Abstract
There is increasing interest in the possibility that disruption of normal circadian rhythm may increase the risk of developing cancer. Persons who engage in nightshift work may exhibit altered nighttime melatonin levels and reproductive hormone profiles that could increase the risk of hormone-related diseases, including breast cancer. Epidemiologic studies are now beginning to emerge suggesting that women who work at night, and who experience sleep deprivation, circadian disruption, and exposure to light-at-night are at an increased risk of breast cancer, and possibly colorectal cancer as well. Several studies have been conducted in Seattle recently to investigate the effects of factors that can disrupt circadian rhythm and alter normal nocturnal production of melatonin and reproductive hormones of relevance to breast cancer etiology. Studies completed to date have found: (1) an increased risk of breast cancer associated with indicators of exposure to light-at-night and night shift work; and (2) decreased nocturnal urinary levels of 6-sulphatoxymelatonin associated with exposure to 60-Hz magnetic fields in the bedroom the same night, and a number of other factors including hours of daylight, season, alcohol consumption and body mass index. Recently completed is an experimental crossover study designed to investigate whether exposure to a 60-Hz magnetic field under controlled conditions in the home sleeping environment is associated with a decrease in nocturnal urinary concentration of 6-sulphatoxymelatonin, and an increase in the urinary concentration of luteinizing hormone, follicle stimulating hormone, and estradiol in a sample of healthy women of reproductive age. Presently underway is a study to determine whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased urinary concentrations of the reproductive hormones listed above in a sample of healthy women of reproductive age, and to elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified. A proposal is under review to extend these studies to a sample of healthy men to investigate whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased concentrations of urinary cortisol and cortisone, urinary levels of a number of androgen metabolites, and serum concentrations of a number of reproductive hormones. Secondarily, the proposed study will elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified, as well as investigate whether polymorphisms of the genes thought to regulate the human circadian clock are associated with the ability to adapt to night shift work. It is anticipated that collectively these studies will enhance our understanding of the role of circadian disruption in the etiology of cancer.
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References
Angersbach D, Knauth P, Loskant H, etal. (1980) A retrospective cohort study comparing complaints and diseases in day and shift workers. Intern Arch Occup Environ Health 45:127–140
Colligan MJ, Frock IJ, Tasto D (1980) Shift work – the incidence of medication use and physical complaints as a function of shift. Occupational and Health Symposia – 1978. Washington, DC: US Dept of Health, Education and Welfare. (NIOSH Publication 80–105)
Minors DS, Scott AR, Waterhouse JM (1986) Circadian arrhythmia: shiftwork, travel and health. J Soc Occup Med 36:39–44
Knutsson A, Hallquist J, Reuterwall C, etal. (1999) Shift work and myocardial infarction: a case–control study. Occup Environ Med 56:46–50
Steenland K, Fine L (1996) Shift work, shift change, and risk of death from heart disease at work. Am J Ind Med 29:278–281
Tuchsen F (1993) Working hours and ischaemic heart disease in Danish men: a 4-year cohort study of hospitalization. Int J Epidemiol 22:215–221
Knutsson A, Akerstedt T, Jonsson BG, etal. (1986) Increased risk of ischaemic heart disease in shift workers. Lancet 2:89–92
Kawachi I, Colditz GA, Stampfer MJ, etal. (1995) Prospective study of shift work and risk of coronary heart disease in women. Circulation 92:3178–3182
Alfredsson L, Karasek R, Theorell T (1982) Myocardial infarction risk and psychosocial work environment: an analysis of the male Swedish working force. Soc Sci Med 16:463–467
Tenkanen L, Sjoblom T, Kalimo R, etal. (1997) 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
Mammalle N, Laumon E, Lazar P (1984) Prematurity and occupational activity during pregnancy. Am J Epidemiol 119:309
McDonald AD, McDonald JC, Armstrong B, etal. (1988) Prematurity and work in pregnancy. Br J Ind Med 45:56–62
Nurminen T (1989) Shift work, fetal development and course of pregnancy. Scand J Work Environ Health 15:395–403
Arendt J, Deacon S (1997) Treatment of circadian rhythm disorders–melatonin. Chronobiol Int 14:185–204
Axelsson G, Rylander R, Molin I (1989) Outcome of pregnancy in relation to irregular and inconvenient work schedules. Br J Ind Med 46:393–398
Xu X, Ding M, Li B, Christiani DC (1994) Association of rotating shiftwork with preterm births and low birth weight among never smoking women textile workers in China. Occup Environ Med 51:470–474
McDonald AD, McDonald JC, Armstrong B, et al. (1988) Fetal death and work in pregnancy. Br J Ind Med 45:148–157
Axelsson G, Ahlborg G Jr, Bodin L (1996) Shift work, nitrous oxide exposure, and spontaneous abortion among Swedish midwives. Occup Environ Med 53:374–378
Axelsson G, Lutz C, Rylander R (1984) Exposure to solvents and outcome of pregnancy in university laboratory employees. Br J Ind Med 41:305–312
Hemminki K, Kyyronen P, Lindbohm ML (1985) Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome. J Epidemiol Community Health 39:141–147
Uehata T, Sasakawa N (1982) The fatigue and maternity disturbances of night workwomen. J Hum Ergol (Tokyo) 11:465–474
Ahlborg G Jr, Axelsson G, Bodin L (1996) Shift work, nitrous oxide exposure and subfertility among Swedish midwives. Int J Epidemiol 25:783–790
Bisanti L, Olsen J, Basso O, etal. (1996) Shift work and subfecundity: a European multicenter study. J Occup Environ Med 38:352–358
Hansen J (2001) Increased breast cancer risk among women who work predominantly at night. Epidemiology 12:74–77
Davis S, Mirick DK, Stevens RG (2001) Night shift work, light at night, and the risk of breast cancer. J Natl Cancer Inst 93:1557–1562
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
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
Pukkala E, Auvinen H, Wahlberg G (1995) Incidence of cancer among Finnish airline cabin attendants. BMJ 311:649–652
Rafnsson V, Tulinius H, Jonasson JG, etal. (2001) Risk of breast cancer in female flight attendants: a population-based study (Iceland). Cancer Causes Control 12:95–101
Tynes T, Hannevik M, Andersen A, etal. (1996) Incidence of breast cancer in Norwegian female radio and telegraph operators. Cancer Causes Control 7:197–204
Band PR, Spinelli JJ, Ng VTY, etal. (1990) Mortality and cancer incidence in a cohort of commercial airline pilots. Aviat Space Environ Med 61:299–302
Irvine D, Davies DM (1992) The mortality of British Airways pilots 1966–89:a proportional mortality study. Aviat Space Environ Med 63:276–279
Band PR, Le ND, Fang R, etal. (1996) Cohort study of Air Canada pilots: mortality, cancer incidence, and leukemia risk. Am J Epidemiol 143:137–143
Krstev S, Baris D, Stewart PA, etal. (1998) Risk for prostate cancer by occupation and industry: a 24-state death certificate study. Am J Ind Med 34:413–420
Irvine D, Davies DM (1999) British Airways flightdeck mortality study, 1950–92. Aviat Space Environ Med 70:548–555
Rfnassan V, Hrafnkelsson J, Tulinius H (2000) Incidence of cancer among commercial airline pilots. Occup Environ Med 57:175–179
Pukkala E, Aspholm R, Auvinen A, etal. (2002) Incidence of cancer among Nordic airline pilots over five decades: occupational cohort study. BMJ 325:567–569
Pukkala E, Aspholm R, Auvinen A, etal. (2003) Cancer incidence among 10,211 airline pilots: a Nordic study. Aviat Space Environ Med 74:699–706
Krstev S, Baris D, Stewart P, etal. (1998) Occupational risk factors and prostate cancer in U.S. blacks and whites. Am J Ind Med 34:421–430
Demers PA, Checkoway H, Vaughan TL, etal. (1994) Cancer incidence among firefighters in Seattle and Tacoma, Washington (United States). Cancer Causes Control 5:129–135
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
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
Cos S, Fernandez R, Guezmes A, etal. (1998) Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells.Cancer Res 58:4383–4390
Cos S, Mediavilla MD, Fernandez R, etal. (2002) Does melatonin induce apoptosis in MCF-7 human breast cancer cells in vitro? J Pineal Res 32:90–96
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
Siu SW, Lau KW, Tam PC, etal. (2002) Melatonin and prostate cancer cell proliferation: interplay with castration, epidermal growth factor, and androgen sensitivity. Prostate 52:106–122
Rimler A, Lupwitz Z, Zisapel N (2002) Differential regulation by melatonin of cell growth and androgen receptor binding to the androgen response element in prostate cancer cells. Neuroendocrinol Lett 23:45–49
Marelli MM, Limonta P, Maggi R, etal. (2000) Growth-inhibitory activity of melatonin on human androgen-independent DU 145 prostate cancer cells. Prostate 45:238–244
Xi SC, Tam PC, Brown GM, etal. (2000) Potential involvement of mt1 receptor and attenuated sex steroid-induced calcium influx in the direct anti-proliferative action of melatonin on androgen-responsive LNCaP human prostate cancer cells. J Pineal Res 29:172–183
Moretti RM, Marelli MM, Maggi R, etal. (2000) Anti-proliferative action of melatonin on human prostate cancer LNCaP cells. Oncol Rep 7:347–351
Philo R, Berkowitz AS (1988) Inhibition of dunning tumor growth by melatonin. J Urol 139:1099–1102
Sze SF, Ng TB, Liu WK (1993) Anti-proliferative effect of pineal indoles on cultured tumor cell lines. J Pineal Res 14:27–33
Ying SW, Niles LP, Crocker C (1993) Human malignant melanoma cells express high-affinity receptors for melatonin: anti-proliferative effects of melatonin and 6-chloromelatonin. Eur J Pharmacol 246:89–96
Petranka J, Baldwin WS, Bierman J, etal. (1999) The oncostatic action of melatonin in an ovarian carcinoma cell line. J Pineal Res 26:129–136
Shiu SY, Li L, Xu JN, etal. (1999) Melatonin-induced inhibition of proliferation and G1/S cell cycle transition delay of human choriocarcinoma JAr cells: possible involvement of MT2 (MEL1B) receptor. J Pineal Res 27:183–192
Kanishi Y, Kobayashi Y, Noda S, etal. (2000) Differential growth inhibitory effect of melatonin on two endometrial cancer cell lines. J Pineal Res 28:227–233
Tamarkin L, Cohen M, Roselle D, etal. (1981) Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat. Cancer Res 41:4432–4436
Musatov SA, Anisimov VN, Andre V, etal. (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
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
Anisimov VN, Kvetnoy IM, Chumakova NK, etal. (1999) Melatonin and colon carcinogenesis. Exp Toxicol Pathol 51:47–52
Cini G, Coronnello M, Mini E, etal. (1988) Melatonin’s growth-inhibitory effect on hepatoma AH 130 in the rat. Cancer Lett 125:51–59
Mocchegiani E, Perissin L, Santarelli L, etal. (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
Subramanian A, Kothari L (1991) Melatonin, a suppressor of spontaneous murine mammary tumors. J Pineal Res 10(3):136–140
Jochle W (1964) Trends in photophysiologic concepts. Ann N Y Acad Sci 117:88–104
Shah PN, Mhatre MC, Kothari LS (1984) Effect of melatonin on mammary carcinogenesis in intact and pinealectomized rats in varying photoperiods. Cancer Res 44:3403–3407
Blask DE, Sauer LA, Dauchy R, etal. (1999) New actions of melatonin on tumor metabolism and growth. Biol Signals Recept 8:49–55
Blask DE, Dauchy RT, Sauer LA, etal. (2002) Light during darkness, melatonin suppression and cancer progression. Neuroendocrinol Lett 23:52–56
Dauchy RT, Sauer LA, Blask DE, etal. (1997) Light contamination during the dark phase in “photoperiodically controlled” animal rooms: effect on tumor growth and metabolism in rats. Lab Anim Sci 47:511–518
Dauchy RT, Blask DE, Sauer LA, etal. (1999) Dim light during darkness stimulates tumor progression by enhancing tumor fatty acid uptake and metabolism. Cancer Lett 144:131–136
Hahn RA (1991) Profound bilateral blindness and the incidence of breast cancer. Epidemiology 2:208–210
Feychting M, Osterlund B, Ahlbom A (1998) Reduced cancer incidence among the blind. Epidemiology 9:490–494
Pukkala E, Verkasalo PK, Ojamo M, etal. (1999) Visual impairment and cancer: a population-based cohort study in Finland. Cancer Causes Control 10:13–20
Verkasalo PK, Pukkala E, Stevens RG, etal. (1999) Inverse association between breast cancer incidence and degree of visual impairment in Finland. Br J Cancer 80:1459–1460
Kliukiene J, Tynes T, Andersen A (2001) Risk of breast cancer among Norwegian women with visual impairment. Br J Cancer 84:397–399
Reppert SM, Weaver DR (2001) Molecular analysis of mammalian circadian rhythms. Annu Rev Physiol 63:647–676
Katzenberg D, Young T, Finn L, etal. (1998) A CLOCK polymorphism associated with human diurnal preference. Sleep 21:569–576
Johansson C, Willeit M, Smedh C, etal. (2003) Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference. Neuropsychopharmacology 28(4):734–739
Archer SN, Robilliard DL, Skene DJ, etal. (2003) A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep 26:413–415
Ebisawa T, Uchiyama M, Kajimura N, etal. (2001) Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome. EMBO Rep 2:342–346
Parry BL, Newton RP (2001) Chronobiological basis of female-specific mood disorders. Neuropsychopharmacology 25:S102–S108
Zhu Y, Brown HN, Zhang Y, etal. (2005) Period3 structural variation: a circadian biomarker associated with breast cancer in young women. Cancer Epidemiol Biomarkers Prev 14:268–270
Fu L, Pelicano H, Liu J, etal. (2002) The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 111:41–50
Davis S, Kaune WT, Mirick D, Chen C, Stevens RG. (2001) Residential Magnetic Fields, Light-at-Night, and Nocturnal Urinary 6-sulphatoxymelatonin in Women. Am J Epidemiol 154:591–600
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Davis, S., Mirick, D.K. Circadian Disruption, Shift Work and the Risk of Cancer: A Summary of the Evidence and Studies in Seattle. Cancer Causes Control 17, 539–545 (2006). https://doi.org/10.1007/s10552-005-9010-9
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DOI: https://doi.org/10.1007/s10552-005-9010-9