deka, R. (2009), Common variants in 8q24 are associated with risk for prostate cancer and tumor aggressiveness in men of European ancestry. The Prostate, 69: 1548–1556. doi: 10.1002/pros.20999

Author Information

  1. 1

    Department of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center, Cincinnati, Ohio

  2. 2

    Department of Urology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

  3. 3

    Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri

*Department of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center, 3223 Eden Avenue, Cincinnati, OH 45267-0056.

Publication History

  1. Issue published online: 24 AUG 2009
  2. Article first published online: 26 JUN 2009
  3. Manuscript Accepted: 18 MAY 2009
  4. Manuscript Received: 6 MAR 2009

Funded by

  • Urological Research Foundation. Grant Number: P50 CA90386-05S2
  • Robert H. Lurie Comprehensive Cancer Center. Grant Number: P30 CA60553

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Keywords:

  • genetic susceptibility;
  • association study;
  • tagging SNPs;
  • chromosome 8q24;
  • MYC proto-oncogene

Abstract

BACKGROUND

Recent whole genome association studies have independently identified multiple prostate cancer (PC) risk variants on 8q24. We have evaluated association of common variants in this region with PC susceptibility and tumor aggressiveness in a sample of European American men.

METHODS

Forty-nine tagging SNPs including three previously reported significant variants (rs1447295, rs6983267, rs16901979) and seven variants in the 5′ upstream region of the MYC proto-oncogene were tested for association with susceptibility to PC and tumor aggressiveness in 596 histologically verified PC cases and 567 ethnically matched controls.

RESULTS

Significant associations with susceptibility to PC were found at 17 SNPs, four of which (rs1016342, rs1378897, rs871135, and rs6470517) remained significant after adjusting for multiple corrections. One of the associated SNPs, rs871135, is located in the putative gene POU5F1P1 within the 8q24 region. An in slico analysis showed that the associated variant of this SNP alters a transcription factor implicating a plausible regulatory role. Additionally, one of the significantly associated SNPs, rs6470517, with PC susceptibility showed a significant over-representation of the G allele in cases with aggressive tumor.

CONCLUSIONS

Although this study does not directly confirm associations of the three specific SNPs (cited above), it corroborates reported signals of association in 8q24 reaffirming that genetic variation on 8q24 influences susceptibility to PC in men of European ancestry. Although our study did not confirm the allelic association of rs1447295, meta-analysis of this SNP provided support to previous reported associations. Further, this study implicates the 8q24 region with aggressive forms of PC. Prostate 69: 1548–1556, 2009. © 2009 Wiley-Liss, Inc.

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