Oligogenic segregation analysis of hereditary prostate cancer pedigrees: Evidence for multiple loci affecting age at onset

Erin M. Conlon, Ellen L. Goode, Mark Gibbs, Janet L. Stanford, Michael Badzioch, Marta Janer, Suzanne Kolb, Lee Hood, Elain A. Ostrander, Gail P. Jarvik, Ellen M. Wijsman

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23 Scopus citations

Abstract

Previous studies have suggested strong evidence for a hereditary component to prostate cancer (PC) susceptibility. Here, we analyze 3,796 individuals in 263 PC families recruited as part of the ongoing Prostate Cancer Genetic Research Study (PROGRESS). We use Markov chain Monte Carlo (MCMC) oligogenic segregation analysis to estimate the number of quantitative trait loci (QTLs) and their contribution to the variance in age at onset of hereditary PC (HPC). We estimate 2 covariate effects: diagnosis of PC before and after prostate-specific antigen (PSA) test availability, and presence/absence of at least 1 blood relative with primary neuroepithelial brain cancer (BC). We find evidence that 2 to 3 QTLs contribute to the variance in age at onset of HPC. The 2 QTLs with the largest contribution to the total variance are both effectively dominant loci. We find that the covariate for diagnosis before and after PSA test availability is important. Our findings for the number of QTLs contributing to HPC and the variance contribution of these QTLs will be instructive in mapping and identifying these genes.

Original languageEnglish (US)
Pages (from-to)630-635
Number of pages6
JournalInternational Journal of Cancer
Volume105
Issue number5
DOIs
StatePublished - Jul 10 2003

Keywords

  • Ascertainment
  • Bayesian
  • Genetic heterogeneity
  • Markov chain Monte Carlo
  • Quantitative traits

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Conlon, E. M., Goode, E. L., Gibbs, M., Stanford, J. L., Badzioch, M., Janer, M., Kolb, S., Hood, L., Ostrander, E. A., Jarvik, G. P., & Wijsman, E. M. (2003). Oligogenic segregation analysis of hereditary prostate cancer pedigrees: Evidence for multiple loci affecting age at onset. International Journal of Cancer, 105(5), 630-635. https://doi.org/10.1002/ijc.11128