Linkage analysis of prostate cancer susceptibility: confirmation of linkage at 8p22-23

Frequent loss of heterogeneity in prostate cancer cells and linkage studies of families affected by hereditary prostate cancer (HPC) have implied that the short arm of chromosome 8, specifically 8p22-23, may harbor a prostate-cancer-susceptibility gene. In a recent study, seven potentially important...

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Bibliographic Details
Published in:Human genetics 2003-04, Vol.112 (4), p.414-418
Main Authors: WIKLUND, Fredrik, JONSSON, Björn-Anders, GÖRANSSON, Ingela, BERGH, Anders, GRÖNBERG, Henrik
Format: Article
Language:English
Subjects:
Age of Onset
Aged
Biological and medical sciences
Cancer
Chromosomes, Human, Pair 8 - genetics
Disease susceptibility
Fundamental and applied biological sciences. Psychology
Genes. Genome
Genetic aspects
Genetic Linkage
Genetic Predisposition to Disease
Humans
Lod Score
Male
Middle Aged
Molecular and cellular biology
Molecular genetics
Mutation
Oncology, Experimental
Prostate cancer
Prostatic Neoplasms - genetics
Receptors, Immunologic - genetics
Receptors, Scavenger
Scavenger Receptors, Class A
Sweden
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Summary:Frequent loss of heterogeneity in prostate cancer cells and linkage studies of families affected by hereditary prostate cancer (HPC) have implied that the short arm of chromosome 8, specifically 8p22-23, may harbor a prostate-cancer-susceptibility gene. In a recent study, seven potentially important mutations in the macrophage scavenger receptor 1 gene (MSR1), located at 8p22, were observed in families affected with HPC, and an indication of co-segregation between these mutations and prostate cancer was reported. In an attempt to confirm linkage at 8p22-23, we performed linkage analyses in 57 families affected with HPC (ascertained throughout Sweden) by using 13 markers on the short arm of chromosome 8. In the complete set of families, evidence for prostate cancer linkage was observed at 8p22-23, with a peak hold of 1.08 (P=0.03), observed at D8S1731, approximately 1 cM centromeric to the MSR1 gene. At marker D8S1135, the closest marker to MSR1, a hlod of 1.07 (P=0.03) was observed. Evidence of linkage was seen in families with early-onset HPC and in families with a small number of affected individuals. The peak multipoint non-parametric linkage score was 2.01 (P=0.03) at D8S552 in the 14 pedigrees with mean age at onset
ISSN:0340-6717
1432-1203
1432-1203
DOI:10.1007/s00439-003-0916-6