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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease</title><author><name sortKey="Fitzgerald, Liesel M" sort="Fitzgerald, Liesel M" uniqKey="Fitzgerald L" first="Liesel M" last="Fitzgerald">Liesel M. Fitzgerald</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Patterson, Briony" sort="Patterson, Briony" uniqKey="Patterson B" first="Briony" last="Patterson">Briony Patterson</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Thomson, Russell" sort="Thomson, Russell" uniqKey="Thomson R" first="Russell" last="Thomson">Russell Thomson</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Polanowski, Andrea" sort="Polanowski, Andrea" uniqKey="Polanowski A" first="Andrea" last="Polanowski">Andrea Polanowski</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Quinn, Stephen" sort="Quinn, Stephen" uniqKey="Quinn S" first="Stephen" last="Quinn">Stephen Quinn</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Brohede, Jesper" sort="Brohede, Jesper" uniqKey="Brohede J" first="Jesper" last="Brohede">Jesper Brohede</name><affiliation><nlm:aff id="aff2"><institution>Karolinska Institutet, KI-Alzheimer Disease Research Centre</institution>, Stockholm,<country>Sweden</country></nlm:aff></affiliation></author><author><name sortKey="Thornton, Timothy" sort="Thornton, Timothy" uniqKey="Thornton T" first="Timothy" last="Thornton">Timothy Thornton</name><affiliation><nlm:aff id="aff3"><institution>Department of Statistics, University of California</institution>,<country>Berkeley, CA, USA</country></nlm:aff></affiliation></author><author><name sortKey="Challis, David" sort="Challis, David" uniqKey="Challis D" first="David" last="Challis">David Challis</name><affiliation><nlm:aff id="aff4"><institution>Histopathology Department, Royal Hobart Hospital</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A" last="Mackey">David A. Mackey</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><institution>Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital</institution>, East Melbourne,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution>Department of Ophthalmology, Royal Children's Hospital</institution>, Melbourne,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Dwyer, Terence" sort="Dwyer, Terence" uniqKey="Dwyer T" first="Terence" last="Dwyer">Terence Dwyer</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff7"><institution>Murdoch Children's Research Institute</institution>, Melbourne,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Foote, Simon" sort="Foote, Simon" uniqKey="Foote S" first="Simon" last="Foote">Simon Foote</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Hannan, Garry N" sort="Hannan, Garry N" uniqKey="Hannan G" first="Garry N" last="Hannan">Garry N. Hannan</name><affiliation><nlm:aff id="aff8"><institution>CSIRO Preventative Health National Research Flagship</institution>, North Ryde, New South Wales,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff9"><institution>CSIRO Molecular and Health Technologies</institution>, North Ryde, New South Wales,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Stankovich, James" sort="Stankovich, James" uniqKey="Stankovich J" first="James" last="Stankovich">James Stankovich</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"><institution>Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research</institution>, Melbourne,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mckay, James D" sort="Mckay, James D" uniqKey="Mckay J" first="James D" last="Mckay">James D. Mckay</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><institution>International Agency for Research on Cancer</institution>, Lyon,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Dickinson, Joanne L" sort="Dickinson, Joanne L" uniqKey="Dickinson J" first="Joanne L" last="Dickinson">Joanne L. Dickinson</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18830231</idno><idno type="pmc">2986161</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2986161</idno><idno type="RBID">PMC:2986161</idno><idno type="doi">10.1038/ejhg.2008.171</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000050</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000050</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease</title><author><name sortKey="Fitzgerald, Liesel M" sort="Fitzgerald, Liesel M" uniqKey="Fitzgerald L" first="Liesel M" last="Fitzgerald">Liesel M. Fitzgerald</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Patterson, Briony" sort="Patterson, Briony" uniqKey="Patterson B" first="Briony" last="Patterson">Briony Patterson</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Thomson, Russell" sort="Thomson, Russell" uniqKey="Thomson R" first="Russell" last="Thomson">Russell Thomson</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Polanowski, Andrea" sort="Polanowski, Andrea" uniqKey="Polanowski A" first="Andrea" last="Polanowski">Andrea Polanowski</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Quinn, Stephen" sort="Quinn, Stephen" uniqKey="Quinn S" first="Stephen" last="Quinn">Stephen Quinn</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Brohede, Jesper" sort="Brohede, Jesper" uniqKey="Brohede J" first="Jesper" last="Brohede">Jesper Brohede</name><affiliation><nlm:aff id="aff2"><institution>Karolinska Institutet, KI-Alzheimer Disease Research Centre</institution>, Stockholm,<country>Sweden</country></nlm:aff></affiliation></author><author><name sortKey="Thornton, Timothy" sort="Thornton, Timothy" uniqKey="Thornton T" first="Timothy" last="Thornton">Timothy Thornton</name><affiliation><nlm:aff id="aff3"><institution>Department of Statistics, University of California</institution>,<country>Berkeley, CA, USA</country></nlm:aff></affiliation></author><author><name sortKey="Challis, David" sort="Challis, David" uniqKey="Challis D" first="David" last="Challis">David Challis</name><affiliation><nlm:aff id="aff4"><institution>Histopathology Department, Royal Hobart Hospital</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A" last="Mackey">David A. Mackey</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><institution>Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital</institution>, East Melbourne,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution>Department of Ophthalmology, Royal Children's Hospital</institution>, Melbourne,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Dwyer, Terence" sort="Dwyer, Terence" uniqKey="Dwyer T" first="Terence" last="Dwyer">Terence Dwyer</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff7"><institution>Murdoch Children's Research Institute</institution>, Melbourne,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Foote, Simon" sort="Foote, Simon" uniqKey="Foote S" first="Simon" last="Foote">Simon Foote</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Hannan, Garry N" sort="Hannan, Garry N" uniqKey="Hannan G" first="Garry N" last="Hannan">Garry N. Hannan</name><affiliation><nlm:aff id="aff8"><institution>CSIRO Preventative Health National Research Flagship</institution>, North Ryde, New South Wales,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff9"><institution>CSIRO Molecular and Health Technologies</institution>, North Ryde, New South Wales,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Stankovich, James" sort="Stankovich, James" uniqKey="Stankovich J" first="James" last="Stankovich">James Stankovich</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"><institution>Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research</institution>, Melbourne,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mckay, James D" sort="Mckay, James D" uniqKey="Mckay J" first="James D" last="Mckay">James D. Mckay</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><institution>International Agency for Research on Cancer</institution>, Lyon,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Dickinson, Joanne L" sort="Dickinson, Joanne L" uniqKey="Dickinson J" first="Joanne L" last="Dickinson">Joanne L. Dickinson</name><affiliation><nlm:aff id="aff1"><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></nlm:aff></affiliation></author></analytic><series><title level="j">European Journal of Human Genetics</title><idno type="ISSN">1018-4813</idno><idno type="eISSN">1476-5438</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Eur J Hum Genet</journal-id><journal-title-group><journal-title>European Journal of Human Genetics</journal-title></journal-title-group><issn pub-type="ppub">1018-4813</issn><issn pub-type="epub">1476-5438</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18830231</article-id><article-id pub-id-type="pmc">2986161</article-id><article-id pub-id-type="pii">ejhg2008171</article-id><article-id pub-id-type="doi">10.1038/ejhg.2008.171</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease</article-title><alt-title alt-title-type="running">Prostate cancer susceptibility gene on chromosome 5</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>FitzGerald</surname><given-names>Liesel M</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Patterson</surname><given-names>Briony</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Thomson</surname><given-names>Russell</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Polanowski</surname><given-names>Andrea</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Quinn</surname><given-names>Stephen</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Brohede</surname><given-names>Jesper</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Thornton</surname><given-names>Timothy</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Challis</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Mackey</surname><given-names>David A</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Dwyer</surname><given-names>Terence</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Foote</surname><given-names>Simon</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hannan</surname><given-names>Garry N</given-names></name><xref ref-type="aff" rid="aff8">8</xref><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Stankovich</surname><given-names>James</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>McKay</surname><given-names>James D</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Dickinson</surname><given-names>Joanne L</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><aff id="aff1"><label>1</label><institution>Genetics Unit, Menzies Research Institute, University of Tasmania</institution>, Hobart,<country>Australia</country></aff><aff id="aff2"><label>2</label><institution>Karolinska Institutet, KI-Alzheimer Disease Research Centre</institution>, Stockholm,<country>Sweden</country></aff><aff id="aff3"><label>3</label><institution>Department of Statistics, University of California</institution>,<country>Berkeley, CA, USA</country></aff><aff id="aff4"><label>4</label><institution>Histopathology Department, Royal Hobart Hospital</institution>, Hobart,<country>Australia</country></aff><aff id="aff5"><label>5</label><institution>Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital</institution>, East Melbourne,<country>Australia</country></aff><aff id="aff6"><label>6</label><institution>Department of Ophthalmology, Royal Children's Hospital</institution>, Melbourne,<country>Australia</country></aff><aff id="aff7"><label>7</label><institution>Murdoch Children's Research Institute</institution>, Melbourne,<country>Australia</country></aff><aff id="aff8"><label>8</label><institution>CSIRO Preventative Health National Research Flagship</institution>, North Ryde, New South Wales,<country>Australia</country></aff><aff id="aff9"><label>9</label><institution>CSIRO Molecular and Health Technologies</institution>, North Ryde, New South Wales,<country>Australia</country></aff><aff id="aff10"><label>10</label><institution>Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research</institution>, Melbourne,<country>Australia</country></aff><aff id="aff11"><label>11</label><institution>International Agency for Research on Cancer</institution>, Lyon,<country>France</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label><institution>Menzies Research Institute</institution>, Private Bag 23, Hobart, Tasmania 7001, <country>Australia</country>. Tel: +61 3 62267622; Fax: +61 3 62267704; E-mail: <email>jo.dickinson@utas.edu.au</email></corresp></author-notes><pub-date pub-type="ppub"><month>03</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>01</day><month>10</month><year>2008</year></pub-date><volume>17</volume><issue>3</issue><fpage>368</fpage><lpage>377</lpage><history><date date-type="received"><day>06</day><month>06</month><year>2008</year></date><date date-type="rev-recd"><day>25</day><month>07</month><year>2008</year></date><date date-type="accepted"><day>29</day><month>08</month><year>2008</year></date></history><permissions><copyright-statement>Copyright © 2009 Nature Publishing Group</copyright-statement><copyright-year>2009</copyright-year><copyright-holder>Nature Publishing Group</copyright-holder></permissions><abstract><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></abstract><kwd-group><kwd>genetic</kwd><kwd>susceptibility</kwd><kwd>prostate</kwd><kwd>cancer</kwd><kwd>risk</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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