Two independent prostate cancer risk-associated loci at 11q13

S. Lilly Zheng, Victoria L. Stevens, Fredrik Wiklund, Sarah D. Isaacs, Jielin Sun, Shelly Smith, Kristen Pruett, Kathleen E. Wiley, Seong Tae Kim, Yi Zhu, Zheng Zhang, Fang Chi Hsu, Aubrey R. Turner, Jan Erik Johansson, Wennuan Liu, Woo Kim Jin, Bao Li Chang, David Duggan, John Carpten, Carmen RodriguezWilliam Isaacs, Henrik Grönberg, Jianfeng Xu

Research output: Contribution to journalArticlepeer-review

Abstract

Single nucleotide polymorphisms (SNP) at 11q13 were recently implicated in prostate cancer risk by two genome-wide association studies and were consistently replicated in multiple study populations. To explore prostate cancer association in the regions flanking these SNPs, we genotyped 31 tagging SNPs in a ∼110 kb region at 11q13 in a Swedish case-control study (Cancer of the Prostate in Sweden), including 2,899 cases and 1,722 controls. We found evidence of prostate cancer association for the previously implicated SNPs including rs10896449, which we termed locus 1. In addition, multiple SNPs on the centromeric side of the region, including rs12418451, were also significantly associated with prostate cancer risk (termed locus 2). The two groups of SNPs were separated by a recombination hotspot. We then evaluated these two representative SNPs in an additional ∼4,000 cases and ∼3,000 controls from three study populations and confirmed both loci at 11q13. In the combined allelic test of all four populations, P = 4.0 × 10-11 for rs10896449 at locus 1 and P = 1.2 × 10-6 for rs12418451 at locus 2, and both remained significant after adjusting for the other locus and study population. The prostate cancer association at these two 11q13 loci was unlikely confounded by prostate-specific antigen (PSA) detection bias because neither SNP was associated with PSA levels in controls. Unlike locus 1, in which no known gene is located, several putative mRNAs are in close proximity to locus 2. Additional confirmation studies at locus 2 and functional studies for both loci are needed to advance our knowledge on the etiology of prostate cancer.

Original languageEnglish (US)
Pages (from-to)1815-1820
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number6
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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