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. 2011 Nov 15;129(10):2400-7.
doi: 10.1002/ijc.25906. Epub 2011 Apr 20.

Genome-wide linkage scan for prostate cancer susceptibility in Finland: evidence for a novel locus on 2q37.3 and confirmation of signal on 17q21-q22

Cheryl D Cropp  1 , Claire L Simpson, Tiina Wahlfors, Nati Ha, Asha George, MaryPat S Jones, Ursula Harper, Damaris Ponciano-Jackson, Tiffany A Green, Teuvo L J Tammela, Joan Bailey-Wilson, Johanna Schleutker
Affiliations

Genome-wide linkage scan for prostate cancer susceptibility in Finland: evidence for a novel locus on 2q37.3 and confirmation of signal on 17q21-q22

Cheryl D Cropp et al. Int J Cancer. .

Abstract

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 nonparametric 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 3.40 at 2q37.3 under a dominant high penetrance model. Analyzing all 69 families by combining microsatellite and SNP maps also yielded HLOD scores of > 3.3 in two regions (2q37.3 and 17q12-q21.3). 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.

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Figures

Figure 1
Figure 1
Whole genome graphical images for linkage results in 69 Finnish prostate cancer families using the combined SNPs and microsatellite data. HLOD linkage results are shown for a) for a high penetrance dominant affected-only model (penetrance specified as 1.0 and 0.001 for genotypes DD/Dd and dd) and b) a reduced penetrance dominant affected-only model (penetrance specified as 0.5 and 0.05 for genotypes DD/Dd and dd) using GENEHUNTER-PLUS.
Figure 2
Figure 2
Individual HLOD plot for chromosome 17 from the linkage analysis results for 69 Finnish prostate cancer families using the combined SNPs and microsatellite data. HLOD linkage result of 3.44 (p=0.0001) is shown for a reduced penetrance dominant affected-only model (penetrance specified as 0.5 and 0.05 for genotypes DD/Dd and dd) using GENEHUNTER-PLUS. The dashed lines denote the 1-LOD drop region.
Figure 3
Figure 3
Individual HLOD plot for chromosome 2 from the linkage analysis results for 69 Finnish prostate cancer families using the combined SNPs and microsatellite data. HLOD linkage result of 3.32 (p=0.0001) is shown for a high penetrance dominant affected-only model (penetrance specified as 1.0 and 0.001 for genotypes DD/Dd and dd) using GENEHUNTER-PLUS. The dashed lines denote the 1-LOD drop region.
See this image and copyright information in PMC

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