The
            <i>LRRK2</i>
            G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers

Inzelberg, Rivka; Cohen, Ohad; Aharon‐Peretz, Judith; Schlesinger, Ilana; Gershoni‐Baruch, Ruth; Djaldetti, Ruth; Nitsan, Zeev; Ephraty, Lilach; Tunkel, Olga; Kozlova, Evgenia; Inzelberg, Lilah; Kaplan, N.; Mehr, Tariq; Mory, Adi; Dagan, Efrat; Schechtman, Edna; Friedman, Eitan; Hassin‐Baer, Sharon

doi:10.1212/wnl.0b013e318249f673

Cited by 59 publications

(64 citation statements)

References 32 publications

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“…Recently, LRRK2 mutations have been found to be an important risk factor for sporadic and familial PD [24,25]. It has been shown that PD patients with LRRK2 mutations have a different profile of malignancy compared with non-carriers of LRRK2 gene mutations [26,27]. Mutation carriers had a particularly increased risk of breast cancer in both studies, and might explain part of the increased rate in breast cancer in PD patients that we and others find [2,3].…”

Section: Interpretation and Implicationssupporting

confidence: 51%

Differential risks of cancer types in people with Parkinson’s disease: A national record-linkage study

Ong

Goldacre

2014

European Journal of Cancer

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Section: Interpretation and Implicationssupporting

confidence: 51%

Differential risks of cancer types in people with Parkinson’s disease: A national record-linkage study

Ong

Goldacre

2014

European Journal of Cancer

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“…Finally, we did not have information on hormonal and reproductive factors that could confound the association between LRRK2 mutations and breast cancer. Although we did not have complete information on the BRCA1/BRCA2 mutation status of all women with PD, investigators at Sheba Medical Center 19 evaluated mutations in their breast cancer cases and found only a single BRCA1 mutation that cosegregated with the LRRK2 G2019S mutation. They separately analyzed genome-wide association study data evaluating breast cancer single-nucleotide polymorphisms in relationship to PD genes and found no suggestion of simple cosegregation or shared genetic loci 31 .…”

Section: Discussionmentioning

confidence: 99%

“…Sinai Beth Israel Medical Center, New York). Detailed descriptions about study participants, data collection, LRRK2 genotyping and cancer outcomes for three of the centers have been published 19,20,22,23 and are summarized for all five centers in the eTable in the Supplement. Briefly, at all centers, PD patients were queried regarding demographic and lifestyle factors as well as, personal and family history of PD and other diseases, including self-reported cancer, type of cancer, and age at diagnosis.…”

Section: Methodsmentioning

confidence: 99%

Higher Frequency of Certain Cancers inLRRK2G2019S Mutation Carriers With Parkinson Disease

et al. 2015

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disease (PD) who harbor LRRK2 G2019S mutations may have increased risks of nonskin cancers. However, the results have been inconsistent across studies.OBJECTIVES To analyze pooled data from 5 centers to further examine the association between LRRK2 G2019S mutation and cancer among patients with PD and to explore factors that could explain discrepancies. DESIGN, SETTING, AND PARTICIPANTS Clinical, demographic, and genotyping data as well as cancer outcomes were pooled from 1549 patients with PD recruited across 5 movement disorders clinics located in Europe, Israel, and the United States. Associations between LRRK2 G2019S mutation and the outcomes were examined using mixed-effects logistic regression models to estimate odds ratios (ORs) and 95% CIs. Models were adjusted for age and ethnicity (Ashkenazi Jewish vs others) as fixed effects and study center as a random effect. MAIN OUTCOMES AND MEASURESAll cancers combined, nonskin cancers, smoking-related cancers, hormone-related cancers, and other types of cancer. RESULTSThe overall prevalence of the LRRK2 G2019S mutation was 11.4% among all patients with PD. Mutation carriers were younger at PD diagnosis and more likely to be women (53.1%) and of Ashkenazi Jewish descent (76.8%) in comparison with individuals who were not mutation carriers. The LRRK2 G2019S mutation carriers had statistically significant increased risks for nonskin cancers (OR, 1.62; 95% CI, 1.04-2.52), hormone-related cancers (OR, 1.87; 95% CI, 1.07-3.26) and breast cancer (OR, 2.34; 95% CI, 1.05-5.22) in comparison with noncarriers. There were no associations with other cancers. There were no major statistically significant differences in the results when the data were stratified by Ashkenazi Jewish ethnicity; however, there was some evidence of heterogeneity across centers.CONCLUSIONS AND RELEVANCE This multinational study from 5 centers demonstrates that LRRK2 G2019S mutation carriers have an overall increased risk of cancer, especially for hormone-related cancer and breast cancer in women. Larger prospective cohorts or family-based studies investigating associations between LRRK2 mutations and cancer among patients with PD are warranted to better understand the underlying genetic susceptibility between PD and hormone-related cancers.

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“…Although indirect or controversial reports about the association of PD and cancer [15,16,25,26], diabetes mellitus patients still have a potential risk for PD [11,12], and the cancer risk among PD patients may be also attributed to the prescribing medicines for PD, as the story in diabetes mellitus. This gave hint us to think of the relation of DAs to cancer, in addition to their adverse effects on treatment of PD.…”

Section: Discussionmentioning

confidence: 99%

“…Recently cancer risk among the PD patients gained much attention, especially for those with a genetic linkage [15,16], and the role of parkin, the E3 ubiquitin ligase, in cancers [17]. Therefore it is nothing to be surprised at the possibility of cross-talking between neurodegeneration and neoplasms.…”

Section: Introductionmentioning

confidence: 99%

Cancer risks among the users of ergot-derived dopamine agonists for Parkinson's disease, a nationwide population-based survey

Wang¹,

Chao²,

Hsieh³

et al. 2015

Parkinsonism & Related Disorders

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The LRRK2 G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers

Abstract: Ashkenazi Jewish patients with PD who harbor the G2019S LRRK2 mutation are more likely to have a concomitant non-skin cancer than noncarriers.

Cited by 59 publications

References 32 publications

Differential risks of cancer types in people with Parkinson’s disease: A national record-linkage study

Differential risks of cancer types in people with Parkinson’s disease: A national record-linkage study

Higher Frequency of Certain Cancers inLRRK2G2019S Mutation Carriers With Parkinson Disease

Cancer risks among the users of ergot-derived dopamine agonists for Parkinson's disease, a nationwide population-based survey

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