ParkinsonCanadaV1, Pmc, Corpus, bibRecord, 000794

Genetic Variants Associated with Breast Cancer Risk for Ashkenazi Jewish Women with Strong Family Histories but No Identifiable BRCA1/2 Mutation

Identifieur interne : 000794 ( Pmc/Corpus ); précédent : 000793; suivant : 000795

Genetic Variants Associated with Breast Cancer Risk for Ashkenazi Jewish Women with Strong Family Histories but No Identifiable BRCA1/2 Mutation

Auteurs : Erica S. Rinella ; Yongzhao Shao ; Lauren Yackowski ; Sreemanta Pramanik ; Ruth Oratz ; Freya Schnabel ; Saurav Guha ; Charles Leduc ; Chris Campbell ; Susan D. Klugman ; Mary Beth Terry ; Ruby T. Senie ; Irene L. Andrulis ; Mary Daly ; Esther M. John ; Daniel Roses ; Wendy K. Chung ; Harry Ostrer

Source :

Human genetics [ 0340-6717 ] ; 2013.

RBID : PMC:4072456

Abstract

Background

The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations.

Methods

This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts were comprised of 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation.

Results

A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. Additionally, 6 previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, 3 novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and 3 previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74.

Conclusion

Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072456

DOI: 10.1007/s00439-013-1269-4
PubMed: 23354978
PubMed Central: 4072456

Links to Exploration step

PMC:4072456

Le document en format XML

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 Mutation</title>
<author><name sortKey="Rinella, Erica S" sort="Rinella, Erica S" uniqKey="Rinella E" first="Erica S." last="Rinella">Erica S. Rinella</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shao, Yongzhao" sort="Shao, Yongzhao" uniqKey="Shao Y" first="Yongzhao" last="Shao">Yongzhao Shao</name>
<affiliation><nlm:aff id="A2">Division of Biostatistics, New York University School of Medicine, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yackowski, Lauren" sort="Yackowski, Lauren" uniqKey="Yackowski L" first="Lauren" last="Yackowski">Lauren Yackowski</name>
<affiliation><nlm:aff id="A3">Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pramanik, Sreemanta" sort="Pramanik, Sreemanta" uniqKey="Pramanik S" first="Sreemanta" last="Pramanik">Sreemanta Pramanik</name>
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</affiliation>
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<author><name sortKey="Oratz, Ruth" sort="Oratz, Ruth" uniqKey="Oratz R" first="Ruth" last="Oratz">Ruth Oratz</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schnabel, Freya" sort="Schnabel, Freya" uniqKey="Schnabel F" first="Freya" last="Schnabel">Freya Schnabel</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guha, Saurav" sort="Guha, Saurav" uniqKey="Guha S" first="Saurav" last="Guha">Saurav Guha</name>
<affiliation><nlm:aff id="A5">Department of Pediatrics, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Leduc, Charles" sort="Leduc, Charles" uniqKey="Leduc C" first="Charles" last="Leduc">Charles Leduc</name>
<affiliation><nlm:aff id="A5">Department of Pediatrics, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Campbell, Chris" sort="Campbell, Chris" uniqKey="Campbell C" first="Chris" last="Campbell">Chris Campbell</name>
<affiliation><nlm:aff id="A3">Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Klugman, Susan D" sort="Klugman, Susan D" uniqKey="Klugman S" first="Susan D." last="Klugman">Susan D. Klugman</name>
<affiliation><nlm:aff id="A6">Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Terry, Mary Beth" sort="Terry, Mary Beth" uniqKey="Terry M" first="Mary Beth" last="Terry">Mary Beth Terry</name>
<affiliation><nlm:aff id="A7">Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Senie, Ruby T" sort="Senie, Ruby T" uniqKey="Senie R" first="Ruby T." last="Senie">Ruby T. Senie</name>
<affiliation><nlm:aff id="A7">Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L." last="Andrulis">Irene L. Andrulis</name>
<affiliation><nlm:aff id="A8">Department of Molecular Genetics, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Daly, Mary" sort="Daly, Mary" uniqKey="Daly M" first="Mary" last="Daly">Mary Daly</name>
<affiliation><nlm:aff id="A9">Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="John, Esther M" sort="John, Esther M" uniqKey="John E" first="Esther M." last="John">Esther M. John</name>
<affiliation><nlm:aff id="A10">Cancer Prevention Institute of California, Fremont, CA and Stanford University School of Medicine & Stanford Cancer Institute, Stanford, CA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Roses, Daniel" sort="Roses, Daniel" uniqKey="Roses D" first="Daniel" last="Roses">Daniel Roses</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chung, Wendy K" sort="Chung, Wendy K" uniqKey="Chung W" first="Wendy K." last="Chung">Wendy K. Chung</name>
<affiliation><nlm:aff id="A5">Department of Pediatrics, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ostrer, Harry" sort="Ostrer, Harry" uniqKey="Ostrer H" first="Harry" last="Ostrer">Harry Ostrer</name>
<affiliation><nlm:aff id="A3">Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA</nlm:aff>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genetic Variants Associated with Breast Cancer Risk for Ashkenazi Jewish Women with Strong Family Histories but No Identifiable <italic>BRCA1/2</italic>
 Mutation</title>
<author><name sortKey="Rinella, Erica S" sort="Rinella, Erica S" uniqKey="Rinella E" first="Erica S." last="Rinella">Erica S. Rinella</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shao, Yongzhao" sort="Shao, Yongzhao" uniqKey="Shao Y" first="Yongzhao" last="Shao">Yongzhao Shao</name>
<affiliation><nlm:aff id="A2">Division of Biostatistics, New York University School of Medicine, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yackowski, Lauren" sort="Yackowski, Lauren" uniqKey="Yackowski L" first="Lauren" last="Yackowski">Lauren Yackowski</name>
<affiliation><nlm:aff id="A3">Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pramanik, Sreemanta" sort="Pramanik, Sreemanta" uniqKey="Pramanik S" first="Sreemanta" last="Pramanik">Sreemanta Pramanik</name>
<affiliation><nlm:aff id="A4">Kolkata Zonal Laboratory, National Environmental Engineering Research Institute, Kolkata, India</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oratz, Ruth" sort="Oratz, Ruth" uniqKey="Oratz R" first="Ruth" last="Oratz">Ruth Oratz</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schnabel, Freya" sort="Schnabel, Freya" uniqKey="Schnabel F" first="Freya" last="Schnabel">Freya Schnabel</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guha, Saurav" sort="Guha, Saurav" uniqKey="Guha S" first="Saurav" last="Guha">Saurav Guha</name>
<affiliation><nlm:aff id="A5">Department of Pediatrics, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Leduc, Charles" sort="Leduc, Charles" uniqKey="Leduc C" first="Charles" last="Leduc">Charles Leduc</name>
<affiliation><nlm:aff id="A5">Department of Pediatrics, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Campbell, Chris" sort="Campbell, Chris" uniqKey="Campbell C" first="Chris" last="Campbell">Chris Campbell</name>
<affiliation><nlm:aff id="A3">Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Klugman, Susan D" sort="Klugman, Susan D" uniqKey="Klugman S" first="Susan D." last="Klugman">Susan D. Klugman</name>
<affiliation><nlm:aff id="A6">Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Terry, Mary Beth" sort="Terry, Mary Beth" uniqKey="Terry M" first="Mary Beth" last="Terry">Mary Beth Terry</name>
<affiliation><nlm:aff id="A7">Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Senie, Ruby T" sort="Senie, Ruby T" uniqKey="Senie R" first="Ruby T." last="Senie">Ruby T. Senie</name>
<affiliation><nlm:aff id="A7">Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L." last="Andrulis">Irene L. Andrulis</name>
<affiliation><nlm:aff id="A8">Department of Molecular Genetics, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Daly, Mary" sort="Daly, Mary" uniqKey="Daly M" first="Mary" last="Daly">Mary Daly</name>
<affiliation><nlm:aff id="A9">Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="John, Esther M" sort="John, Esther M" uniqKey="John E" first="Esther M." last="John">Esther M. John</name>
<affiliation><nlm:aff id="A10">Cancer Prevention Institute of California, Fremont, CA and Stanford University School of Medicine & Stanford Cancer Institute, Stanford, CA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Roses, Daniel" sort="Roses, Daniel" uniqKey="Roses D" first="Daniel" last="Roses">Daniel Roses</name>
<affiliation><nlm:aff id="A1">Department of Surgery, New York University Langone Medical Center, New York, NY USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chung, Wendy K" sort="Chung, Wendy K" uniqKey="Chung W" first="Wendy K." last="Chung">Wendy K. Chung</name>
<affiliation><nlm:aff id="A5">Department of Pediatrics, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ostrer, Harry" sort="Ostrer, Harry" uniqKey="Ostrer H" first="Harry" last="Ostrer">Harry Ostrer</name>
<affiliation><nlm:aff id="A3">Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Human genetics</title>
<idno type="ISSN">0340-6717</idno>
<idno type="eISSN">1432-1203</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome wide association studies (GWAS). This is especially true for women at high risk because of family history, but without <italic>BRCA1/2</italic>
 mutations.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts were comprised of 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an <italic>FGFR2</italic>
 haplotype. Additionally, 6 previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, 3 novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the <italic>FGFR2</italic>
 haplotype, and 3 previously published SNPs [rs13387042(2q35), rs2046210(<italic>ESR1</italic>
), and rs3112612(<italic>TOX3</italic>
)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder <italic>BRCA1/2</italic>
 mutations.</p>
</sec>
</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>
  <pmc-dir>properties manuscript</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-journal-id">7613873</journal-id>
<journal-id journal-id-type="pubmed-jr-id">4137</journal-id>
<journal-id journal-id-type="nlm-ta">Hum Genet</journal-id>
<journal-id journal-id-type="iso-abbrev">Hum. Genet.</journal-id>
<journal-title-group><journal-title>Human genetics</journal-title>
</journal-title-group>
<issn pub-type="ppub">0340-6717</issn>
<issn pub-type="epub">1432-1203</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23354978</article-id>
<article-id pub-id-type="pmc">4072456</article-id>
<article-id pub-id-type="doi">10.1007/s00439-013-1269-4</article-id>
<article-id pub-id-type="manuscript">NIHMS439382</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Genetic Variants Associated with Breast Cancer Risk for Ashkenazi Jewish Women with Strong Family Histories but No Identifiable <italic>BRCA1/2</italic>
 Mutation</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Rinella</surname>
<given-names>Erica S.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shao</surname>
<given-names>Yongzhao</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yackowski</surname>
<given-names>Lauren</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pramanik</surname>
<given-names>Sreemanta</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oratz</surname>
<given-names>Ruth</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schnabel</surname>
<given-names>Freya</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Guha</surname>
<given-names>Saurav</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>LeDuc</surname>
<given-names>Charles</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Campbell</surname>
<given-names>Chris</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Klugman</surname>
<given-names>Susan D.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Terry</surname>
<given-names>Mary Beth</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Senie</surname>
<given-names>Ruby T.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Andrulis</surname>
<given-names>Irene L.</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Daly</surname>
<given-names>Mary</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>John</surname>
<given-names>Esther M.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Roses</surname>
<given-names>Daniel</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chung</surname>
<given-names>Wendy K.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ostrer</surname>
<given-names>Harry</given-names>
</name>
<xref rid="FN1" ref-type="author-notes">*</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Surgery, New York University Langone Medical Center, New York, NY USA</aff>
<aff id="A2"><label>2</label>
Division of Biostatistics, New York University School of Medicine, New York, NY, USA</aff>
<aff id="A3"><label>3</label>
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA</aff>
<aff id="A4"><label>4</label>
Kolkata Zonal Laboratory, National Environmental Engineering Research Institute, Kolkata, India</aff>
<aff id="A5"><label>5</label>
Department of Pediatrics, Columbia University Medical Center, New York, NY, USA</aff>
<aff id="A6"><label>6</label>
Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY USA</aff>
<aff id="A7"><label>7</label>
Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY, USA</aff>
<aff id="A8"><label>8</label>
Department of Molecular Genetics, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada</aff>
<aff id="A9"><label>9</label>
Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA</aff>
<aff id="A10"><label>10</label>
Cancer Prevention Institute of California, Fremont, CA and Stanford University School of Medicine & Stanford Cancer Institute, Stanford, CA, USA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Correspondence: Harry Ostrer, Department of Pathology, Ullman 715, 1300 Morris Park Rd, Bronx, NY 10461, (718)430-8605, <email>harry.ostrer@einstein.yu.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>21</day>
<month>5</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>25</day>
<month>1</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub"><month>5</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>26</day>
<month>6</month>
<year>2014</year>
</pub-date>
<volume>132</volume>
<issue>5</issue>
<fpage>523</fpage>
<lpage>536</lpage>
<pmc-comment>elocation-id from pubmed: 10.1007/s00439-013-1269-4</pmc-comment>
      <abstract><sec id="S1"><title>Background</title>
<p id="P1">The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome wide association studies (GWAS). This is especially true for women at high risk because of family history, but without <italic>BRCA1/2</italic>
 mutations.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts were comprised of 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an <italic>FGFR2</italic>
 haplotype. Additionally, 6 previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, 3 novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the <italic>FGFR2</italic>
 haplotype, and 3 previously published SNPs [rs13387042(2q35), rs2046210(<italic>ESR1</italic>
), and rs3112612(<italic>TOX3</italic>
)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder <italic>BRCA1/2</italic>
 mutations.</p>
</sec>
</abstract>
<kwd-group><kwd>Ashkenazi Jewish</kwd>
<kwd>breast cancer</kwd>
<kwd>genome-wide association study</kwd>
<kwd>SNP</kwd>
<kwd>risk model</kwd>
<kwd>AUC</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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	La maladie de Parkinson au Canada (serveur d'exploration)
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La maladie de Parkinson au Canada (serveur d'exploration)

Genetic Variants Associated with Breast Cancer Risk for Ashkenazi Jewish Women with Strong Family Histories but No Identifiable BRCA1/2 Mutation

Genetic Variants Associated with Breast Cancer Risk for Ashkenazi Jewish Women with Strong Family Histories but No Identifiable BRCA1/2 Mutation

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