title: 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.
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.
authors.affiliation: Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Cropp
authors.forename: Claire L
authors.initials: CL
authors.lastname: Simpson
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.forename: Nati
authors.initials: N
authors.lastname: Ha
authors.forename: Asha
authors.initials: A
authors.lastname: George
authors.forename: MaryPat S
authors.initials: MS
authors.lastname: Jones
authors.forename: Ursula
authors.initials: U
authors.lastname: Harper
authors.forename: Damaris
authors.initials: D
authors.lastname: Ponciano-Jackson
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Green
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Joan
authors.initials: J
authors.lastname: Bailey-Wilson
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
mesh_terms: D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002889:Chromosomes, Human, Pair 2; D005387:Finland; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D011471:Prostatic Neoplasms / Q000235:genetics*