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Genetic parkinsonisms and cancer: a systematic review and meta-analysis

  • Andrea Sturchio ORCID logo , Alok K. Dwivedi ORCID logo , Joaquin A. Vizcarra , Martina Chirra , Elizabeth G. Keeling , Ignacio F. Mata , Marcelo A. Kauffman , Manoj K. Pandey , Giandomenico Roviello , Cristoforo Comi , Maurizio Versino , Luca Marsili ORCID logo EMAIL logo und Alberto J. Espay
Veröffentlicht/Copyright: 5. November 2020
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Reviews in the Neurosciences
Aus der Zeitschrift Reviews in the Neurosciences Band 32 Heft 2

Abstract

Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967–2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, SNCA was predominantly associated with gastrointestinal cancers, UCHL1 with breast cancer, and PRKN with head-and-neck cancers. In asymptomatic carriers, LRRK2 was predominantly associated with gastrointestinal and prostate cancers, PRKN with prostate and genitourinary tract cancers, GBA with sarcoma, and 22q11.2 deletion with leukemia. In symptomatic genetic parkinsonism, LRRK2 was associated with nonmelanoma skin cancers and breast cancers, and PRKN with head-and-neck cancers. Cancer was more often manifested in genetic parkinsonisms compared to asymptomatic carriers. These results suggest that intraindividual genetic contributions may modify the co-occurrence of cancer and neurodegeneration.

Keywords: cancer; genetic parkinsonism; LRRK2; meta-analysis; systematic review
Corresponding author: Luca Marsili, Gardner Family Center for Parkinson’s Disease and Movement Disorders, Department of Neurology, University of Cincinnati, 260 Stetson St., Cincinnati, OH45219, USA, E-mail:

  1. Author contribution: (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the first draft, B. Review and Critique. AS, JAV, MC, LM: 1A, 1B, 1C, 2A, 2B, 3AAKD: 1C, 2A, 2B, 2C, 3B EGK: 1C, 3B IFM, MAK, MP, GR, CC, MV: 3BAJE: 1A, 1B, 1C, 3B. All the co-authors listed above gave their final approval of this manuscript version.

  2. Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  3. Conflict of interest statement: The authors disclose no conflicts of interest regarding this manuscript.

  4. Availability of data and material: Drs. Marsili and Sturchio have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  5. Competing interests: Drs. Sturchio, Dwivedi, Vizcarra, Chirra, Keeling, and Marsili report no disclosures. Dr. Kauffman is an employee of the CONICET. He has received grant support from Ministry of Science and Technology of Argentina and Ministry of Health of Buenos Aires. Dr. Mata receives funding support from the Department of Veterans Affairs, National Institute of Health, Parkinson’s Disease Foundation, Michael J Fox Foundation, and American Parkinson Disease Association. Dr. Pandey has received the research grants from Alexion Pharmaceuticals (Boston, MA, USA) and Michael J. Fox Foundation (New YORK, NY, USA). He serves as Associate Editor of the Orphanet Journal of Rare Diseases (Springer Nature: Strassen, Luxembourg, LU) and act as reviewer for Nature Scientific Reports (Nature Publishing Group: London, London, GB), Journal of Reproductive Immunology (Elsevier Inc: New York, NY, US), The Journal of Reproductive Medicine (Science Printers and Publishers, Inc., St. Louis, MO, US), Journal of Innate Immunity (Karger Publishers (Switzerland): Basel, CH), Molecular Genetics and metabolism Reports (Elsevier Inc: New York, NY, US), Molecular Genetics and metabolism (Elsevier Inc: New York, NY, US), and PLOSone (Public Library of Science: San Francisco, CA, US) Dr. Roviello reports no disclosures Dr. Comi reports no disclosures Dr. Versino reports no disclosures Dr. Espay has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Adamas, Acadia, Acorda, InTrance, Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from USWorldMeds, Acadia, and Sunovion. He serves on the editorial boards of the Journal of Parkinson’s Disease, European Journal of Neurology, and JAMA Neurology.

References

Agalliu, I., Ortega, R.A., Luciano, M.S., Mirelman, A., Pont-Sunyer, C., Brockmann, K., Vilas, D., Tolosa, E., Berg, D., Warø, B., et al. (2019). Cancer outcomes among Parkinson’s disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson’s disease patients, and nonaffected controls. Mov. Disord. 34: 1392–1398, https://doi.org/10.1002/mds.27807.Suche in Google Scholar PubMed PubMed Central

Araki, M., Ito, G., and Tomita, T. (2018). Physiological and pathological functions of LRRK2: implications from substrate proteins. Neuronal Signaling 2: NS20180005, https://doi.org/10.1042/ns20180005.Suche in Google Scholar

Atashrazm, F. and Dzamko, N. (2016). LRRK2 inhibitors and their potential in the treatment of Parkinson’s disease: current perspectives. J. Clin. Pharmacol. 8: 177–189, https://doi.org/10.2147/cpaa.s102191.Suche in Google Scholar PubMed PubMed Central

Bajaj, A., Driver, J.A., and Schernhammer, E.S. (2010). Cancer Causes Control 21: 697, https://doi.org/10.1007/s10552-009-9497-6.Suche in Google Scholar PubMed

Becker, C., Brobert, G.P., Johansson, S., Jick, S.S., and Meier, C.R. (2010). Cancer risk in association with Parkinson disease: a population-based study. Park. Relat. Disord. 16: 186–190, https://doi.org/10.1016/j.parkreldis.2009.11.005.Suche in Google Scholar PubMed

Chen, Z., Cao, Z., Zhang, W., Gu, M., Zhou, Z.D., Li, B., Li, J., Tan, E.K., and Zeng, L. (2017). LRRK2 interacts with ATM and regulates Mdm2-p53 cell proliferation axis in response to genotoxic stress. Hum. Mol. Genet. 26: 4494–4505, https://doi.org/10.1093/hmg/ddx337.Suche in Google Scholar PubMed

Cui, X., Liew, Z., Hansen, J., Lee, P.C., Arah, O.A., and Ritz, B. (2019). Cancers preceding Parkinson’s disease after adjustment for bias in a Danish population-based case-control study. Neuroepidemiology 52: 136–143, https://doi.org/10.1159/000494292.Suche in Google Scholar PubMed PubMed Central

de Fost, M., Vom Dahl, S., Weverling, G.J., Brill, N., Brett, S., Häussinger, D., and Hollak, C.E. (2006). Increased incidence of cancer in adult Gaucher disease in Western Europe. Blood Cells Mol. Dis. 36: 53–58, https://doi.org/10.1016/j.bcmd.2005.08.004.Suche in Google Scholar PubMed

Deng, H., Wang, P., and Jankovic, J. (2018). The genetics of Parkinson disease. Ageing Res. Rev. 42: 72–85, https://doi.org/10.1016/j.arr.2017.12.007.Suche in Google Scholar PubMed

DerSimonian, R. and Laird, N. (2015). Meta-analysis in clinical trials revisited. Contemp. Clin. Trials 45: 139–45, https://doi.org/10.1016/j.cct.2015.09.002.Suche in Google Scholar PubMed PubMed Central

Devine, M.J., Plun-Favreau, H., and Wood, N.W. (2011). Parkinson’s disease and cancer: two wars, one front. Nat. Rev. Canc. 11: 812–823, https://doi.org/10.1038/nrc3150.Suche in Google Scholar PubMed

Espay, A.J., Vizcarra, J.A., Marsili, L., Lang, A.E., Simon, D.K., Merola, A., Josephs, K.A., Fasano, A., Morgante, F., Savica, R., et al. (2019). Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases. Neurology 92: 329–337, https://doi.org/10.1212/wnl.0000000000006926.Suche in Google Scholar

Espay, A.J., Brundin, P., and Lang, A.E. (2017). Precision medicine for disease modification in Parkinson disease. Nat. Rev. Neurol. 13: 119–126, https://doi.org/10.1038/nrneurol.2016.196.Suche in Google Scholar PubMed

Feng, D.D., Cai, W., and Chen, X. (2015). The associations between Parkinson’s disease and cancer: the plot thickens. Transl. Neurodegener. 4: 20, https://doi.org/10.1186/s40035-015-0043-z.Suche in Google Scholar PubMed PubMed Central

Freeman, M.F. and Tukey, J.W. (1950). Transformations related to the angular and the square root. Ann. Math. Stat. 21: 607–611, https://doi.org/10.1214/aoms/1177729756.Suche in Google Scholar

Ho, D.H., Seol, W., and Son, I. (2019). Upregulation of the p53-p21 pathway by G2019S LRRK2 contributes to the cellular senescence and accumulation of α-synuclein. Cell Cycle 18: 467–475, https://doi.org/10.1080/15384101.2019.1577666.Suche in Google Scholar PubMed PubMed Central

Hod, Y. (2004). Differential control of apoptosis by DJ-1 in prostate benign and cancer cells. J. Cell. Biochem. 92: 1221–1233, https://doi.org/10.1002/jcb.20159.Suche in Google Scholar PubMed

Hoehn, M.M. and Yahr, M.D. (1967). Parkinsonism: onset, progression and mortality. Neurology 17: 427–442, https://doi.org/10.1212/wnl.17.5.427.Suche in Google Scholar PubMed

Inzelberg, R. and Jankovic, J. (2007). Are Parkinson disease patients protected from some but not all cancers? Neurology 69: 1542–1550, https://doi.org/10.1212/01.wnl.0000277638.63767.b8.Suche in Google Scholar PubMed

Jansson, B. and Jankovic, J. (1985). Low cancer rates among patients with Parkinson’s disease. Ann. Neurol. 17: 505–509, https://doi.org/10.1002/ana.410170514.Suche in Google Scholar PubMed

Laman, H., Funes, J.M., Ye, H., Henderson, S., Galinanes-Garcia, L., Hara, E., Knowles, P., McDonald, N., and Boshoff, C. (2005). Transforming activity of Fbxo7 is mediated specifically through regulation of cyclin D/cdk6. EMBO J. 24: 3104–3116, https://doi.org/10.1038/sj.emboj.7600775.Suche in Google Scholar PubMed PubMed Central

Li, C.Y., Little, J.B., Hu, K., Zhang, W., Zhang, L., Dewhirst, M.W., and Huang, Q. (2001). Persistent genetic instability in cancer cells induced by non-DNA-damaging stress exposures. Canc. Res. 61: 428–432. 11212225.Suche in Google Scholar

Looyenga, B.D., Furge, K.A., Dykema, K.J., Koeman, J., Swiatek, P.J., Giordano, T.J., West, A.B., Resau, J.H., Teh, B.T., and MacKeigan, J.P. (2011). Chromosomal amplification of leucine-rich repeat kinase-2 (LRRK2) is required for oncogenic MET signaling in papillary renal and thyroid carcinomas. Proc. Natl. Acad. Sci. U.S.A. 108: 1439–1444, https://doi.org/10.1073/pnas.1012500108.Suche in Google Scholar PubMed PubMed Central

Mahajan, A.J., Chirra, M., Dwivedi, A.K., Sturchio, A., Keeling, E.G., Marsili, L., and Espay, A.J. (2020). Skin cancer may delay onset but not progression of Parkinson’s disease: a nested case-control study. Front. Neurol. 11: 406, https://doi.org/10.3389/fneur.2020.00406.Suche in Google Scholar PubMed PubMed Central

Matsuo, and Y. and Kamitani, T. (2010). Parkinson’s disease-related protein, alpha-synuclein, in malignant melanoma. PloS One 5: e10481, https://doi.org/10.1371/journal.pone.0010481.Suche in Google Scholar PubMed PubMed Central

Minami, Y., Yamamoto, R., Nishikouri, M., Fukao, A., and Hisamichi, S. (2000). Mortality and cancer in Parkinson’s disease. J. Neurol. 247: 429–434, https://doi.org/10.1007/s004150070171.Suche in Google Scholar PubMed

Moher, D., Liberati, A., Tetzlaff, J., and Altman, D.G. (2009). PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6: e1000097, https://doi.org/10.1371/journal.pmed.1000097.Suche in Google Scholar PubMed PubMed Central

Nozile, W.R., Nozile-Firth, K., Martinez-Ramirez, D., and Longo, M. (2018). Comment on: “cancer in Parkinson’s disease. Park. Relat. Disord. 53: 115. https://doi.org/10.1016/j.parkreldis.2018.05.004.Suche in Google Scholar PubMed

Obeso, J.A., Stamelou, M., Goetz, C.G., Poewe, W., Lang, A.E., Weintraub, D., Burn, D., Halliday, G.M., Bezard, E., Przedborski, S., et al. (2017). Past, present, and future of Parkinson’s disease: a special essay on the 200th anniversary of the Shaking Palsy. Mov. Disord. 32: 1264–1310, https://doi.org/10.1002/mds.27115.Suche in Google Scholar PubMed PubMed Central

Okochi-Takada, E., Nakazawa, K., Wakabayashi, M., Mori, A., Ichimura, S., Yasugi, T., and Ushijima, T. (2006). Silencing of the UCHL1 gene in human colorectal and ovarian cancers. Int. J. Canc. 119: 1338–1344, https://doi.org/10.1002/ijc.22025.Suche in Google Scholar PubMed

Ong, E.L., Goldacre, R., and Goldacre, M. (2014). Differential risks of cancer types in people with Parkinson’s disease: a national record-linkage study. Eur. J. Canc. 50: 2456–2462, https://doi.org/10.1016/j.ejca.2014.06.018.Suche in Google Scholar PubMed

Paquette, B., and Little, J.B. (1994). In vivo enhancement of genomic in-stability in minisatellite sequences of mouse C3H/10T1/2 cells transformed in vitro by X-rays. Canc. Res. 54: 3173–3178. 8205536.Suche in Google Scholar

Puschmann, A. (2017). New genes causing hereditary Parkinson’s disease or parkinsonism. Curr. Neurol. Neurosci. Rep. 17: 66, https://doi.org/10.1007/s11910-017-0780-8.Suche in Google Scholar

Reynolds, T.Y., Rockwell, S., and Glazer, P.M. (1996). Genetic instability induced by the tumor microenvironment. Canc. Res. 56: 5754–5757. 8971187.Suche in Google Scholar

Rojas, N.G., Cesarini, M., Etcheverry, J.L., Prat, G.A.D., Arciuch, V.A., and Gatto, E.M. (2020). Neurodegenerative diseases and cancer: sharing common mechanisms in complex interactions. J. Integr. Neurosci. 19: 187–199, https://doi.org/10.31083/j.jin.2020.01.3.Suche in Google Scholar

Saunders-Pullman, R., Mirelman, A., Alcalay, R.N., Wang, C., Ortega, R.A., Raymond, D., Mejia-Santana, H., Orbe-Reilly, M., Johannes, B.A., Thaler, A., et al. And the LRRK2 ashkenazi Jewish Consortium (2018). Progression in the LRRK2-asssociated Parkinson disease population. JAMA Neurology 75: 312–319.10.1001/jamaneurol.2017.4019Suche in Google Scholar

Sidransky, E. and Lopez, G. (2012). The link between the GBA gene and parkinsonism. Lancet Neurol. 11: 986–998, https://doi.org/10.1016/s1474-4422(12)70190-4.Suche in Google Scholar

Stroup, D.F., Berlin, J.A., Morton, S.C., Olkin, I., Williamson, G.D., Rennie, D., Moher, D., Becker, B.J., Sipe, T.A., and Thacker, S.B. (2000). Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. J. Am. Med. Assoc. 283, https://doi.org/10.1001/jama.283.15.2008, 2008–2012.Suche in Google Scholar PubMed

Veeriah, S., Taylor, B.S., Meng, S., Fang, F., Yilmaz, E., Vivanco, I., Janakiraman, M., Schultz, N., Hanrahan, A.J., Pao, W., et al. (2010). Somatic mutations of the Parkinson’s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat. Genet. 42: 77–82, https://doi.org/10.1038/ng.491.Suche in Google Scholar PubMed PubMed Central

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/revneuro-2020-0083).

Received: 2020-07-30
Accepted: 2020-09-20
Published Online: 2020-11-05
Published in Print: 2021-02-23

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Early life stress and brain plasticity: from molecular alterations to aberrant memory and behavior
  3. A review on preventive role of ketogenic diet (KD) in CNS disorders from the gut microbiota perspective
  4. Genetic parkinsonisms and cancer: a systematic review and meta-analysis
  5. Prevalence of sports-related spinal injury stratified by competition level and return to play guidelines
  6. The basal ganglia corticostriatal loops and conditional learning
  7. VEGF levels in patients with glioma: a systematic review and meta-analysis
  8. The therapeutic potential of mitochondrial transplantation for the treatment of neurodegenerative disorders
  9. CNS implications of COVID-19: a comprehensive review
  10. COVID-19 in age-related neurodegenerative diseases: is there a role for vitamin D3 as a possible therapeutic strategy?
https://doi.org/10.1515/revneuro-2020-0083
Schlagwörter für diesen Artikel
cancer; genetic parkinsonism; LRRK2; meta-analysis; systematic review

Artikel in diesem Heft

  1. Frontmatter
  2. Early life stress and brain plasticity: from molecular alterations to aberrant memory and behavior
  3. A review on preventive role of ketogenic diet (KD) in CNS disorders from the gut microbiota perspective
  4. Genetic parkinsonisms and cancer: a systematic review and meta-analysis
  5. Prevalence of sports-related spinal injury stratified by competition level and return to play guidelines
  6. The basal ganglia corticostriatal loops and conditional learning
  7. VEGF levels in patients with glioma: a systematic review and meta-analysis
  8. The therapeutic potential of mitochondrial transplantation for the treatment of neurodegenerative disorders
  9. CNS implications of COVID-19: a comprehensive review
  10. COVID-19 in age-related neurodegenerative diseases: is there a role for vitamin D3 as a possible therapeutic strategy?
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