A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease.
2000
Several predisposition loci for hereditary prostate cancer (HPC) have
been suggested, including HPC1 at 1q24-q25
(OMIM #601518) and HPCX at Xq27-q28 (OMIM
#300147). Genetically homogeneous populations, such as that of Finland,
and distinct subsets of families may help to minimize the genetic
heterogeneity that complicates the genetic dissection of complex
traits. Here, the role of the HPC1 and
HPCX loci in a series of Finnish prostate cancer
families was studied, especially in subgroups of families defined by
age, number of affected cases, and the mode of disease transmission.
DNA samples were collected from 57 Finnish HPC families with at least
two living prostate cancer patients. Linkage analysis was carried out
with 39 microsatellite markers for the HPC1 region and
22 markers for the HPCX region. The maximum two-point
LOD score for the HPCX was 2.05 (marker DXS1205, atθ
= 0.14), whereas HPC1 LOD scores were all
negative. In HOMOG3R analyses, significant evidence of
heterogeneity was observed. Subgroup analyses performed to explore the
nature of this heterogeneity indicated that families with no
male-to-male (NMM) transmission and a late age of diagnosis (>65
years) accounted for most of the HPCX -linked cases. The
maximum HPCX LOD score in this subgroup was 3.12
(θ = 0.001). Nonparametric sibling pair analyses gave a peak LOD
score of 3.04 ( P < 0.000093) for the NMM
transmission subgroup. No subgroup showed any positivity for
HPC1 . This study suggests that the
HPCX -linked prostate cancer families represent a
distinct subgroup characterized by NMM transmission of disease and late
age of diagnosis.
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