Parkinson’s Disease as a Risk Factor for Melanoma: A Review
Main Article Content
Keywords
melanoma, oncology, neurodegeneration, medical dermatology, parkinson's disease
Abstract
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.
References
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
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Creative Commons Attribution (CC BY): lets others distribute and copy the article, to create extracts, abstracts, and other revised versions, adaptations or derivative works of or from an article (such as a translation), to include in a collective work (such as an anthology), to text or data mine the article, even for commercial purposes, as long as they credit the author(s), do not represent the author as endorsing their adaptation of the article, and do not modify the article in such a way as to damage the author's honor or reputation.
Authors retain copyright in their work and license the publisher to publish the content. The publisher is the National Society for Cutaneous Medicine, with production and publishing support provided by OJS, Open Journal Systems,see https://pkp.sfu.
Prior to January 2022, authors transferred copyright to the National Society for Cutaneous Medicine. However, all articles are freely available to anyone in the world. There are no subscription fees, page charges, or article processing charges.
Zachary Monahan, US Navy
Zachary Monahan, MD, PhD
LT, MC, USN
Aaron Cantor, Walter Reed National Military Medical Center
Aaron S. Cantor, MD
LCDR, MC (FMF), USN
Dermatology Resident
Walter Reed National Military Medical Center
4494 Palmer Rd N, Bethesda, MD 20814
301-400-0466
Kent Handfield, Walter Reed National Military Medical Center
Kent Handfield, MD, FAAD, MPH
CDR (ret), MC, USN