LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease
Identifieur interne : 000227 ( Main/Corpus ); précédent : 000226; suivant : 000228LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease
Auteurs : Rachel Saunders-Pullman ; Matthew J. Barrett ; Kaili M. Stanley ; Marta San Luciano ; Vicki Shanker ; Lawrence Severt ; Ann Hunt ; Deborah Raymond ; Laurie J. Ozelius ; Susan B. BressmanSource :
- Movement Disorders [ 0885-3185 ] ; 2010-11-15.
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Abstract
Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase. Small molecule kinase inhibitors have been developed for the treatment of certain cancers, and some antioncogenic agents such as sunitinib, may nonspecifically inhibit LRRK2. Few studies, however, have assessed cancer risk in LRRK2 mutation carriers. To explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients participating in genetic research. Charts were reviewed for 163 unrelated AJ PD patients, 31 of whom harbored the G2019S mutation. History of cancer was queried at baseline intake using a form reviewing medical conditions, and charts were reviewed for all follow‐up visits. 9/31 LRRK2 G2019S mutation carriers had nonskin cancers, whereas 15/132 without mutations had nonskin cancers, representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3–6.6). Age at first nonskin cancer was younger in the LRRK2 carriers (56.0 years) than the noncarriers (62.0 years), but was not significant. 67% of the LRRK2 carriers had their cancer before the onset of PD, whereas only 40% of noncarriers developed their first nonskin cancer before onset of PD. While further evaluation is warranted, our findings indicate an increased risk of nonskin cancers in LRRK2 G2019S mutation carriers, which may be related to toxic gain of function of mutated LRRK2. © 2010 Movement Disorder Society
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DOI: 10.1002/mds.23314
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Ozelius</name><affiliation><mods:affiliation>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name><affiliation><mods:affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. 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Small molecule kinase inhibitors have been developed for the treatment of certain cancers, and some antioncogenic agents such as sunitinib, may nonspecifically inhibit LRRK2. Few studies, however, have assessed cancer risk in LRRK2 mutation carriers. To explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients participating in genetic research. Charts were reviewed for 163 unrelated AJ PD patients, 31 of whom harbored the G2019S mutation. History of cancer was queried at baseline intake using a form reviewing medical conditions, and charts were reviewed for all follow‐up visits. 9/31 LRRK2 G2019S mutation carriers had nonskin cancers, whereas 15/132 without mutations had nonskin cancers, representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3–6.6). Age at first nonskin cancer was younger in the LRRK2 carriers (56.0 years) than the noncarriers (62.0 years), but was not significant. 67% of the LRRK2 carriers had their cancer before the onset of PD, whereas only 40% of noncarriers developed their first nonskin cancer before onset of PD. While further evaluation is warranted, our findings indicate an increased risk of nonskin cancers in LRRK2 G2019S mutation carriers, which may be related to toxic gain of function of mutated LRRK2. © 2010 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Rachel Saunders‐Pullman MD, MPH</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string><json:string>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</json:string></affiliations></json:item><json:item><name>Matthew J. Barrett MD</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Kaili M. Stanley BS</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Marta San Luciano MD</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Vicki Shanker MD</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string><json:string>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</json:string></affiliations></json:item><json:item><name>Lawrence Severt MD, PhD</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Ann Hunt DO</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Deborah Raymond MS</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Laurie J. Ozelius PhD</name><affiliations><json:string>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA</json:string><json:string>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Susan B. Bressman MD</name><affiliations><json:string>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</json:string><json:string>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>genetics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LRRK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>cancer</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>search terms</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LRRK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>cancer</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>renal cancer</value></json:item></subject><articleId><json:string>MDS23314</json:string></articleId><language><json:string>eng</json:string></language><abstract>Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase. Small molecule kinase inhibitors have been developed for the treatment of certain cancers, and some antioncogenic agents such as sunitinib, may nonspecifically inhibit LRRK2. Few studies, however, have assessed cancer risk in LRRK2 mutation carriers. To explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients participating in genetic research. Charts were reviewed for 163 unrelated AJ PD patients, 31 of whom harbored the G2019S mutation. History of cancer was queried at baseline intake using a form reviewing medical conditions, and charts were reviewed for all follow‐up visits. 9/31 LRRK2 G2019S mutation carriers had nonskin cancers, whereas 15/132 without mutations had nonskin cancers, representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3–6.6). Age at first nonskin cancer was younger in the LRRK2 carriers (56.0 years) than the noncarriers (62.0 years), but was not significant. 67% of the LRRK2 carriers had their cancer before the onset of PD, whereas only 40% of noncarriers developed their first nonskin cancer before onset of PD. While further evaluation is warranted, our findings indicate an increased risk of nonskin cancers in LRRK2 G2019S mutation carriers, which may be related to toxic gain of function of mutated LRRK2. © 2010 Movement Disorder Society</abstract><qualityIndicators><score>6.051</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>9</keywordCount><abstractCharCount>1458</abstractCharCount><pdfWordCount>3339</pdfWordCount><pdfCharCount>22140</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>226</abstractWordCount></qualityIndicators><title>LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease</title><genre><json:string>article</json:string></genre><host><volume>25</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>6</total><last>2541</last><first>2536</first></pages><issn><json:string>0885-3185</json:string></issn><issue>15</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8257</json:string></eissn><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/mds.23314</json:string></doi><id>4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2010</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: Nothing to report.</note><note>National Institute of Neurological Disorders and Stroke - No. K23NS047256;</note><note>Michael J. Fox Foundation</note><note>Thomas Hartman Foundation for Parkinson's Research</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease</title><author><persName><forename type="first">Rachel</forename><surname>Saunders‐Pullman</surname></persName><roleName type="degree">MD, MPH</roleName><note type="correspondence"><p>Correspondence: The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003.Department of Neurology, Beth Israel Medical Center, New York, NY, USA</p></note><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><affiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</affiliation></author><author><persName><forename type="first">Matthew J.</forename><surname>Barrett</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation></author><author><persName><forename type="first">Kaili M.</forename><surname>Stanley</surname></persName><roleName type="degree">BS</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation></author><author><persName><forename type="first">Marta San</forename><surname>Luciano</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation></author><author><persName><forename type="first">Vicki</forename><surname>Shanker</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><affiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</affiliation></author><author><persName><forename type="first">Lawrence</forename><surname>Severt</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation></author><author><persName><forename type="first">Ann</forename><surname>Hunt</surname></persName><roleName type="degree">DO</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation></author><author><persName><forename type="first">Deborah</forename><surname>Raymond</surname></persName><roleName type="degree">MS</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation></author><author><persName><forename type="first">Laurie J.</forename><surname>Ozelius</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA</affiliation><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation></author><author><persName><forename type="first">Susan B.</forename><surname>Bressman</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><affiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-11-15"></date><biblScope unit="volume">25</biblScope><biblScope unit="issue">15</biblScope><biblScope unit="page" from="2536">2536</biblScope><biblScope unit="page" to="2541">2541</biblScope></imprint></monogr><idno type="istex">4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF</idno><idno type="DOI">10.1002/mds.23314</idno><idno type="ArticleID">MDS23314</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase. Small molecule kinase inhibitors have been developed for the treatment of certain cancers, and some antioncogenic agents such as sunitinib, may nonspecifically inhibit LRRK2. Few studies, however, have assessed cancer risk in LRRK2 mutation carriers. To explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients participating in genetic research. Charts were reviewed for 163 unrelated AJ PD patients, 31 of whom harbored the G2019S mutation. History of cancer was queried at baseline intake using a form reviewing medical conditions, and charts were reviewed for all follow‐up visits. 9/31 LRRK2 G2019S mutation carriers had nonskin cancers, whereas 15/132 without mutations had nonskin cancers, representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3–6.6). Age at first nonskin cancer was younger in the LRRK2 carriers (56.0 years) than the noncarriers (62.0 years), but was not significant. 67% of the LRRK2 carriers had their cancer before the onset of PD, whereas only 40% of noncarriers developed their first nonskin cancer before onset of PD. While further evaluation is warranted, our findings indicate an increased risk of nonskin cancers in LRRK2 G2019S mutation carriers, which may be related to toxic gain of function of mutated LRRK2. © 2010 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>genetics</term></item><item><term>Parkinson disease</term></item><item><term>LRRK2</term></item><item><term>cancer</term></item><item><term>search terms</term></item><item><term>Parkinson's disease</term></item><item><term>LRRK2</term></item><item><term>cancer</term></item><item><term>renal cancer</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-03-01">Received</change><change when="2010-05-26">Registration</change><change when="2010-11-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="150"><doi origin="wiley" registered="yes">10.1002/mds.v25:15</doi><numberingGroup><numbering type="journalVolume" number="25">25</numbering><numbering type="journalIssue">15</numbering></numberingGroup><coverDate startDate="2010-11-15">15 November 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="90" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.23314</doi><idGroup><id type="unit" value="MDS23314"></id></idGroup><countGroup><count type="pageTotal" number="6"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2010 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2010-03-01"></event><event type="manuscriptRevised" date="2010-04-29"></event><event type="manuscriptAccepted" date="2010-05-26"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:3.1.9 mode:FullText" date="2013-01-24"></event><event type="publishedOnlineEarlyUnpaginated" date="2010-09-03"></event><event type="publishedOnlineFinalForm" date="2010-11-10"></event><event type="firstOnline" date="2010-09-03"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-31"></event></eventGroup><numberingGroup><numbering type="pageFirst">2536</numbering><numbering type="pageLast">2541</numbering></numberingGroup><correspondenceTo>The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003.Department of Neurology, Beth Israel Medical Center, New York, NY, USA</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS23314.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="37"></count><count type="wordTotal" number="4522"></count></countGroup><titleGroup><title type="main" xml:lang="en"><i>LRRK2</i> G2019S mutations are associated with an increased cancer risk in Parkinson disease<link href="#fn2"></link></title><title type="short" xml:lang="en">Cancer in <fi>LRRK2</fi> PD</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2" corresponding="yes"><personName><givenNames>Rachel</givenNames><familyName>Saunders‐Pullman</familyName><degrees>MD, MPH</degrees></personName><contactDetails><email>rsaunder@bethisraelny.org</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Matthew J.</givenNames><familyName>Barrett</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Kaili M.</givenNames><familyName>Stanley</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Marta San</givenNames><familyName>Luciano</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Vicki</givenNames><familyName>Shanker</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Lawrence</givenNames><familyName>Severt</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Ann</givenNames><familyName>Hunt</familyName><degrees>DO</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Deborah</givenNames><familyName>Raymond</familyName><degrees>MS</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af3 #af4"><personName><givenNames>Laurie J.</givenNames><familyName>Ozelius</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Susan B.</givenNames><familyName>Bressman</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">genetics</keyword><keyword xml:id="kwd2">Parkinson disease</keyword><keyword xml:id="kwd3"><i>LRRK2</i></keyword><keyword xml:id="kwd4">cancer</keyword><keyword xml:id="kwd5">search terms</keyword><keyword xml:id="kwd6">Parkinson's disease</keyword><keyword xml:id="kwd7"><i>LRRK2</i></keyword><keyword xml:id="kwd8">cancer</keyword><keyword xml:id="kwd9">renal cancer</keyword></keywordGroup><fundingInfo><fundingAgency>National Institute of Neurological Disorders and Stroke</fundingAgency><fundingNumber>K23NS047256</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Michael J. Fox Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Thomas Hartman Foundation for Parkinson's Research</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Leucine rich repeat kinase (<i>LRRK2</i>) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase. Small molecule kinase inhibitors have been developed for the treatment of certain cancers, and some antioncogenic agents such as sunitinib, may nonspecifically inhibit <i>LRRK2</i>. Few studies, however, have assessed cancer risk in <i>LRRK2</i> mutation carriers. To explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients participating in genetic research. Charts were reviewed for 163 unrelated AJ PD patients, 31 of whom harbored the G2019S mutation. History of cancer was queried at baseline intake using a form reviewing medical conditions, and charts were reviewed for all follow‐up visits. 9/31 <i>LRRK2</i> G2019S mutation carriers had nonskin cancers, whereas 15/132 without mutations had nonskin cancers, representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3–6.6). Age at first nonskin cancer was younger in the <i>LRRK2</i> carriers (56.0 years) than the noncarriers (62.0 years), but was not significant. 67% of the <i>LRRK2</i> carriers had their cancer before the onset of PD, whereas only 40% of noncarriers developed their first nonskin cancer before onset of PD. While further evaluation is warranted, our findings indicate an increased risk of nonskin cancers in <i>LRRK2</i> G2019S mutation carriers, which may be related to toxic gain of function of mutated <i>LRRK2</i>. © 2010 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn2"><p>Potential conflict of interest: Nothing to report.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Cancer in LRRK2 PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>G2019S mutations are associated with an increased cancer risk in Parkinson disease</title></titleInfo><name type="personal"><namePart type="given">Rachel</namePart><namePart type="family">Saunders‐Pullman</namePart><namePart type="termsOfAddress">MD, MPH</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><affiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</affiliation><description>Correspondence: The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003.Department of Neurology, Beth Israel Medical Center, New York, NY, USA</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Matthew J.</namePart><namePart type="family">Barrett</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kaili M.</namePart><namePart type="family">Stanley</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marta San</namePart><namePart type="family">Luciano</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vicki</namePart><namePart type="family">Shanker</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><affiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lawrence</namePart><namePart type="family">Severt</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ann</namePart><namePart type="family">Hunt</namePart><namePart type="termsOfAddress">DO</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Deborah</namePart><namePart type="family">Raymond</namePart><namePart type="termsOfAddress">MS</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Laurie J.</namePart><namePart type="family">Ozelius</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA</affiliation><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Susan B.</namePart><namePart type="family">Bressman</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Beth Israel Medical Center, New York, New York, USA</affiliation><affiliation>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-11-15</dateIssued><dateCaptured encoding="w3cdtf">2010-03-01</dateCaptured><dateValid encoding="w3cdtf">2010-05-26</dateValid><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="tables">3</extent><extent unit="references">37</extent><extent unit="words">4522</extent></physicalDescription><abstract lang="en">Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase. Small molecule kinase inhibitors have been developed for the treatment of certain cancers, and some antioncogenic agents such as sunitinib, may nonspecifically inhibit LRRK2. Few studies, however, have assessed cancer risk in LRRK2 mutation carriers. To explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients participating in genetic research. Charts were reviewed for 163 unrelated AJ PD patients, 31 of whom harbored the G2019S mutation. History of cancer was queried at baseline intake using a form reviewing medical conditions, and charts were reviewed for all follow‐up visits. 9/31 LRRK2 G2019S mutation carriers had nonskin cancers, whereas 15/132 without mutations had nonskin cancers, representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3–6.6). Age at first nonskin cancer was younger in the LRRK2 carriers (56.0 years) than the noncarriers (62.0 years), but was not significant. 67% of the LRRK2 carriers had their cancer before the onset of PD, whereas only 40% of noncarriers developed their first nonskin cancer before onset of PD. While further evaluation is warranted, our findings indicate an increased risk of nonskin cancers in LRRK2 G2019S mutation carriers, which may be related to toxic gain of function of mutated LRRK2. © 2010 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: Nothing to report.</note><note type="funding">National Institute of Neurological Disorders and Stroke - No. K23NS047256; </note><note type="funding">Michael J. Fox Foundation</note><note type="funding">Thomas Hartman Foundation for Parkinson's Research</note><subject lang="en"><genre>Keywords</genre><topic>genetics</topic><topic>Parkinson disease</topic><topic>LRRK2</topic><topic>cancer</topic><topic>search terms</topic><topic>Parkinson's disease</topic><topic>LRRK2</topic><topic>cancer</topic><topic>renal cancer</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. 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