Combined genome-wide scan for prostate cancer susceptibility genes

Elizabeth M. Gillanders, Jianfeng Xu, Bao Li Chang, Ethan M. Lange, Fredrik Wiklund, Joan E. Bailey-Wilson, Agnes Baffoe-Bonnie, Mary Pat Jones, Derek Gildea, Erica Riedesel, Julie Albertus, Sarah D. Isaacs, Kathleen E. Wiley, Caroline E. Mohai, Mika P. Matikainen, Teuvo L.J. Tammela, S. Lilly Zheng, W. Mark Brown, Annika Rökman, John D. CarptenDeborah A. Meyers, Patrick C. Walsh, Johanna Schleutker, Henrik Gronberg, Kathleen A. Cooney, William B. Isaacs, Jeffrey M. Trent

Research output: Contribution to journalArticlepeer-review


Background: Prostate cancer represents a substantial public health burden worldwide. It is the second leading cause of cancer death among men in the United States. A family history of the disease is among the most well-established risk factors for prostate cancer. Efforts to localize prostate cancer susceptibility alleles by using genetic linkage analysis methods have been hindered by genetic heterogeneity, incomplete penetrance, disease phenocopies, and the lack of DNA samples from parents of individuals with late-onset prostate cancer. Methods: We performed a combined genome-wide linkage analysis among 426 families from four existing hereditary prostate cancer (HPC) study populations to systematically search for prostate cancer susceptibility genes. To decrease the degree of locus heterogeneity, we analyzed subsets of families with similar clinical and demographic characteristics. Nonparametric multipoint linkage was the primary method of analysis. Results are presented as allele-sharing logarithm of the odds (LOD) scores, and all reported P values are two-sided. Results: The strongest evidence for prostate cancer linkage was found at chromosome region 17q22 (nonparametric multipoint Kong and Cox allele-sharing LOD score = 3.16 at marker D17S787; P = .00007). Stratified analyses revealed several additional chromosomal regions that are likely to segregate prostate cancer susceptibility genes among specific subsets of HPC families, including 15q11 among families with late-onset disease (allele-sharing LOD = 5.57 at marker D15S128; P<.00001) and 4q35 among families with four or more affected family members (allele-sharing LOD = 3.10 at marker D4S1615; P = .00008). Conclusion: Fine mapping studies to facilitate identification of prostate cancer susceptibility genes in these linked regions are warranted.

Original languageEnglish (US)
Pages (from-to)1240-1247
Number of pages8
JournalJournal of the National Cancer Institute
Issue number16
StatePublished - Aug 18 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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