Publication Date:
2012-06-20
Description:
Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidationof the genetic etiology of prostate cancer is difficult because of incomplete penetrance andgenetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage toprostate cancer has been found on several chromosomes including the X; however,identification of causative genes has been elusive. Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellitemarkers in each of 11 groups of multiple-case prostate cancer families from the InternationalConsortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant familyspecificlinkage statistics across the entire 1,323 families and in several predefined subsetswere then performed. Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score(HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 yearsexhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset offamilies with only 2-3 affected men and some evidence of male-to-male transmission ofprostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM).For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when familiesused in the original published report of linkage to Xq27-28 were excluded. Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete setof families, the subset of families with earlier age at onset exhibited more evidence of linkagethan families with later onset of disease. A subset of families with 2-3 affected individualsand with some evidence of male to male disease transmission showed stronger linkagesignals. Our results suggest that the genetic basis for prostate cancer in our families is muchmore complex than a single susceptibility locus on the X chromosome, and that futureexplorations of the Xq27-28 region should focus on the subset of families identified here withthe strongest evidence of linkage to this region.
Electronic ISSN:
1471-2350
Topics:
Biology
,
Medicine
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