Linkage analysis of 49 high-risk families does not support a common familial prostate cancer-susceptibility gene at 1q24-25

Richard A. McIndoe, Janet L. Stanford, Mark Gibbs, Gail P. Jarvik, Susan Brandzel, Cassandra L. Neal, Sarah Li, Jason T. Gammack, Allen A. Gay, Ellen L. Goode, Leroy Hood, Elaine A. Ostrander

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104 Scopus citations

Abstract

Linkage of a putative prostate cancer-susceptibility locus (HPC1) to chromosome 1q24-25 has recently been reported. Confirmation of this linkage in independent data sets is essential because of the complex nature of this disease. Here we report the results of a linkage analysis using 10 polymorphic markers spanning ~37 cM in the region of the putative HPC1 locus in 49 high-risk prostate cancer families. Data were analyzed by use of two parametric models and a nonparametric method. For the parametric LOD-score method, the first model was identical to the original report by Smith and co- workers ('Hopkins'), and the second was based on a segregation analysis previously reported by Carter and coworkers ('Seattle'). In both cases, our results do not confirm the linkage reported for this region. Calculated LOD scores from the two-point analysis for each marker were highly negative at small recombination fractions. Multipoint LOD scores for this linkage group were also highly negative. Additionally, we were unable to demonstrate heterogeneity within the data set, using HOMOG. Although these data do not formally exclude linkage of a prostate cancer-susceptibility locus at HPC1, it is likely that other prostate cancer-susceptibility loci play a more critical role in the families that we studied.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalAmerican journal of human genetics
Volume61
Issue number2
DOIs
StatePublished - Aug 1997
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    McIndoe, R. A., Stanford, J. L., Gibbs, M., Jarvik, G. P., Brandzel, S., Neal, C. L., Li, S., Gammack, J. T., Gay, A. A., Goode, E. L., Hood, L., & Ostrander, E. A. (1997). Linkage analysis of 49 high-risk families does not support a common familial prostate cancer-susceptibility gene at 1q24-25. American journal of human genetics, 61(2), 347-353. https://doi.org/10.1086/514853