Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland.
Genome-wide linkage studies have been used to localize rare and highly penetrant prostate cancer (PRCA) susceptibility genes. Linkage studies performed in different ethnic backgrounds and populations have been somewhat disparate, resulting in multiple, often irreproducible signals because of genetic heterogeneity and high sporadic background of the disease. Our first genome-wide linkage study and subsequent fine-mapping study of Finnish hereditary prostate cancer (HPC) families gave evidence of linkage to one region. Here, we conducted subsequent scans with microsatellites and SNPs in a total of 69 Finnish HPC families. GENEHUNTER-PLUS was used for parametric and non-parametric analyses. Our microsatellite genome-wide linkage study provided evidence of linkage to 17q12-q23, with a heterogeneity LOD (HLOD) score of 3.14 in a total of 54 of the 69 families. Genome-wide SNP analysis of 59 of the 69 families gave a highest HLOD score of 3.32 at 2q37.3 under a dominant high penetrance model and 3.40 at 17q21-q22 under a dominant reduced penetrance model. Analyzing all 69 families by combining microsatellite and SNP maps also yielded HLOD scores of 3.3 in these same two regions. These significant linkage peaks on chromosome 2 and 17 confirm previous linkage evidence of a locus on 17q from other populations and provide a basis for continued research into genetic factors involved in PRCA. Fine-mapping analysis of these regions is ongoing and candidate genes at linked loci are currently under analysis.
Written by:
Cropp CD, Simpson CL, Wahlfors T, Ha N, George A, Jones MS, Harper U, Ponciano-Jackson D, Green TA, Tammela TL, Joan‐Bailey‐Wilson, Schleutker J.
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Reference: Int J Cancer. 2011 Jan 4. Epub ahead of print.
doi: 10.1002/ijc.25906
PubMed Abstract
PMID: 21207418
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