TY - JOUR
T1 - A major locus for hereditary prostate cancer in Finland
T2 - Localization by linkage disequilibrium of a haplotype in the HPCX region
AU - Baffoe-Bonnie, A.B.
AU - Smith, J.R.
AU - Stephan, D.A.
AU - Schleutker, J.
AU - Carpten, J.D.
AU - Kainu, T.
AU - Gillanders, E.M.
AU - Matikainen, M.
AU - Teslovich, T.M.
AU - Tammela, T.
AU - Sood, R.
AU - Balshem, A.M.
AU - Scarborough, S.D.
AU - Xu, J.
AU - Isaacs, W.B.
AU - Trent, J.M.
AU - Kallioniemi, Olli
AU - Bailey-Wilson, J.E.
PY - 2005
Y1 - 2005
N2 - Background: Prostate cancer (PRCA)
is the most common cancer in males in the western world. In Finland PRCA
has an age-adjusted incidence of 81.5 per 100,000. We previously
reported that in Finland, the late-onset cases in families with
“no-male-to-male” (NMM) transmission of PRCA accounted for most of the
linkage to the HPCX region
(Xq27-28). The aim of the present study was to test for linkage
disequilibrium (LD) and haplotype-sharing around marker DXS1205 between
cases from hereditary prostate cancer (HPC) families and population
controls. The initial allelic association was performed between 108 PRCA
cases and 257 population controls genotyped for 23 markers in the
Xq26-28 region. This resulted in a highly significant nominal one-sided
Fisher’s exact P-value of 0.0003
for allele ″180″ of marker DXS1205. Subsequently, a similar level of
significance was observed for the same allele for marker DXS1205 (P=0.0002)
when comparing 60 NMM cases and 257 controls. These results were still
significant after Bonferroni correction for multiple testing. Fine
mapping efforts included the genotyping of four additional markers
D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide
polymorphisms (SNPs) to augment the original markers around DXS1205. Results:
Our major finding is that markers extending from ″D3S2390″ to
″bG82i1.0″ flank the critical locus, about 150 kb. Levin and Bertell’s
LD measure (δ), a guide to localization of a possible variant, was 0.42
and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. Conclusions:
In this study, the most significant haplotype comprised the three
tightly linked, contiguous markers:
″cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel″ [″197-2-234″] among several
possible haplotypes (nominal Fisher’s one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX
gene(s) is being facilitated by this exploration of the Xq26-28 region.
This study represents the first report identifying a haplotype in the
Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.
AB - Background: Prostate cancer (PRCA)
is the most common cancer in males in the western world. In Finland PRCA
has an age-adjusted incidence of 81.5 per 100,000. We previously
reported that in Finland, the late-onset cases in families with
“no-male-to-male” (NMM) transmission of PRCA accounted for most of the
linkage to the HPCX region
(Xq27-28). The aim of the present study was to test for linkage
disequilibrium (LD) and haplotype-sharing around marker DXS1205 between
cases from hereditary prostate cancer (HPC) families and population
controls. The initial allelic association was performed between 108 PRCA
cases and 257 population controls genotyped for 23 markers in the
Xq26-28 region. This resulted in a highly significant nominal one-sided
Fisher’s exact P-value of 0.0003
for allele ″180″ of marker DXS1205. Subsequently, a similar level of
significance was observed for the same allele for marker DXS1205 (P=0.0002)
when comparing 60 NMM cases and 257 controls. These results were still
significant after Bonferroni correction for multiple testing. Fine
mapping efforts included the genotyping of four additional markers
D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide
polymorphisms (SNPs) to augment the original markers around DXS1205. Results:
Our major finding is that markers extending from ″D3S2390″ to
″bG82i1.0″ flank the critical locus, about 150 kb. Levin and Bertell’s
LD measure (δ), a guide to localization of a possible variant, was 0.42
and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. Conclusions:
In this study, the most significant haplotype comprised the three
tightly linked, contiguous markers:
″cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel″ [″197-2-234″] among several
possible haplotypes (nominal Fisher’s one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX
gene(s) is being facilitated by this exploration of the Xq26-28 region.
This study represents the first report identifying a haplotype in the
Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.
U2 - 10.1007/s00439-005-1306-z
DO - 10.1007/s00439-005-1306-z
M3 - Article
SN - 0340-6717
VL - 117
SP - 307
EP - 316
JO - Human Genetics
JF - Human Genetics
IS - 4
ER -
