LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease
Identifieur interne : 000662 ( Main/Exploration ); précédent : 000661; suivant : 000663LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease
Auteurs : Rachel Saunders-Pullman [États-Unis] ; Matthew J. Barrett [États-Unis] ; Kaili M. Stanley [États-Unis] ; Marta San Luciano [États-Unis] ; Vicki Shanker [États-Unis] ; Lawrence Severt [États-Unis] ; Ann Hunt [États-Unis] ; Deborah Raymond [États-Unis] ; Laurie J. Ozelius [États-Unis] ; Susan B. Bressman [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2010-11-15.
English descriptors
- KwdEn :
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
Url:
DOI: 10.1002/mds.23314
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease</title><author><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name></author><author><name sortKey="Barrett, Matthew J" sort="Barrett, Matthew J" uniqKey="Barrett M" first="Matthew J." last="Barrett">Matthew J. Barrett</name></author><author><name sortKey="Stanley, Kaili M" sort="Stanley, Kaili M" uniqKey="Stanley K" first="Kaili M." last="Stanley">Kaili M. Stanley</name></author><author><name sortKey="Luciano, Marta San" sort="Luciano, Marta San" uniqKey="Luciano M" first="Marta San" last="Luciano">Marta San Luciano</name></author><author><name sortKey="Shanker, Vicki" sort="Shanker, Vicki" uniqKey="Shanker V" first="Vicki" last="Shanker">Vicki Shanker</name></author><author><name sortKey="Severt, Lawrence" sort="Severt, Lawrence" uniqKey="Severt L" first="Lawrence" last="Severt">Lawrence Severt</name></author><author><name sortKey="Hunt, Ann" sort="Hunt, Ann" uniqKey="Hunt A" first="Ann" last="Hunt">Ann Hunt</name></author><author><name sortKey="Raymond, Deborah" sort="Raymond, Deborah" uniqKey="Raymond D" first="Deborah" last="Raymond">Deborah Raymond</name></author><author><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name></author><author><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/mds.23314</idno><idno type="url">https://api.istex.fr/document/4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000227</idno><idno type="wicri:Area/Main/Curation">000189</idno><idno type="wicri:Area/Main/Exploration">000662</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease</title><author><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Barrett, Matthew J" sort="Barrett, Matthew J" uniqKey="Barrett M" first="Matthew J." last="Barrett">Matthew J. Barrett</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Stanley, Kaili M" sort="Stanley, Kaili M" uniqKey="Stanley K" first="Kaili M." last="Stanley">Kaili M. Stanley</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Luciano, Marta San" sort="Luciano, Marta San" uniqKey="Luciano M" first="Marta San" last="Luciano">Marta San Luciano</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Shanker, Vicki" sort="Shanker, Vicki" uniqKey="Shanker V" first="Vicki" last="Shanker">Vicki Shanker</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Severt, Lawrence" sort="Severt, Lawrence" uniqKey="Severt L" first="Lawrence" last="Severt">Lawrence Severt</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Hunt, Ann" sort="Hunt, Ann" uniqKey="Hunt A" first="Ann" last="Hunt">Ann Hunt</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Raymond, Deborah" sort="Raymond, Deborah" uniqKey="Raymond D" first="Deborah" last="Raymond">Deborah Raymond</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Mount Sinai School of Medicine, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></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 wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-11-15">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><idno type="ISSN">0885-3185</idno></series><idno type="istex">4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF</idno><idno type="DOI">10.1002/mds.23314</idno><idno type="ArticleID">MDS23314</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>LRRK2</term><term>Parkinson disease</term><term>Parkinson's disease</term><term>cancer</term><term>genetics</term><term>renal cancer</term><term>search terms</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml: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</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name></region><name sortKey="Barrett, Matthew J" sort="Barrett, Matthew J" uniqKey="Barrett M" first="Matthew J." last="Barrett">Matthew J. Barrett</name><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name><name sortKey="Bressman, Susan B" sort="Bressman, Susan B" uniqKey="Bressman S" first="Susan B." last="Bressman">Susan B. Bressman</name><name sortKey="Hunt, Ann" sort="Hunt, Ann" uniqKey="Hunt A" first="Ann" last="Hunt">Ann Hunt</name><name sortKey="Luciano, Marta San" sort="Luciano, Marta San" uniqKey="Luciano M" first="Marta San" last="Luciano">Marta San Luciano</name><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name><name sortKey="Raymond, Deborah" sort="Raymond, Deborah" uniqKey="Raymond D" first="Deborah" last="Raymond">Deborah Raymond</name><name sortKey="Saunders Ullman, Rachel" sort="Saunders Ullman, Rachel" uniqKey="Saunders Ullman R" first="Rachel" last="Saunders-Pullman">Rachel Saunders-Pullman</name><name sortKey="Severt, Lawrence" sort="Severt, Lawrence" uniqKey="Severt L" first="Lawrence" last="Severt">Lawrence Severt</name><name sortKey="Shanker, Vicki" sort="Shanker, Vicki" uniqKey="Shanker V" first="Vicki" last="Shanker">Vicki Shanker</name><name sortKey="Shanker, Vicki" sort="Shanker, Vicki" uniqKey="Shanker V" first="Vicki" last="Shanker">Vicki Shanker</name><name sortKey="Stanley, Kaili M" sort="Stanley, Kaili M" uniqKey="Stanley K" first="Kaili M." last="Stanley">Kaili M. Stanley</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000662 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000662 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:4E1E20E73CEAEFFCC57F06C461E7BE9F31AE8DFF
|texte= LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease
}}
| This area was generated with Dilib version V0.6.23. |  |