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Circulating Melatonin Levels: Possible Link Between Parkinson’s Disease and Cancer Risk?

  • Special Section on Cancer and Rhythm
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Abstract

Lower rates of cancer mortality/incidence in patients with Parkinson’s disease (PD) have given rise to speculations about risk or preventative factors common to both diseases, including life-style factors (such as smoking) and genetic susceptibility. Melatonin, a hormone known for its sleep regulatory effects, may play an important role in carcinogenesis as suggested by substantial laboratory and less direct epidemiologic evidence. Particularly, a reduction in melatonin, such as experienced by persons who are exposed to light at night, appears to increase cancer risk. Variations in melatonin levels have been linked to PD in several different ways. Some studies show higher morning melatonin levels in PD patients than in healthy controls. One could speculate that the sleep disorders that affect almost two thirds of those suffering from PD and can precede PD motor symptoms by several years may be associated with variations in melatonin levels. Moreover, in animal models, interventions that increase the bioavailability of melatonin appears to increase the severity of parkinsonian symptoms, whereas reduction in melatonin by pinealectomy or exposure to bright light can enhance recovery from parkinsonisms symptoms. Finally, preliminary epidemiological evidence suggests that longer years of working night shifts is associated with a reduced risk of PD among participants of the Nurses’ Health Study (NHS), whereas longer hours of sleep appear to increase their risk. In sum, while lower melatonin concentrations may predict a higher cancer risk, there is also some evidence that they may be associated with a lower risk of PD. We therefore hypothesize that elevated circulating melatonin levels in PD patients may contribute to their lower cancer rates.

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References

  1. Barbeau A, KJoly JG (1963) Parkinsonism et cancer. Union Med Can 92:169–174

    CAS  PubMed  Google Scholar 

  2. Ben-Shlomo Y, Marmot MG (1995) Survival and cause of death in a cohort of patients with parkinsonism: possible clues to aetiology? J Neurol Neurosurg Psychiatry 58:293–299

    CAS  PubMed  Google Scholar 

  3. Gorell JM, Johnson CC, Rybicki BA (1994) Parkinson’s disease and its comorbid disorders: an analysis of Michigan mortality data, 1970 to 1990. Neurology 44:1865–1868

    CAS  PubMed  Google Scholar 

  4. Harada H, Nishikawa S, Takahashi K (1983) Epidemiology of Parkinson’s disease in a Japanese city. Arch Neurol 40:151–154

    CAS  PubMed  Google Scholar 

  5. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression, and mortality. 1967.Neurology 57:S11–S26

    Google Scholar 

  6. Jansson B, Jankovic J (1985) Low cancer rates among patients with Parkinson’s disease. Ann Neurol 17:505–509

    Article  CAS  PubMed  Google Scholar 

  7. Pritchard PBr, Netsky MG (1973) Prevalence of neoplasms and causes of death in paralysis agitans. A necropsy study.Neurology 23:215–222

    PubMed  Google Scholar 

  8. Rajput AH, Offord KP, Beard CM, Kurland LT (1987) A case-control study of smoking habits, dementia, and other illnesses in idiopathic Parkinson’s disease. Neurology 37:226–232

    CAS  PubMed  Google Scholar 

  9. Westlund K (1956) Cancer as a cause of death among patients with other chronic diseases. JAMA 162:1003

    Google Scholar 

  10. Minami Y, Yamamoto R, Nishikouri M, Fukao A, Hisamichi S (2000) Mortality and cancer incidence in patients with Parkinson’s disease.J Neurol 247:429–434

    Article  CAS  PubMed  Google Scholar 

  11. Elbaz A, Peterson BJ, Yang P, et al. (2002) Nonfatal cancer preceding Parkinson’s disease: a case-control study. Epidemiology 13:157–164

    Article  PubMed  Google Scholar 

  12. Rostami-Hodjegan ALM, Woods HF, Tucker GT (1998) Meta-analysis of studies of the CYP2D6 polymorphism in relation to lung cancer and Parkinson’s disease. Pharmacogenetics 8:227–238

    CAS  PubMed  Google Scholar 

  13. Morens DM GA, Davis JW, Ross GW, White LR, Reed D (1996) Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease.Am J Epidemiol 144:400–404

    CAS  PubMed  Google Scholar 

  14. Elbaz A, Bower JH, Peterson BJ, et al. (2003) Survival study of Parkinson disease in Olmsted County, Minnesota. Arch Neurol 60:91–96

    PubMed  Google Scholar 

  15. Vanacore N, Spila-Alegiani S, Raschetti R, Meco G (1999) Mortality cancer risk in parkinsonian patients: a population-based study.Neurology 52:395–398

    CAS  PubMed  Google Scholar 

  16. Olsen JH, Friis S, Frederiksen K, McLaughlin JK, Mellemkjaer L, Moller H (2005) Atypical cancer pattern in patients with Parkinson’s disease. Br J Cancer 92:201–205

    Article  CAS  PubMed  Google Scholar 

  17. Jenner P (1998) Oxidative mechanisms in nigral cell death in Parkinson’s disease. Mov Disord 13:24–34

    PubMed  Google Scholar 

  18. Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53:S26–S36

    Article  CAS  PubMed  Google Scholar 

  19. Zhang SM, Hernan MA, Chen H, Spiegelman D, Willett WC, Ascherio A (2002) Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk. Neurology 59:1161–1169

    CAS  PubMed  Google Scholar 

  20. Leon J, Acuna-Castroviejo D, Sainz RM, Mayo JC, Tan DX, Reiter RJ (2004) Melatonin and mitochondrial function. Life Sci 75:765–790

    Article  CAS  PubMed  Google Scholar 

  21. Mayo JC, Sainz RM, Uria H, Antolin I, Esteban MM, Rodriguez C (1998) Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells: implications for Parkinson’s disease.J Pineal Res 24:179–192

    CAS  PubMed  Google Scholar 

  22. Reiter RJ, Guerrero JM, Escames G, Pappolla MA, Acuna-Castroviejo D (1997) Prophylactic actions of melatonin in oxidative neurotoxicity. Ann N Y Acad Sci 825:70–78

    CAS  PubMed  Google Scholar 

  23. Reiter RJ, Tan DX, Mayo JC, Sainz RM, Leon J, Czarnocki Z (2003) Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochim Pol 50:1129–1146

    CAS  PubMed  Google Scholar 

  24. Absi E, Ayala A, Machado A, Parrado J (2000) Protective effect of melatonin against the 1-methyl−4-phenylpyridinium-induced inhibition of complex I of the mitochondrial respiratory chain. J Pineal Res 29:40–47

    Article  CAS  PubMed  Google Scholar 

  25. Dabbeni-Sala F, Di Santo S, Franceschini D, Skaper SD, Giusti P (2001) Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity. FASEB J 15:164–170

    Article  CAS  PubMed  Google Scholar 

  26. Khaldy H, Escames G, Leon J, Vives F, Luna JD, Acuna-Castroviejo D (2000) Comparative effects of melatonin, L-deprenyl, Trolox and ascorbate in the suppression of hydroxyl radical formation during dopamine autoxidation in vitro. J Pineal Res 29:100–107

    Article  CAS  PubMed  Google Scholar 

  27. Acuna-Castroviejo D, Coto-Montes A, Gaia Monti M, Ortiz GG, Reiter RJ (1997) Melatonin is protective against MPTP-induced striatal and hippocampal lesions. Life Sci 60:PL23–PL29

    CAS  PubMed  Google Scholar 

  28. Antolin I, Mayo JC, Sainz RM, et al. (2002) Protective effect of melatonin in a chronic experimental model of Parkinson’s disease. Brain Res 943:163–173

    CAS  PubMed  Google Scholar 

  29. Coulom H, Birman S (2004) Chronic exposure to rotenone models sporadic Parkinson’s disease in Drosophila melanogaster. J Neurosci 24:10993–10998

    Article  CAS  PubMed  Google Scholar 

  30. Jin BK, Shin DY, Jeong MY, et al. (1998) Melatonin protects nigral dopaminergic neurons from 1-methyl−4-phenylpyridinium (MPP+) neurotoxicity in rats. Neurosci Lett 245:61–64

    Article  CAS  PubMed  Google Scholar 

  31. Thomas B, Mohanakumar KP (2004) Melatonin protects against oxidative stress caused by 1-methyl−4-phenyl−1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. J Pineal Res 36:25–32

    Article  CAS  PubMed  Google Scholar 

  32. Morgan WW, Nelson JF (2001) Chronic administration of pharmacological levels of melatonin does not ameliorate the MPTP-induced degeneration of the nigrostriatal pathway.Brain Res 921:115–121

    Article  CAS  PubMed  Google Scholar 

  33. van der Schyf CJ, Castagnoli K, Palmer S, Hazelwood L, Castagnoli NJ (2000) Melatonin fails to protect against long-term MPTP-induced dopamine depletion in mouse striatum.Neurotox Res 1:261–269

    PubMed  Google Scholar 

  34. Willis GL, Armstrong SM (1999) A therapeutic role for melatonin antagonism in experimental models of Parkinson’s disease. Physiol Behav 66:786–795

    Article  Google Scholar 

  35. Catala MD, Canete-Nicolas C, Iradi A, Tarazona PJ, Tormos JM, Pascual-Leone A (1997) Melatonin levels in Parkinson’s disease: drug therapy versus electrical stimulation of the internal globus pallidus. Exp Gerontol 32:553–558

    CAS  PubMed  Google Scholar 

  36. Willis GL, Armstrong SM (1999) A therapeutic role for melatonin antagonism in experimental models of Parkinson’s disease.Physiol Behav 66:785–795

    Article  CAS  PubMed  Google Scholar 

  37. Zisapel N (2001) Melatonin-dopamine interactions: from basic neurochemistry to a clinical setting. Cell Mol Neurobiol 21:605–616

    Article  CAS  PubMed  Google Scholar 

  38. Cos S, Fernandez F, Sanchez-Barcelo EJ (1996) Melatonin inhibits DNA synthesis in MCF−7 human breast cancer cells in vitro. Life Sci 58:2447–2453

    CAS  PubMed  Google Scholar 

  39. Cos S, Fernandez R, Guezmes A, Sanchez-Barcelo EJ (1998) Influence of melatonin on invasive and metastatic properties of MCF−7 human breast cancer cells. Cancer Res 58:4383–4390

    CAS  PubMed  Google Scholar 

  40. Cos S, Mediavilla MD, Fernandez R, Gonzalez-Lamuno D, Sanchez-Barcelo EJ (2002) Does melatonin induce apoptosis in MCF−7 human breast cancer cells in vitro? J Pineal Res 32:90–96

    Article  CAS  PubMed  Google Scholar 

  41. Hill SM, Blask DE (1988) Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF−7) in culture. Cancer Res 48:6121–6126

    CAS  PubMed  Google Scholar 

  42. Kanishi Y, Kobayashi Y, Noda S, Ishizuka B, Saito K (2000) Differential growth inhibitory effect of melatonin on two endometrial cancer cell lines. J Pineal Res 28:227–233

    Article  CAS  PubMed  Google Scholar 

  43. Mediavilla MD, Cos S, Sanchez-Barcelo EJ (1999) Melatonin increases p53 and p21WAF1 expression in MCF−7 human breast cancer cells in vitro. Life Sci 65:415–420

    Article  CAS  PubMed  Google Scholar 

  44. Petranka J, Baldwin WS, Bierman J, Jayadev S, Barrett JC, Murphy E (1999) The oncostatic action of melatonin in an ovarian carcinoma cell line. Pineal Res 26:129–136

    CAS  Google Scholar 

  45. Shiu SY, Li L, Xu JN, Pang CS, Wong JT, Pang SF (1999) Melatonin-induced inhibition of proliferation and G1/S cell cycle transition delay of human choriocarcinoma JAr cells: possible involvement of MT2 (MEL1B) receptor. Pineal Res 27:183–192

    CAS  Google Scholar 

  46. Sze SF, Ng TB, Liu WK (1993) Antiproliferative effect of pineal indoles on cultured tumor cell lines. J Pineal Res 14:27–33

    CAS  PubMed  Google Scholar 

  47. Ying SW, Niles LP, Crocker C (1993) Human malignant melanoma cells express high-affinity receptors for melatonin: antiproliferative effects of melatonin and 6-chloromelatonin. Eur J Pharmacol 246:89–96

    CAS  PubMed  Google Scholar 

  48. Tamarkin L, Cohen M, Roselle D, Reichert C, Lippman M, Chabner B (1981) Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat. Cancer Res 41:4432–4436

    CAS  PubMed  Google Scholar 

  49. Musatov SA, Anisimov VN, Andre V, Vigreux C, Godard T, Sichel F (1999) Effects of melatonin on N-nitroso-N-methylurea-induced carcinogenesis in rats and mutagenesis in vitro (Ames test and COMET assay).Cancer Lett 138:37–44

    Article  CAS  PubMed  Google Scholar 

  50. Anisimov VN, Popovich IG, Zabezhinski MA (1997) Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats. Carcinogenesis 18:1549–1553

    Article  CAS  PubMed  Google Scholar 

  51. Anisimov VN, Kvetnoy IM, Chumakova NK, et al. (1999) Melatonin and colon carcinogenesis. Exp Toxicol Pathol 51:47–52

    CAS  PubMed  Google Scholar 

  52. Cini G, Coronnello M, Mini E, Neri B (1998) Melatonin’s growth-inhibitory effect on hepatoma AH 130 in the rat. Cancer Lett 125:51–59

    Article  CAS  PubMed  Google Scholar 

  53. Mocchegiani E, Perissin L, Santarelli L, et al. (1999) Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL−2. Int J Immunopharmacol 21:27–46

    CAS  PubMed  Google Scholar 

  54. Brzezinski A (1997) Melatonin in humans. N Engl J Med 336:186–195

    Article  CAS  PubMed  Google Scholar 

  55. Blask DE, Dauchy RT, Sauer LA, Krause JA, Brainard GC (2002) Light during darkness, melatonin suppression and cancer progression. Neuroendocrinol Lett 23:52–56

    PubMed  Google Scholar 

  56. Dauchy RT, Blask DE, Sauer LA, Brainard GC, Krause JA (1999) Dim light during darkness stimulates tumor progression by enhancing tumor fatty acid uptake and metabolism. Cancer Letters 144:131–136

    Article  CAS  PubMed  Google Scholar 

  57. Vijayalaxmi, Thomas CRJ, Reiter RJ, Herman TS (2002) Melatonin: from basic research to cancer treatment clinics. J Clin Oncol 20:2575–2601

    Article  CAS  PubMed  Google Scholar 

  58. Schernhammer ES, Hankinson SE (2003) Light at night: a novel risk factor for cancer in shift workers? Clin Occupational Environment Med 3:263–278

    Google Scholar 

  59. Snyder SH, Axelrod J, Zweig M (1967) Circadian rhythm in the serotonin content of the rat pineal gland: regulating factors. J Pharmacol Exp Ther 158:206–213

    CAS  PubMed  Google Scholar 

  60. Zeitzer JM, Dijk DJ, Kronauer R, Czeisler C (2000) Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. J Physiol 526:695–702

    CAS  PubMed  Google Scholar 

  61. Graham C, Cook MR (2001) Examination of the melatonin hypothesis in women exposed at night to EMF or bright light. Environ Health Perspect 109:501–507

    CAS  PubMed  Google Scholar 

  62. Davis S, Mirick DK, Stevens RG (2001) Night shift work, light at night, and risk of breast cancer. J Natl Cancer Inst 93:1557–1562

    CAS  PubMed  Google Scholar 

  63. Hansen J (2001) Increased breast cancer risk among women who work predominantly at night. Epidemiology 12:74–77

    Article  CAS  PubMed  Google Scholar 

  64. Pukkala E, Auvinen H, Wahlberg G (1995) Incidence of cancer among Finnish airline cabin attendants. BMJ 311:649–652

    CAS  PubMed  Google Scholar 

  65. Rafnsson V, Tulinius H, Jonasson JG, Hrafnkelsson J (2001) Risk of breast cancer in female flight attendants: a population-based study (Iceland). Cancer Causes and Control 12:95–101

    CAS  Google Scholar 

  66. Schernhammer ES, Laden F, Speizer FE, et al. (2001) Rotating night shifts and risk of breast cancer in women participating in the Nurses’ Health Study. J Natl Cancer Inst 93:1563–1568

    CAS  PubMed  Google Scholar 

  67. Tynes T, Hannevik M, Andersen A, Vistnes A, Haldorsen T (1996) Incidence of breast cancer in Norwegian female radio and telegraph operators. Cancer Cause Control 7:197–204

    Article  CAS  Google Scholar 

  68. Ballard T, Lagorio S, De Angelis G, Verdecchia A (2000) Cancer incidence and mortality among flight personnel: a meta-analysis. Aviat Space Environ Med 71:216–224

    CAS  PubMed  Google Scholar 

  69. Mawson AR (1998) Breast cancer in female flight attendants.Lancet 352:626

    CAS  PubMed  Google Scholar 

  70. Whelan EA (2003) Cancer incidence in airline cabin crew. Occup Environ Med 60:805–806

    CAS  PubMed  Google Scholar 

  71. Schernhammer E, Kroenke C, Laden F, Hankinson S (2005) Night work and melatonin levels in women participating in the Nurses’ Health Study II: Associate with breast cancer risk. In: 2nd Symposium of the Dana-Farber/Harvard Cancer Center Program in Breast Cancer, 2005, Boston

  72. Moller H, Mellemkjaer L, McLaughlin JK, Olsen JH (1995) Occurrence of different cancers in patients with Parkinson’s disease. BMJ 310:1500–1501

    CAS  PubMed  Google Scholar 

  73. Anton-Tay F, Diaz JL, Fernandez-Guardiola A (1971) On the effect of melatonin upon human brain. Its possible therapeutic implications. Life Sci I 10:841–850

    CAS  PubMed  Google Scholar 

  74. Fertl E, Auff E, Doppelbauer A, Waldhauser F (1991) Circadian secretion pattern of melatonin in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 3:41–47

    Article  CAS  PubMed  Google Scholar 

  75. Struppler A, Velbo-Groneberg P, Claussen M (1976) Clinic and pathophysiology of tremor In: Birkmayer W, Hornykiewicz O, (eds) Advances in Parkinsonism. Editions Roche, Basel, pp 287

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Channing Laboratory, Brigham

    Eva Schernhammer

  2. Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA

    Eva Schernhammer

  3. LBI-ACR Vienna & ACR-ITR Vienna, Austria

    Eva Schernhammer

  4. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    Honglei Chen

  5. Department of Epidemiology and Environmental Health, UCLA School of Public Health, Los Angeles, CA, USA

    Beate Ritz

  6. Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA

    Beate Ritz

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  1. Eva Schernhammer
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Correspondence to Eva Schernhammer.

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Schernhammer, E., Chen, H. & Ritz, B. Circulating Melatonin Levels: Possible Link Between Parkinson’s Disease and Cancer Risk?. Cancer Causes Control 17, 577–582 (2006). https://doi.org/10.1007/s10552-005-9002-9

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