AustralieFrV1, Main, Exploration, bibRecord, 008591

Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

Identifieur interne : 008591 ( Main/Exploration ); précédent : 008590; suivant : 008592

Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

Auteurs : Liesel M. Fitzgerald [Australie] ; Briony Patterson [Australie] ; Russell Thomson [Australie] ; Andrea Polanowski [Australie] ; Stephen Quinn [Australie] ; Jesper Brohede [Suède] ; Timothy Thornton [États-Unis] ; David Challis [Australie] ; David A. Mackey [Australie] ; Terence Dwyer [Australie] ; Simon Foote [Australie] ; Garry N. Hannan [Australie] ; James Stankovich [Australie] ; James D. Mckay [Australie, France] ; Joanne L. Dickinson [Australie]

Source :

European Journal of Human Genetics [ 1018-4813 ] ; 2008.

RBID : PMC:2986161

Abstract

Genetic heterogeneity is a difficulty frequently encountered in the search for genes conferring susceptibility to prostate cancer. To circumvent this issue, we selected a large prostate cancer pedigree for genome-wide linkage analysis from a population that is genetically homogeneous. Selected cases and first-degree relatives were genotyped with Affymetrix 10K SNP arrays, identifying a 14 Mb haplotype on chromosome 5 (5p13–q12) inherited identical-by-descent (IBD) by multiple cases. Microsatellite genotyping of additional deceased case samples confirmed that a total of eight cases inherited the common haplotype (P=0.0017). Re-sequencing of eight prioritised candidate genes in the region in six selected individuals identified 15 SNPs segregating with the IBD haplotype, located within the ITGA2 gene. Three of these polymorphisms were selected for genotyping in an independent Tasmanian data set comprising 127 cases with familial prostate cancer, 412 sporadic cases and 319 unaffected controls. Two were associated with prostate cancer risk: rs3212649 (OR=1.67 (1.07–2.6), P=0.0009) and rs1126643 (OR=1.52 (1.01–2.28), P=0.0088). Significant association was observed in both familial and sporadic prostate cancer. Although the functional SNP remains to be identified, considerable circumstantial evidence, provided by in vivo and in vitro studies, supports a role for ITGA2 in tumour development.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2986161

DOI: 10.1038/ejhg.2008.171
PubMed: 18830231
PubMed Central: 2986161

Affiliations:

Australie, France, Suède, États-Unis

Le document en format XML

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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<country xml:lang="fr">Australie</country>
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, Hobart,<country>Australia</country>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Hannan, Garry N" sort="Hannan, Garry N" uniqKey="Hannan G" first="Garry N" last="Hannan">Garry N. Hannan</name>
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, Melbourne,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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, Lyon,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Dickinson, Joanne L" sort="Dickinson, Joanne L" uniqKey="Dickinson J" first="Joanne L" last="Dickinson">Joanne L. Dickinson</name>
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, Hobart,<country>Australia</country>
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<series><title level="j">European Journal of Human Genetics</title>
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<front><div type="abstract" xml:lang="en"><p>Genetic heterogeneity is a difficulty frequently encountered in the search for genes conferring susceptibility to prostate cancer. To circumvent this issue, we selected a large prostate cancer pedigree for genome-wide linkage analysis from a population that is genetically homogeneous. Selected cases and first-degree relatives were genotyped with Affymetrix 10K SNP arrays, identifying a 14 Mb haplotype on chromosome 5 (5p13–q12) inherited identical-by-descent (IBD) by multiple cases. Microsatellite genotyping of additional deceased case samples confirmed that a total of eight cases inherited the common haplotype (<italic>P</italic>
=0.0017). Re-sequencing of eight prioritised candidate genes in the region in six selected individuals identified 15 SNPs segregating with the IBD haplotype, located within the <italic>ITGA2</italic>
 gene. Three of these polymorphisms were selected for genotyping in an independent Tasmanian data set comprising 127 cases with familial prostate cancer, 412 sporadic cases and 319 unaffected controls. Two were associated with prostate cancer risk: rs3212649 (OR=1.67 (1.07–2.6), <italic>P</italic>
=0.0009) and rs1126643 (OR=1.52 (1.01–2.28), <italic>P</italic>
=0.0088). Significant association was observed in both familial and sporadic prostate cancer. Although the functional SNP remains to be identified, considerable circumstantial evidence, provided by <italic>in vivo</italic>
 and <italic>in vitro</italic>
 studies, supports a role for <italic>ITGA2</italic>
 in tumour development.</p>
</div>
</front>
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{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:2986161
   |texte=   Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease
}}

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Serveur d'exploration sur les relations entre la France et l'Australie

Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

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Abstract

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	Serveur d'exploration sur les relations entre la France et l'Australie
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