Parkinson’s Disease as a Risk Factor for Melanoma: A Review

Main Article Content

Zachary Monahan
Aaron Cantor
Kent Handfield


melanoma, oncology, neurodegeneration, medical dermatology, parkinson's disease


Objective: To review the literature and place into a quantified context the relationship of Parkinson’s disease diagnosis to a subsequent diagnosis of malignant melanoma, and to briefly explore potential molecular associations between the two diseases.

Methods: The Medline database was queried with terms related to Parkinson’s disease (PD) and malignant melanoma, with use of Boolean operator AND to identify studies involving both diseases. Studies were divided into primary and meta-analyses, with exclusive evaluation of those quantifying risk of malignant melanoma after an established diagnosis of Parkinson’s disease. Critical studies were identified using Medline searches to identify established quantified risk metrics between classic melanoma risk factors and subsequent development of malignant melanoma.

Results: Twelve primary studies and three meta-analyses were evaluated and their risk metrices tabulated. Three studies offered estimated risk of development of malignant melanoma in patients with classic melanoma risk factors. These metrices were also tabulated and compared with the metrices established by the twelve primary studies. This demonstrated a similarity in overall risk of developing malignant melanoma in a patient with a diagnosis of Parkinson’s disease as compared to a patient with classical melanoma risk factors.

Limitations: Relatively few studies identified specifically quantified the classic risk factors for melanoma, and relatively few studies specifically quantified the degree of risk for developing melanoma after an established Parkinson’s disease diagnosis.

Conclusion: It is wise to consider the presence of Parkinson’s disease in a patient as one factor when clinicians decide on the appropriateness of regular full body screening examinations.


1. Driver JA, Logroscino G, Buring JE, Gaziano JM, Kurth T. A prospective cohort study of cancer incidence following the diagnosis of Parkinson’s disease. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1260-1265. doi:10.1158/1055-9965.EPI-07-0038

2. Bajaj A, Driver JA, Schernhammer ES. Parkinson’s disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control. 2010;21(5):697-707. doi:10.1007/s10552-009-9497-6

3. Sun L-M, Liang J-A, Chang S-N, Sung F-C, Muo C-H, Kao C-H. Analysis of Parkinson’s disease and subsequent cancer risk in Taiwan: a nationwide population-based cohort study. Neuroepidemiology. 2011;37(2):114-119. doi:10.1159/000331489

4. Schwid SR, Bausch J, Oakes D, et al. Cancer incidence in a trial of an antiapoptotic agent for Parkinson’s disease. Mov Disord. 2010;25(12):1801-1808. doi:10.1002/mds.23006

5. Becker C, Brobert GP, Johansson S, Jick SS, Meier CR. Cancer risk in association with Parkinson disease: a population-based study. Parkinsonism Relat Disord. 2010;16(3):186-190. doi:10.1016/j.parkreldis.2009.11.005

6. Lo RY, Tanner CM, Van Den Eeden SK, Albers KB, Leimpeter AD, Nelson LM. Comorbid cancer in Parkinson’s disease. Mov Disord. 2010;25(12):1809-1817. doi:10.1002/mds.23246

7. Bertoni JM, Arlette JP, Fernandez HH, et al. Increased melanoma risk in Parkinson disease: a prospective clinicopathological study. Arch Neurol. 2010;67(3):347-352. doi:10.1001/archneurol.2010.1

8. Constantinescu R, Romer M, Kieburtz K, DATATOP Investigators of the Parkinson Study Group. Malignant melanoma in early Parkinson’s disease: the DATATOP trial. Mov Disord. 2007;22(5):720-722. doi:10.1002/mds.21273

9. Constantinescu R, Elm J, Auinger P, et al. Malignant melanoma in early-treated Parkinson’s disease: the NET-PD trial. Mov Disord. 2014;29(2):263-265. doi:10.1002/mds.25734

10. Rugbjerg K, Friis S, Lassen CF, Ritz B, Olsen JH. Malignant melanoma, breast cancer and other cancers in patients with Parkinson’s disease. Int J Cancer. 2012;131(8):1904-1911. doi:10.1002/ijc.27443

11. Liu R, Gao X, Lu Y, Chen H. Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology. 2011;76(23):2002-2009. doi:10.1212/WNL.0b013e31821e554e

12. Ryu HJ, Park J-H, Choi M, et al. Parkinson’s Disease and Skin Cancer Risk: A Nationwide Population-Based Cohort Study in Korea. J Eur Acad Dermatol Venereol. Published online April 14, 2020. doi:10.1111/jdv.16462

13. Huang P, Yang X-D, Chen S-D, Xiao Q. The association between Parkinson’s disease and melanoma: a systematic review and meta-analysis. Transl Neurodegener. 2015;4:21. doi:10.1186/s40035-015-0044-y

14. Olsen JH, Friis S, Frederiksen K, McLaughlin JK, Mellemkjaer L, Møller H. Atypical cancer pattern in patients with Parkinson’s disease. Br J Cancer. 2005;92(1):201-205. doi:10.1038/sj.bjc.6602279

15. Kastner A, Hirsch EC, Lejeune O, Javoy-Agid F, Rascol O, Agid Y. Is the vulnerability of neurons in the substantia nigra of patients with Parkinson’s disease related to their neuromelanin content? J Neurochem. 1992;59(3):1080-1089. doi:10.1111/j.1471-4159.1992.tb08350.x

16. Gibb WR. Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson’s disease. Brain Res. 1992;581(2):283-291. doi:10.1016/0006-8993(92)90719-p

17. Haining R, Achat-Mendes C. Neuromelanin, one of the most overlooked molecules in modern medicine, is not a spectator. Neural Regen Res. 2017;12(3):372. doi:10.4103/1673-5374.202928

18. Jimbow K, Miyake Y, Homma K, et al. Characterization of melanogenesis and morphogenesis of melanosomes by physicochemical properties of melanin and melanosomes in malignant melanoma. Cancer Res. 1984;44(3):1128-1134.

19. Fedorow H, Tribl F, Halliday G, Gerlach M, Riederer P, Double K. Neuromelanin in human dopamine neurons: Comparison with peripheral melanins and relevance to Parkinson’s disease. Progress in Neurobiology. 2005;75(2):109-124. doi:10.1016/j.pneurobio.2005.02.001

20. Zecca L, Tampellini D, Gerlach M, Riederer P, Fariello RG, Sulzer D. Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour. MP, Mol Pathol. 2001;54(6):414-418.

21. Glasziou PP, Jones MA, Pathirana T, Barratt AL, Bell KJ. Estimating the magnitude of cancer overdiagnosis in Australia. Medical Journal of Australia. 2020;212(4):163-168. doi:10.5694/mja2.50455

22. Moller H, Mellemkjaer L, McLaughlin JK, Olsen JH. Occurrence of different cancers in patients with Parkinson’s disease. BMJ. 1995;310(6993):1500-1501. doi:10.1136/bmj.310.6993.1500

23. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(4):429-435. doi:10.1001/jama.2016.8465

24. Hübner J, Waldmann A, Eisemann N, et al. Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening: European Journal of Cancer Prevention. 2018;27(6):563-569. doi:10.1097/CEJ.0000000000000392

25. Cho E, Rosner BA, Feskanich D, Colditz GA. Risk factors and individual probabilities of melanoma for whites. J Clin Oncol. 2005;23(12):2669-2675. doi:10.1200/JCO.2005.11.108

26. Cho E, Rosner BA, Colditz GA. Risk factors for melanoma by body site. Cancer Epidemiol Biomarkers Prev. 2005;14(5):1241-1244. doi:10.1158/1055-9965.EPI-04-0632

27. Rigel DS. Epidemiology of melanoma. Semin Cutan Med Surg. 2010;29(4):204-209. doi:10.1016/j.sder.2010.10.005

28. Olsen CM, Pandeya N, Thompson BS, et al. Risk Stratification for Melanoma: Models Derived and Validated in a Purpose-Designed Prospective Cohort. J Natl Cancer Inst. 2018;110(10):1075-1083. doi:10.1093/jnci/djy023

29. Goldberg MS, Doucette JT, Lim HW, Spencer J, Carucci JA, Rigel DS. Risk factors for presumptive melanoma in skin cancer screening: American Academy of Dermatology National Melanoma/Skin Cancer Screening Program experience 2001-2005. J Am Acad Dermatol. 2007;57(1):60-66. doi:10.1016/j.jaad.2007.02.010

30. Beaulieu D, Tsao H, Michaud DS, Okhovat J-P, Halpern AC, Geller AC. Factors associated with suspected nonmelanoma skin cancers, dysplastic nevus, and cutaneous melanoma among first-time SPOTme screening program participants (2009-2010). Journal of the American Academy of Dermatology. Published online December 2018:S0190962218330524. doi:10.1016/j.jaad.2018.12.010

31. Potjer TP, Bollen S, Grimbergen AJEM, et al. Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non‐ CDKN2A/CDK4 melanoma families. Int J Cancer. 2019;144(10):2453-2464. doi:10.1002/ijc.31984

32. Li YI, Wong G, Humphrey J, Raj T. Prioritizing Parkinson’s disease genes using population-scale transcriptomic data. Nat Commun. 2019;10(1):994. doi:10.1038/s41467-019-08912-9

33. Dalvin LA, Damento GM, Yawn BP, Abbott BA, Hodge DO, Pulido JS. Parkinson Disease and Melanoma: Confirming and Reexamining an Association. Mayo Clin Proc. 2017;92(7):1070-1079. doi:10.1016/j.mayocp.2017.03.014

34. Turriani E, Lázaro DF, Ryazanov S, et al. Treatment with diphenyl-pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death. Proc Natl Acad Sci USA. 2017;114(25):E4971-E4977. doi:10.1073/pnas.1700200114

35. Kasten M, Klein C. The many faces of alpha-synuclein mutations: The Many Faces of Alpha-Synuclein Mutations. Mov Disord. 2013;28(6):697-701. doi:10.1002/mds.25499

36. de Oliveira GAP, Silva JL. Alpha-synuclein stepwise aggregation reveals features of an early onset mutation in Parkinson’s disease. Commun Biol. 2019;2:374. doi:10.1038/s42003-019-0598-9

37. Rodriguez-Leyva I, Chi-Ahumada E, Mejía M, et al. The Presence of Alpha-Synuclein in Skin from Melanoma and Patients with Parkinson’s Disease. Mov Disord Clin Pract. 2017;4(5):724-732. doi:10.1002/mdc3.12494

38. Shimura H, Hattori N, Kubo S i, et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000;25(3):302-305. doi:10.1038/77060

39. Li N, Wang L, Zhang J, et al. Whole-exome sequencing in early-onset Parkinson’s disease among ethnic Chinese. Neurobiol Aging. 2020;90:150.e5-150.e11. doi:10.1016/j.neurobiolaging.2019.12.023

40. Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392(6676):605-608. doi:10.1038/33416

41. Hu H-H, Kannengiesser C, Lesage S, et al. PARKIN Inactivation Links Parkinson’s Disease to Melanoma. J Natl Cancer Inst. 2016;108(3). doi:10.1093/jnci/djv340

42. Lee YS, Jung YY, Park MH, et al. Deficiency of parkin suppresses melanoma tumor development and metastasis through inhibition of MFN2 ubiquitination. Cancer Lett. 2018;433:156-164. doi:10.1016/j.canlet.2018.07.007

43. Pan T, Li X, Jankovic J. The association between Parkinson’s disease and melanoma: Association between PD and Melanoma. Int J Cancer. 2011;128(10):2251-2260. doi:10.1002/ijc.25912

44. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-954. doi:10.1038/nature00766

45. Smith WW, Pei Z, Jiang H, Dawson VL, Dawson TM, Ross CA. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat Neurosci. 2006;9(10):1231-1233. doi:10.1038/nn1776

46. Di Fonzo A, Rohé CF, Ferreira J, et al. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet. 2005;365(9457):412-415. doi:10.1016/S0140-6736(05)17829-5

47. Zondler L, Miller-Fleming L, Repici M, et al. DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson’s disease. Cell Death Dis. 2014;5:e1350. doi:10.1038/cddis.2014.307

48. Chien C-H, Lee M-J, Liou H-C, Liou H-H, Fu W-M. Local immunosuppressive microenvironment enhances migration of melanoma cells to lungs in DJ-1 knockout mice. PLoS ONE. 2015;10(2):e0115827. doi:10.1371/journal.pone.0115827

49. Narendra DP, Jin SM, Tanaka A, et al. PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin. Green DR, ed. PLoS Biol. 2010;8(1):e1000298. doi:10.1371/journal.pbio.1000298

50. O’Flanagan CH, Morais VA, Wurst W, De Strooper B, O’Neill C. The Parkinson’s gene PINK1 regulates cell cycle progression and promotes cancer-associated phenotypes. Oncogene. 2015;34(11):1363-1374. doi:10.1038/onc.2014.81