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Biological Clocks and Shift Work: Circadian Dysregulation and Potential Long-term Effects

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Abstract

Long-term epidemiologic studies on large numbers of night and rotating shift workers have suggested an increase in the incidence of breast and colon cancer in these populations. These studies suffer from poor definition and quantification of the work schedules of the exposed subjects. Against this background, the pathophysiology of phase shift and phase adaptation is reviewed. A phase shift as experienced in night and rotating shift work involves desynchronization at the molecular level in the circadian oscillators in the central nervous tissue and in most peripheral tissues of the body. There is a change in the coordination between oscillators with transient loss of control by the master-oscillator (the Suprachiasmatic Nucleus, SCN) in the hypothalamus. The implications of the pathophysiology of phase shift are discussed for long-term health effects and for the design of ergonomic work schedules minimizing the adverse health effects upon the worker.

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References

  1. Rutenfranz J, Knauth P, Angersbach D (1981) Shift work research issues. Biological Rhythms, Sleep and Shift Work. In: Johnson LC, Tepas TI, Colquhoun WP, Colligan MJ (eds) Advances in Sleep Research, Vol. 7. SP Medical & Scientific Books, New York, pp 165–196

  2. Pasqua IC, Moreno CRC (2004) The nutritional status and eating habits of shift workers: a chronobiologic approach. Chronobiol Int 21:949–960

    Article  CAS  PubMed  Google Scholar 

  3. Waterhouse J, Buckey P, Edwards B, Reilly T (2003) Measurement of, and some reasons for differences in eating habits between day and night workers. Chronobiol Int 20:1075–1092

    CAS  PubMed  Google Scholar 

  4. Fischer FM, Rotenberg L, de Castro Moreno CR (2004) Equity and working time. A challenge to achieve. Chronobiol Int 21:813–829

    Article  PubMed  Google Scholar 

  5. Al-Naimi S, Hampton SM, Richard P, Tzung C, Morgan LM (2004) Postprandial metabolic profiles following meals and snacks eaten during simulated night and day shift work. Chronobiol Int 21:937–947

    Article  CAS  PubMed  Google Scholar 

  6. Morgan L, Hampton S, Gibbs M, Arendt J (2003) Circadian aspects of postprandial metabolism. Chronobiol Int 20:795–808

    Article  CAS  PubMed  Google Scholar 

  7. Karlsson B, Knutsson A, Lindahl B (2001) Is there an association between shiftwork and having a metabolic syndrome X? Results from a population based study of 27,485 people. Occup Environ Med 58:747–752

    Article  CAS  PubMed  Google Scholar 

  8. Knutson A (1989) Relationships between serum triglycerides and gamma-glutamyltransferase among shift and day workers. J Intern Med 226(5):337–339

    Google Scholar 

  9. Romon M, Nuttens MC, Fievet C, etal. (1992) Increased triglyceride levels in shift workers. Am J Med 93(3):259–262

    Article  CAS  PubMed  Google Scholar 

  10. Kawachi I, Colditz GA, Stampfer MJ, etal. (1995) Prospective study of shift work and risk of coronary heart disease in women. Circulation 92(11):3178–3182

    CAS  PubMed  Google Scholar 

  11. Van Cauter E, Polonsky KS, Scheen AJ (1997) Roles of circadian rhythmicity and sleep in human glucose regulation. Endocr Rev 18:716–738

    PubMed  Google Scholar 

  12. Van Cauter E, Plat L, Copinschi G (1998) Interrelations between sleep and the somatotropic axis. Sleep 21:553–566

    PubMed  Google Scholar 

  13. Lac G, Chamoux A (2004) Biological and physiological responses to two rapid shiftwork schedules. Ergonomics 47:1339–1349

    CAS  PubMed  Google Scholar 

  14. Hennig J, Kieferdorf P, Moritz C, Huwe S, Netter P (1998) Changes in cortisol secretion during shiftwork: implications for tolerance to shiftwork. Ergonomics 41(5):610–621

    CAS  PubMed  Google Scholar 

  15. Ekstrand K, Bostrom PA, Arborelius M, Nilsson JA, Lindell SE (1996) Cardiovascular risk factors in commercial flight aircrew officers compared with those in the general population. Angiology 47(11):1089–1094

    CAS  PubMed  Google Scholar 

  16. Tenkanen L, Sjöblom T, Kalimo R, Alikoski T, Härmä M (199) Shift work occupation and coronary heart disease over 6 years of follow up in the Helsinki Heart Study. Scand J Work Environ Health 23:257–265

    Google Scholar 

  17. Härmä M (2001) Shift work and cardiovascular disease – from etiologic studies to prevention through scheduling. Scand J Env Health 27:85–86

    Google Scholar 

  18. Kristensen TS (1989) Cardiovascular diseases and the work environment. A critical review of the epidemiological literature on nonchemical factors. Scand J Work Environ Health 15:165–179

    CAS  PubMed  Google Scholar 

  19. Knutsson A (2004) Methodological aspects of shift-work research. Chronobiol Int 21:1037–1047

    PubMed  Google Scholar 

  20. Knutsson A, Hallquist J, Reuterwall C, Theorell T, Akerstedt T (1999) Shiftwork and myocardial infarction: a case-control study. Occup Environ Med 56(1):46–50

    CAS  PubMed  Google Scholar 

  21. Schernhammer ES, Laden F, Speizer FE, etal. (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 

  22. Schernhammer ES, Laden F, Speizer FE, etal. (2003) Night-Shift work and risk of colorectal cancer in the Nurses’ health study. J Natl Cancer Inst 95:825–828

    Google Scholar 

  23. Fu L, Pelicano H, Liu J, Huang P, Lee CC (2002) The circadian gene Period 2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 111:41–50

    CAS  PubMed  Google Scholar 

  24. 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 

  25. Reynolds P, Cone J, Layefsky M, Goldberg DE, Hurley S (2002) Cancer incidence in California flight attendants (United States). Cancer Causes Control 13:317–324

    PubMed  Google Scholar 

  26. Touitou Y, Haus E (eds) (1992) Biologic Rhythms in Clinical and Laboratory Medicine. Springer-Verlag, Heidelberg pp. 730

    Google Scholar 

  27. Dunlap JC (1999) Molecular bases for circadian clocks. Cell 96:271–290

    Article  CAS  PubMed  Google Scholar 

  28. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941

    Article  CAS  PubMed  Google Scholar 

  29. M Moser M Frühwirth R Penter R Winker (2006) ArticleTitleWhy life oscillates – from a topographical towards a functional chronobiology Cancer Causes Control 17 591–599

    Google Scholar 

  30. Haus E, Touitou Y (1992) Principles of clinical chronobiology. In: Touitou Y, Haus E (eds) Biologic Rhythms in Clinical and Laboratory Medicine. Springer-Verlag, Berlin, pp 6–34

    Google Scholar 

  31. Hildebrandt G, Moser M, Lehofer M (1998) Chronobiology und Chronomedicine – Biologic Rhythms Medical Consequences (in German). Hippokrates, Stuttgart

  32. Bjarnason GA, Jordan R (2002) Rhythms in human gastrointestinal mucosa and skin. Chronobiol Internat 19:129–140

    CAS  Google Scholar 

  33. Challet E, Pévet P (2003) Interaction between photic and non-photic stimuli to synchronize the master circadian clock in mammals. Front Biosci 8:246–257

    Google Scholar 

  34. Stokkan KA, Yamazaki S, Tei H, Sakaki Y, Menaker M (2001) Entrainment of the circadian clock in the liver by feeding. Science 291:490–493

    Article  CAS  PubMed  Google Scholar 

  35. Hara R, Wan K, Wakamatsu H, etal. (2001) Restricted feeding entrains liver clock without participation of the suprachiasmatic nucleus. Genes Cells 6:269–278

    CAS  PubMed  Google Scholar 

  36. Nagano M, Adachi A, Nakahama K, etal. (2003) An abrupt shift in the day/night cycle causes desynchrony in the mammalian circadian center. J Neurosci 23:6141–6151

    CAS  PubMed  Google Scholar 

  37. Sakamoto K, Ishida N (2000) Light-induced phase-shifts in the circadian expression rhythm of mammalian Period genes in the mouse heart. Eur J Neurosci 12:4003–4006

    Article  CAS  PubMed  Google Scholar 

  38. Harris W (1977) Fatigue, circadian rhythms, and truck accidents. In: Mackie R (ed) Vigilance Theory, Operational Performance, and Physiological Correlate. Plenum Press, New York, pp 1033–1046

    Google Scholar 

  39. Hildebrandt G, Rohmert W, Rutenfranz J (1974) 12 and 24 h rhythms in error frequency of locomotive drivers and the influence of tiredness. Int J Chronobiol 2:175–180

    CAS  PubMed  Google Scholar 

  40. Ribak J, Ashkenazi IE, Klepfish A, etal. (1983) Diurnal rhythmicity and air force flight accidents due to pilot error. Aviat Space Envir Med 54:1096–1099

    CAS  Google Scholar 

  41. Folkard S, Akerstedt T (2004) Trends in the risk of accidents and injuries and their implications for models of fatigue and performance Aviation. Space Environ Med 75:A161–A167

    Google Scholar 

  42. Folkard S, Lombardi DA (2004) Toward a ‘Risk Index’ to assess work schedules. Chronbiol Int 21:1063–1072

    Google Scholar 

  43. Haus E (2002) Chronobiology of the mammalian response to ionizing radiation potential applications in oncology. Chronobiol Int 19(1):77–100

    Article  PubMed  Google Scholar 

  44. Haus E, Touitou Y (1992) Principles of clinical chronobiology. In: Touitou Y, Haus E (eds) Biologic Rhythms in Clinical and Laboratory Medicine. Springer-Verlag, Heidelberg, pp 6–34

    Google Scholar 

  45. Winget CM, Soliman MRI, Holley DC, Meylor JS (1992) Chronobiology of physical performance and sports medicine. In: Touitou Y, Haus E (eds) Biologic Rhythms in Clinical and Laboratory Medicine. Springer-Verlag, Heidelberg, pp 230–242

    Google Scholar 

  46. Monk TH (1992) Chronobiology of mental performance. In: Touitou Y, Haus E (eds) Biologic Rhythms in Clinical and Laboratory Medicine. Springer-Verlag, Heidelberg, pp 208–213

    Google Scholar 

  47. Mormont MC, Waterhouse J (2002) Contribution of the rest-activity circadian rhythm to quality of life in cancer patients. Chronobiol Int 19(1):313–323

    PubMed  Google Scholar 

  48. Haus E, Nicolau GY, Lakatua D, Sackett-Lundeen L (1988) Reference values for chronopharmacology. Annu Rev Chronopharmacol 4:333–424

    CAS  Google Scholar 

  49. Haus E, Sackett-Lundeen L (2003) Variability of the circadian time structure in clinically healthy subjects. Interactions between activity patterns and time of food uptake. Shiftwork Internat Newslett 20(2):89

    Google Scholar 

  50. Waterhouse J, Nevill A, Finnegan J, et al. (2005) Further assessments of the relationship between jet lag and some of its symptoms. Chronobiol Int 22(1):121–136

    PubMed  Google Scholar 

  51. Aschoff J, Hoffman K, Pohl H, Wever R (1975) Re-entrainment of circadian rhythms after phase-shifts to the zeitgeber. Chronobiologia 2:23–78

    CAS  PubMed  Google Scholar 

  52. Klein K, Wegmann H (1974) The resynchronization of human circadian rhythms after transmeridian flights as a result of flight direction and mode of activity. In: Scheving LE (ed.) Chronobiology. Igaku-Shoin, Tokyo, pp 564–570

    Google Scholar 

  53. Klein K, Wegmann H, Athanassenas G, Hohloweck H, Kuklinski P (1976) Air operations and circadian performance rhythms. Aviation Space Environ Med 47:221–231

    CAS  Google Scholar 

  54. Beljan JR, Rosenblatt LS, Hetherington NW, etal. (1972) Human performance in aviation environment. NASA Rep NAS2-6657, part I-A

  55. Lowden A, Akerstedt T (1998) Retaining home-base sleep hours to prevent jet lag in connection with a westward flight across nine time zones. Chronobiol Int 15(4):365–376

    CAS  PubMed  Google Scholar 

  56. Reynolds P, Cone J, Layefsky M, Goldberg DE, Hurley S (2002) Cancer incidence in California flight attendants (United States). Cancer Causes Control 13(4):317–324

    Article  PubMed  Google Scholar 

  57. Rafnsson V, Tulinius H, Jonasson JG, Hrafnkelsson J (2001) Risk of breast cancer in female flight attendants: a population based study (Iceland). Cancer Causes Control 12(5):95–101

    CAS  PubMed  Google Scholar 

  58. Pukkala E, Auvinen A, Wahlberg G (1995) Incidence of cancer among Finnish airline cabin attendants, 1967–1992. BMJ 311:649–652

    CAS  PubMed  Google Scholar 

  59. Butler GC, Nicholas J, Lackland DT, Friedberg W (2000) Perspectives of those impacted: airline pilots perspective. Health Phys 79:602–607

    CAS  PubMed  Google Scholar 

  60. Friedberg W, Duke FE, Snyder L, etal. (1993) The cosmic radiation environment at air carrier flight altitudes and possible associated health risks. Radiat Prot Dosim 48:21–25

    CAS  Google Scholar 

  61. Nicholas JS, Lackland DT, Butler GC, etal. (1998) Cosmic radiation and magnetic field exposure to airline flight crews. Am J Ind Med 34:574–580

    Article  CAS  PubMed  Google Scholar 

  62. Dumont M, Benhaberou-Brun D, Paquet J (2001) Profile of 24-h light exposure and circadian phase of melatonin secretion in night workers. J Biol Rhythms 18(5):502–511

    Google Scholar 

  63. Reinberg A, Andlauer P, Bourdeleau P, Levi F, Bicakova-Rocher A (1984) Rythme circadien de la force des mains droite et gauche: désynchronisation chez certains travailleurs postés. CR Acad Sci 299:633–636

    CAS  Google Scholar 

  64. Reinberg A, Motohashi Y, Bourdeleau P, etal. (1989) Internal desynchronization of circadian rhythms and tolerance of shift work. Chronobiologia 16(1):21–34

    CAS  PubMed  Google Scholar 

  65. Reinberg A (2003) Travail posté, travail de nuit, vols transméridiens: effets et tolérance. In: Reinberg A (ed.) Chronobiologie médicale, Chronothérapeutique. Flammarion, Paris, pp 189–203

    Google Scholar 

  66. Motohashi Y (1989) Desynchronization of oral temperature and grip strength circadian rhythms in healthy subjects with irregular sleep-wake behavior. Chronobiologia 16(2):162–163

    Google Scholar 

  67. Ross JK, Arendt J, Horne J, Haston W (1995) Night-shift work during Antarctic Winter: sleep characteristics and adaptation with bright light treatment. Physiol Behav 57:1169–1174

    Article  CAS  PubMed  Google Scholar 

  68. Barnes RG, Forbes MJ, Arendt J (1998) Shift type and season affect adaptation of the 6-sulphatoxymelatonin rhythm in offshore oil rig workers. Neurosci Lett 252:179–182

    Article  CAS  PubMed  Google Scholar 

  69. Bjorvatn B, Kecklund G, Akerstedt T (1999) Bright light treatment used for adaptation to nightwork and re-adaptation back to day life. A field study at an oil platform in the North Sea. J Sleep Res 8:105–112

    Article  CAS  PubMed  Google Scholar 

  70. Gibbs M, Hamptom S, Morgan L, Arendt J (2002) Adaptation of the circadian rhythm of 6-sulphatoxy melatonin to a shift schedule of seven nights followed by seven days in offshore oil installation workers. Neurosci Lett 325:91–94

    Article  CAS  PubMed  Google Scholar 

  71. Rodrigues MC, Nogueira Pires ML, Benedito-Silva AA, Tufik S (2004) Sleep parameters among offshore workers: an initial assessment in the Campos Basin, Rio de Janeiro, Brazil. Chronobiol Int 21:889–897

    Google Scholar 

  72. Akerstedt T (2003) Shiftwork and disturbed sleep-wakefulness. Occup Med 53:89–94

    Article  Google Scholar 

  73. Folkard S, Akerstedt T, Macdonald I, Tucker P, Spencer MB (1999) Beyond the three process model of alertness: estimating phase, time on shift, and successive night effects. J Biol Rhythms 14(6):577–587

    Article  CAS  PubMed  Google Scholar 

  74. Spiegel K, Leproult R, VanCauter E (1999) Impact of sleep debt on metabolic and endocrine function. Lancet 354:1435–1439

    Article  CAS  PubMed  Google Scholar 

  75. Schedlowski M, Teves U (eds) Born in Psychoneuroimmunology: An Interdisciplinary Introduction, Plenum Publ, NY, pp. 417–442

  76. Segawa K, Nakazawa S, Tsukamoto Y, etal. (1987) Peptic ulcer is prevalent among shift workers. Digest Dis Sci 32(5):449–453

    Article  CAS  PubMed  Google Scholar 

  77. Bélanger PM, Bruguerolle B, Labrecque G (1997) Rhythms in pharmacokinetics; absorption, distribution, metabolism and excretion. In: Redfern P, Lemmer B (eds) Physiology and Pharmacology of Biological Rhythms. Spinger-Verlag, Berlin, pp 177–204

    Google Scholar 

  78. Labrecque G, Beauchamp D (2003) Rhythms and pharmacokinetics. In: Redfern PH (ed) Chronotherapeutics. Pharmaceutical Press, London, pp 75–110

    Google Scholar 

  79. Witte K, Lemmer B (2003) Rhythms and pharmacodynamics. In: Redfern PH (ed) Chronotherapeutics. Pharmaceutical Press, London, pp 111–126

    Google Scholar 

  80. Dagan Y (2002) Circadian rhythm sleep disorders (CRSD) Sleep Med Rev 6:45–54

    Article  PubMed  Google Scholar 

  81. Levi F, Zidani R, Misset JL (1997) Randomized multicenter trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet 360:681–686

    Google Scholar 

  82. Hrushesky WJ, Bjarnason GA (1993) Circadian cancer therapy. J Clin Oncol 11(7):1403–1417

    CAS  PubMed  Google Scholar 

  83. Reinberg AE (1989) Chronopharmacology of corticosteroids and ACTH. In: Lemmer B (ed) Dekker, New York, pp 137–167

  84. Lemmer B (2003) Rhythms in therapeutics of cardiovascular disease. In: Redfern PH (ed) Chronotherapeutics. Pharmaceutical Press, London, pp 193–209

    Google Scholar 

  85. Reinberg AE (2003) Chronotoxicité et chronotolerance. In: Reinberg AE (ed.) Chronobiologie médicale, Chronotherapeutique. Flammarion, Paris, pp 79–91

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  87. Arendt J (1992) The Pineal. In: Touitou Y, Haus E (eds) Biologic Rhythms in Clinical and Laboratory Medicine. Springer-Verlag, Heidelberg, pp 348–362

    Google Scholar 

  88. Travis RC, Allen DS, Fentiman IS, Key TJ (2004) Melatonin and breast cancer: a prospective study J Natl Cancer Inst 96:475–482

    CAS  PubMed  Google Scholar 

  89. 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 Lett 144:131–136

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  91. Blask DE, Dauchy RT, Sauer LA, Krause JA, Brainerd GC (2003) Growth and fatty acid metabolism of human breast cancer (MCF-7) xenografts in nude rats: impact of constant light-induced nocturnal melatonin suppression. Breast Cancer Res Treat 79:313–320

    Article  CAS  PubMed  Google Scholar 

  92. Erren TC, Reiter RJ, Pinger A, Piekavski C, Erren M (2004) The chronosense – what light tells man about biological time. Med Hypotheses 63(3):1074–1080

    PubMed  Google Scholar 

  93. Hanssen T, Heyden T, Sundberg T, Wetterberg L (1977) Effect of propanolol on serum melatonin. Lancet II 2(8032):309–310

    CAS  Google Scholar 

  94. Cowen PJ, Fraser S, Sammons R, Green AR (1983) Atenolol reduces plasma melatonin concentration in man. Br J Clin Parmacol 15:579–581

    CAS  Google Scholar 

  95. Filipski E, King VM, Xiao Mei Li, etal. (2002) Host circadian clock as control point in tumor progression. J Natl Cancer Inst 94:690–697

    PubMed  Google Scholar 

  96. Bougrine S, Mollard R, Iguazi G, Coblentz A (1995) Appropriate use of bright light promotes a durable adaptation to night shifts and accelerates readjustment during recovery after a period of night shifts. Work Stress 9:314–326

    CAS  PubMed  Google Scholar 

  97. Eastman CI, Martin SK (1999) How to use light and dark to produce circadian adaptation to night shift work. Ann Med 31:87–98

    CAS  PubMed  Google Scholar 

  98. Crowley SJ, Lee C, Tseng CY, Fogg LF, Eastman CI (2003) Combinations of bright light, scheduled dark, sunglasses, and melatonin to facilitate circadian entrainment to night shift work. J Biol Rhythms 18:513–523

    Article  PubMed  Google Scholar 

  99. Härmä M, Hakola T, Kandolin I, Sallinon I, Virkkala J, Bonnefond A (2003) A controlled intervention study of a quickly forward rotating shift system among young and elderly maintenance workers. SIN 20(2):86

    Google Scholar 

  100. Bubenik GA, Blask DE, Brown GM, etal. (1998) Prospects of the clinical utilization of melatonin. Biol Signals Recept 7:195–219

    Article  CAS  PubMed  Google Scholar 

  101. Aschoff J (1978) Features of circadian rhythms relevant for the design of shift schedules. Ergonomics 39:739–754

    Google Scholar 

  102. Hakola T, Härmä M (2001) Evaluation of a fast forward rotating shift schedule in the steel industry with a special focus on ageing and sleep. J Human Ergol 30:315–319

    CAS  Google Scholar 

  103. Orth-Gomer K (1983) Intervention on coronary risk factors by adapting a shift work schedule to biologic rhythmicity. Psychosom Med 45(5):407–415

    CAS  PubMed  Google Scholar 

  104. Prunier-Poulmaire P, Gadbois C, Derriiennic F (2003) Irregular working schedules and health: results of an epidemiological study. SIN 20(2):153

    Google Scholar 

  105. Costa G, Åkerstedt T, Nachreiner F, etal. (2004) Flexible working hours, health and well-being in Europe: some considerations from a SALTSA project. Chronobiol Int 21:831–844

    Article  PubMed  Google Scholar 

  106. Giebel O, Janssen D, Schomann C, Nachreiner F (2004) A new approach for evaluating flexible working hours. Chronobiol Int 21:1015–1024

    Article  PubMed  Google Scholar 

  107. Gärtner J (2004) Conflicts between employee preferences and ergonomic recommendations in shift scheduling: regulation based on consent is not sufficient. Rev Saúde Pública 38(Suppl):65–71

    Google Scholar 

  108. Kogi K (2004) Linking better shiftwork arrangements with safety and health management systems. Rev Saúde Pública 38(Suppl):72–79

    PubMed  Google Scholar 

  109. Buxton OM, Lee CW, L’Hermite-Balériaux M, Turek FW, Van Cauter E (2003) Exercise elicits phase shifts and acute alterations of melatonin that vary with circadian phase. Am J Physiol Regul Integr Comp Physiol 284:R714–R724

    CAS  PubMed  Google Scholar 

  110. Geoffrian M, Brun J, Chazot G, Claustrat B (1998) The physiology and pharmacology of melatonin in humans. Horm Res 49:136–141

    Google Scholar 

  111. Reinberg A, Smolensky MH, Labrecque G (1988) The hunting of the wonder pill for resetting all biological clocks. Ann Rev Chronopharmacol 4:171–208

    CAS  Google Scholar 

  112. Simpson HW, Pauson A, Cornelissen G (1989) The chronopathology of breast pre-cancer. Chronobiologia 16(4):365–372

    CAS  PubMed  Google Scholar 

  113. Wargovich MJ, Chang P, Velasco M, Sinicrope F, Eisenbrodt E, Sellin J (2004) Expression of cellular adhesion proteins and abnormal glycoproteins in human aberrant crypt foci. Appl Immunohistochem Mol Morphol 12(4):350–355

    PubMed  Google Scholar 

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Haus, E., Smolensky, M. Biological Clocks and Shift Work: Circadian Dysregulation and Potential Long-term Effects. Cancer Causes Control 17, 489–500 (2006). https://doi.org/10.1007/s10552-005-9015-4

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