LRRK2 Mutations and Cancer Risk

Objective/Rationale:             
Two groups have reported a possible association between carrying a LRRK2 mutation and non-skin cancers.  In order to determine whether this finding is present in a larger group, or whether specific factors in those populations account for the higher rate of cancer, a larger study from more locations, and with a larger group of Parkinson’s subjects and their family members is needed.  

Project Description: 
We will first evaluate information about history of cancer from four sites that have already collected such data: Beth Israel Medical Center in New York, Tel Aviv Medical Center, Sagol Neuroscience Center and the Chaim Sheba Medical Center  and the University Hospital Trondheim (Norway).  We will perform a pooled analysis and a meta-analysis.  Using information gleaned from this analysis, we will develop and administer a cancer screening questionnaire to a large group of people with Parkinson’s, and their family members. This will be from the following MJFF Consortium sites: the LRRK2 Ashkenazi Jewish Consortium sites of Tel Aviv, Columbia University and Beth Israel Medical Center (Drs. Giladi, Marder and Bressman, PI), the Hertie Institute (Tuebingen,Germany, Dr. Daniela Berg, PI), University Hospital at Barcelona (Barcelona, Spain, Dr. Eduardo Tolosa, PI), Trondheim (University Hospital, Trondheim, Norway, Dr. Jan Aasly , PI) and the PROGENI study group at the Indiana University (Dr. Tatiana Foroud, PI).

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
Melanoma is increased in Parkinson’s patients, and since this was definitively demonstrated, this has changed screening recommendations, and may have led to fewer deaths associated with melanoma in Parkinson’s patients.  The specter of possible increased cancer in LRRK2 mutation carriers necessitates a thorough evaluation of this possible association.  If one is demonstrated, this would change screening practices, and possibly treatments.

Anticipated Outcome:          
This study will help us to more definitively determine whether cancer is associated with LRRK2 mutation