RGD Reference Report - LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease. - Rat Genome Database

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LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease.

Authors: Saunders-Pullman, R  Barrett, MJ  Stanley, KM  Luciano, MS  Shanker, V  Severt, L  Hunt, A  Raymond, D  Ozelius, LJ  Bressman, SB 
Citation: Saunders-Pullman R, etal., Mov Disord. 2010 Nov 15;25(15):2536-41.
RGD ID: 5508410
Pubmed: PMID:20818610   (View Abstract at PubMed)
PMCID: PMC2978749   (View Article at PubMed Central)
DOI: DOI:10.1002/mds.23314   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cancer susceptibilityIAGP 5508410associated with Parkinson Disease and DNA:missense mutation:cds:p.G2019S (human)RGD 
cancer susceptibilityISOLRRK2 (Homo sapiens)5508410; 5508410associated with Parkinson Disease and DNA:missense mutation:cds:p.G2019S (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neoplasm susceptibilityIAGP 5508410associated with Parkinson Disease and DNA:missense mutation:cds:p.G2019SRGD 
Objects Annotated

Genes (Rattus norvegicus)
Lrrk2  (leucine-rich repeat kinase 2)

Genes (Mus musculus)
Lrrk2  (leucine-rich repeat kinase 2)

Genes (Homo sapiens)
LRRK2  (leucine rich repeat kinase 2)


Additional Information