Genome-wide association study identifies new prostate cancer susceptibility loci

Fredrick R. Schumacher, Sonja I. Berndt, Afshan Siddiq, Kevin B. Jacobs, Zhaoming Wang, Sara Lindstrom, Victoria L. Stevens, Constance Chen, Alison M. Mondul, Ruth C. Travis, Daniel O. Stram, Rosalind A. Eeles, Douglas F. Easton, Graham Giles, John L. Hopper, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Kenneth Muir, Ali Amin Al OlamaZsofia Kote-Jarai, Michelle Guy, Gianluca Severi, Henrik Grönberg, William B. Isaacs, Robert Karlsson, Fredrik Wiklund, Jianfeng Xu, Naomi E. Allen, Gerald L. Andriole, Aurelio Barricarte, Heiner Boeing, H. Bas Bueno-de-Mesquita, E. David Crawford, W. Ryan Diver, Carlos A. Gonzalez, J. Michael Gaziano, Edward L. Giovannucci, Mattias Johansson, Loic Le Marchand, Jing Ma, Sabina Sieri, Pär Stattin, Meir J. Stampfer, Anne Tjonneland, Paolo Vineis, Jarmo Virtamo, Ulla Vogel, Stephanie J. Weinstein, Meredith Yeager, Michael J. Thun, Laurence N. Kolonel, Brian E. Henderson, Demetrius Albanes, Richard B. Hayes, Heather Spencer Feigelson, Elio Riboli, David J. Hunter, Stephen J. Chanock, Christopher A. Haiman, Peter Kraft

Research output: Contribution to journalArticle

Abstract

Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P = 4.3 × 10 -8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 × 10 -9). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P 5 0.72 and P 5 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.

Original languageEnglish (US)
Article numberddr295
Pages (from-to)3867-3875
Number of pages9
JournalHuman molecular genetics
Volume20
Issue number19
DOIs
StatePublished - Oct 1 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Schumacher, F. R., Berndt, S. I., Siddiq, A., Jacobs, K. B., Wang, Z., Lindstrom, S., Stevens, V. L., Chen, C., Mondul, A. M., Travis, R. C., Stram, D. O., Eeles, R. A., Easton, D. F., Giles, G., Hopper, J. L., Neal, D. E., Hamdy, F. C., Donovan, J. L., Muir, K., ... Kraft, P. (2011). Genome-wide association study identifies new prostate cancer susceptibility loci. Human molecular genetics, 20(19), 3867-3875. [ddr295]. https://doi.org/10.1093/hmg/ddr295