The LRRK2 G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers.
OBJECTIVE
In view of the fact that cancer patterns in patients with Parkinson disease (PD) differ from the general population, we aimed to verify whether patients with PD with LRRK2 mutations have an increased risk for particular cancer types.


METHODS
In this cross-sectional study, eligible consenting Jewish patients with PD were genotyped for the predominant LRRK2 G2019S mutation. Oncologic data were obtained by personal interview and reviewing patients' files. Stepwise logistic regression was applied to model the probability of cancer occurrence in carriers vs noncarriers.


RESULTS
Overall, 79/490 (16.1%) genotyped patients carried the G2019S mutation. Seventy-seven (16%) were diagnosed with cancer; of those, 67 (14%) with a non-skin cancer. Eighteen (23%) carriers vs 49 (12%) noncarriers had a non-skin cancer (p = 0.01, odds ratio [OR] = 2.18, 95% confidence interval [CI] 1.19-3.99). A significant ethnicity effect was noted (p = 0.045, OR = 1.84, 95% CI 1.02-3.34). Among Ashkenazi patients, age and LRRK2 emerged as significant using stepwise logistic regression including age, gender, and LRRK2 status as explanatory variables. The OR for LRRK2 mutation carriers adjusted for age was 3.38 (95% CI 1.64-6.97, p = 0.0009).


CONCLUSIONS
Ashkenazi Jewish patients with PD who harbor the G2019S LRRK2 mutation are more likely to have a concomitant non-skin cancer than noncarriers.
Parkinson’s Disease and Movement Disorders Clinic, the Sagol Neuroscience Center, Department of Neurology, Israel. inzelber@post.tau.ac.il
R
R
Inzelberg
O S
OS
Cohen
J
J
Aharon-Peretz
I
I
Schlesinger
R
R
Gershoni-Baruch
R
R
Djaldetti
Z
Z
Nitsan
L
L
Ephraty
O
O
Tunkel
E
E
Kozlova
L
L
Inzelberg
N
N
Kaplan
T
T
Fixler Mehr
A
A
Mory
E
E
Dagan
E
E
Schechtman
E
E
Friedman
S
S
Hassin-Baer
D017668:Age of Onset; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007585:Jews; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009369:Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012737:Sex Factors; D016019:Survival Analysis
D000978:Antiparkinson Agents; D007980:Levodopa; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases