Genome-Wide Scan of Brothers: Replication and Fine Mapping of Prostate Cancer Susceptibility and Aggressiveness Loci

John S. Witte*, Brian K. Suarez, Bonnie Thiel, Jennifer Lin, Adong Yu, Tarit K. Banerjee, James K. Burmester, Graham Casey, William J. Catalona

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

BACKGROUND. Substantial evidence suggests that genetic factors play an important role in both the risk of prostate cancer and its biologic aggressiveness. Here we investigate prostate cancer susceptibility and aggressiveness with genome-wide linkage analyses of affected brothers. METHODS. We first undertook a new genome-wide linkage study of 259 brothers with prostate cancer. Our analyses tested whether the proportion of marker alleles shared by brothers was correlated with disease status or Gleason score. To further clarify 11 linkage regions observed here or previously, we genotyped and analyzed an additional 101 finely spaced markers in the 259 men, and in 594 previously studied brothers, allowing for a pooled genome-wide analysis of 853 affected brothers. RESULTS. In the new study, we detected linkage to prostate cancer on chromosome 16q23 (P = 0.009), replicating previous results, and to chromosome 11q24 (P = 0.001). In the pooled analysis, the 16q23 linkage was strengthened (P = 0.0005), as was our previous linkage to chromosome 16p (P = 0.0001), and we detected linkage to chromosome 2q32 (P = 0.009). When evaluating Gleason score, our new study detected linkage to chromosome 7q32 (P = 0.0009), again replicating previous results, and to chromosomes 5p15 (P = 0.003), 9q34 (P = 0.009), 10q26 (P = 0.03), and 18p11 (P = 0.02). In the pooled analysis of Gleason score, we observed stronger linkage to chromosome 7q32 (P = 0.0002), but slightly weaker linkage to chromosomes 5q33 (P = 0.005) and 19q13 (P = 0.009) than previously reported. In addition, the new linkages to chromosomes 10q26 and 18p11 were strengthened (P = 0.0002 and P = 0.002, respectively). CONCLUSIONS. Our results provide compelling evidence for loci harboring prostate cancer susceptibility and tumor aggressiveness genes, especially on chromosomes 16q23 and 7q32.

Original languageEnglish (US)
Pages (from-to)298-308
Number of pages11
JournalProstate
Volume57
Issue number4
DOIs
StatePublished - Dec 1 2003

Keywords

  • Affected siblings
  • Carcinogenesis
  • Linkage
  • Prostate cancer genetics
  • Urology

ASJC Scopus subject areas

  • Oncology
  • Urology

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