Circadian disrupting exposures and breast cancer risk: a meta-analysis

  • Chunla He
  • Sonia Taj Anand
  • Mark H. Ebell
  • John E. Vena
  • Sara Wagner RobbEmail author
Review Article



Shift work, short sleep duration, employment as a flight attendant, and exposure to light at night, all potential causes of circadian disruption, have been inconsistently associated with breast cancer (BrCA) risk. The aim of this meta-analysis is to quantitatively evaluate the combined and independent effects of exposure to different sources of circadian disruption on BrCA risk in women.


Relevant studies published through January 2014 were identified by searching the PubMed database. The pooled relative risks (RRs) and corresponding 95 % confidence intervals (CIs) were estimated using fixed- or random effects models as indicated by heterogeneity tests. Generalized least squares trend test was used to assess dose–response relationships.


A total of 28 studies, 15 on shift work, 7 on short sleep duration, 3 on flight attendants, and 6 on light at night were included in the analysis. The combined analysis suggested a significantly positive association between circadian disruption and BrCA risk (RR = 1.14; 95 % CI 1.08–1.21). Separate analyses showed that the RR for BrCA was 1.19 (95 % CI 1.08–1.32) for shift work, 1.120 (95 % CI 1.119–1.121) for exposure to light at night, 1.56 (95 % CI 1.10–2.21) for employment as a flight attendant, and 0.96 (95 % CI 0.86–1.06) for short sleep duration. A dose–response analysis showed that each 10-year increment of shift work was associated with 16 % higher risk of BrCA (95 % CI 1.06–1.27) based on selected case–control studies. No significant dose–response effects of exposure to light at night and sleep deficiency were found on BrCA risk.


Our meta-analysis demonstrates that circadian disruption is associated with an increased BrCA risk in women. This association varied by specific sources of circadian disrupting exposures, and a dose–response relationship remains uncertain. Therefore, future rigorous prospective studies are needed to confirm these relationships.


Circadian disruption Breast cancer Meta-analysis 



This work was funded, in part, by the Georgia Cancer Coalition (Proposal 038505) to the Cancer Epidemiology, Prevention and Control Program (CEPC) at the Georgia Cancer Center.

Conflict of interest

The authors have declared no conflict of interests.

Supplementary material

420_2014_986_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 18 kb)


  1. Akerstedt T, Froberg JE, Friberg Y, Wetterberg L (1979) Melatonin excretion, body temperature and subjective arousal during 64 hours of sleep deprivation. Psychoneuroendocrinology 4(3):219–225CrossRefGoogle Scholar
  2. Bartlett DT (2004) Radiation protection aspects of the cosmic radiation exposure of aircraft crew. Radiat Prot Dosimetry 109(4):349–355. doi: 10.1093/rpd/nch311 CrossRefGoogle Scholar
  3. Bauer SE, Wagner SE, Burch J, Bayakly R, Vena JE (2013) A case-referent study: light at night and breast cancer risk in Georgia. Int J Health Geogr 12(1):23. doi: 10.1186/1476-072X-12-23 CrossRefGoogle Scholar
  4. Blask DE (2009) Melatonin, sleep disturbance and cancer risk. Sleep Med Rev 13(4):257–264. doi: 10.1016/j.smrv.2008.07.007 CrossRefGoogle Scholar
  5. Blask DE et al (2005) Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. Cancer Res 65(23):11174–11184. doi: 10.1158/0008-5472.CAN-05-1945 CrossRefGoogle Scholar
  6. Boivin DB, Duffy JF, Kronauer RE, Czeisler CA (1996) Dose-response relationships for resetting of human circadian clock by light. Nature 379(6565):540–542. doi: 10.1038/379540a0 CrossRefGoogle Scholar
  7. Buja A et al (2006) Cancer incidence among female flight attendants: a meta-analysis of published data. J Women Health 15(1):98–105. doi: 10.1089/jwh.2006.15.98 CrossRefGoogle Scholar
  8. Davis S, Mirick DK, Stevens RG (2001) Night shift work, light at night, and risk of breast cancer. J Natl Cancer Inst 93(20):1557–1562CrossRefGoogle Scholar
  9. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefGoogle Scholar
  10. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634CrossRefGoogle Scholar
  11. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917. doi: 10.1002/ijc.25516 CrossRefGoogle Scholar
  12. Filipski E et al (2004) Effects of chronic jet lag on tumor progression in mice. Cancer Res 64(21):7879–7885. doi: 10.1158/0008-5472.CAN-04-0674 CrossRefGoogle Scholar
  13. Filipski E et al (2005) Effects of light and food schedules on liver and tumor molecular clocks in mice. J Natl Cancer Inst 97(7):507–517. doi: 10.1093/jnci/dji083 CrossRefGoogle Scholar
  14. Fritschi L et al (2013) The association between different night shiftwork factors and breast cancer: a case-control study. Br J Cancer. doi: 10.1038/bjc.2013.544 Google Scholar
  15. Girschik J, Heyworth J, Fritschi L (2013) Self-reported sleep duration, sleep quality, and breast cancer risk in a population-based case–control study. Am J Epidemiol 177(4):316–327. doi: 10.1093/aje/kws422 CrossRefGoogle Scholar
  16. Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135(11):1301–1309Google Scholar
  17. Greenland S, Thomas DC (1982) On the need for the rare disease assumption in case-control studies. Am J Epidemiol 116(3):547–553Google Scholar
  18. Grundy A et al (2013) Increased risk of breast cancer associated with long-term shift work in Canada. Occup Environ Med. doi: 10.1136/oemed-2013-101482
  19. Haldorsen T, Reitan JB, Tveten U (2001) Cancer incidence among Norwegian airline cabin attendants. Int J Epidemiol 30(4):825–830CrossRefGoogle Scholar
  20. Hansen J (2001) Increased breast cancer risk among women who work predominantly at night. Epidemiology 12(1):74–77CrossRefGoogle Scholar
  21. Hansen J, Lassen CF (2012) Nested case-control study of night shift work and breast cancer risk among women in the Danish military. Occup Environ Med 69(8):551–556. doi: 10.1136/oemed-2011-100240 CrossRefGoogle Scholar
  22. Hansen J, Stevens RG (2012) Case-control study of shift-work and breast cancer risk in Danish nurses: impact of shift systems. Eur J Cancer 48(11):1722–1729. doi: 10.1016/j.ejca.2011.07.005 CrossRefGoogle Scholar
  23. Haus EL, Smolensky MH (2013) Shift work and cancer risk: potential mechanistic roles of circadian disruption, light at night, and sleep deprivation. Sleep Med Rev 17(4):273–284. doi: 10.1016/j.smrv.2012.08.003 CrossRefGoogle Scholar
  24. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi: 10.1136/bmj.327.7414.557 CrossRefGoogle Scholar
  25. Ijaz S et al (2013) Night-shift work and breast cancer—a systematic review and meta-analysis. Scand J Work Environ Health 39(5):431–447. doi: 10.5271/sjweh.3371 CrossRefGoogle Scholar
  26. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi: 10.3322/caac.20107 CrossRefGoogle Scholar
  27. Jia Y et al (2013) Does night work increase the risk of breast cancer? A systematic review and meta-analysis of epidemiological studies. Cancer epidemiology 37(3):197–206. doi: 10.1016/j.canep.2013.01.005 CrossRefGoogle Scholar
  28. Kakizaki M et al (2008) Sleep duration and the risk of breast cancer: the Ohsaki Cohort Study. Br J Cancer 99(9):1502–1505. doi: 10.1038/sj.bjc.6604684 CrossRefGoogle Scholar
  29. Kloog I, Portnov BA, Rennert HS, Haim A (2011) Does the modern urbanized sleeping habitat pose a breast cancer risk? Chronobiol Int 28(1):76–80. doi: 10.3109/07420528.2010.531490 CrossRefGoogle Scholar
  30. Knutsson A et al (2013) Breast cancer among shift workers: results of the WOLF longitudinal cohort study. Scand J Work Environ Health 39(2):170–177. doi: 10.5271/Sjweh.3323 CrossRefGoogle Scholar
  31. Kojo K, Pukkala E, Auvinen A (2005) Breast cancer risk among Finnish cabin attendants: a nested case-control study. Occup Environ Med 62(7):488–493. doi: 10.1136/oem.2004.014738 CrossRefGoogle Scholar
  32. Li Q, Zheng T, Holford TR, Boyle P, Zhang Y, Dai M (2010) Light at night and breast cancer risk: results from a population-based case-control study in Connecticut, USA. Cancer Causes Control 21(12):2281–2285. doi: 10.1007/s10552-010-9653-z CrossRefGoogle Scholar
  33. Lie JA, Kjuus H, Zienolddiny S, Haugen A, Stevens RG, Kjaerheim K (2011) Night work and breast cancer risk among Norwegian nurses: assessment by different exposure metrics. Am J Epidemiol 173(11):1272–1279. doi: 10.1093/aje/kwr014 CrossRefGoogle Scholar
  34. Linnersjo A, Hammar N, Dammstrom BG, Johansson M, Eliasch H (2003) Cancer incidence in airline cabin crew: experience from Sweden. Occup Environ Med 60(11):810–814CrossRefGoogle Scholar
  35. Lynge E (1996) Risk of breast cancer is also increased among Danish female airline cabin attendants. BMJ 312(7025):253CrossRefGoogle Scholar
  36. McElroy JA, Newcomb PA, Titus-Ernstoff L, Trentham-Dietz A, Hampton JM, Egan KM (2006) Duration of sleep and breast cancer risk in a large population-based case-control study. J Sleep Res 15(3):241–249. doi: 10.1111/j.1365-2869.2006.00523.x CrossRefGoogle Scholar
  37. Megdal SP, Kroenke CH, Laden F, Pukkala E, Schernhammer ES (2005) Night work and breast cancer risk: a systematic review and meta-analysis. Eur J Cancer 41(13):2023–2032. doi: 10.1016/j.ejca.2005.05.010 CrossRefGoogle Scholar
  38. Menegaux F et al (2012) Night work and breast cancer: a population-based case–control study in France (the CECILE study). Int J Cancer. doi: 10.1002/ijc.27669
  39. O’Leary ES et al (2006) Shift work, light at night, and breast cancer on Long Island, New York. Am J Epidemiol 164(4):358–366. doi: 10.1093/aje/kwj211 CrossRefGoogle Scholar
  40. Orsini NBR, Greenland S (2006) Generalized least squares for trend estimation of summarized dose-response data. Stata J 6:40–70Google Scholar
  41. Pesch B et al (2010) Night work and breast cancer—results from the German GENICA study. Scand J Work Environ Health 36(2):134–141CrossRefGoogle Scholar
  42. Pilcher JJ, Lambert BJ, Huffcutt AI (2000) Differential effects of permanent and rotating shifts on self-report sleep length: a meta-analytic review. Sleep 23(2):155–163Google Scholar
  43. Pinheiro SP, Schernhammer ES, Tworoger SS, Michels KB (2006) A prospective study on habitual duration of sleep and incidence of breast cancer in a large cohort of women. Cancer Res 66(10):5521–5525. doi: 10.1158/0008-5472.can-05-4652 CrossRefGoogle Scholar
  44. Pronk A et al (2010) Night-shift work and breast cancer risk in a cohort of Chinese women. Am J Epidemiol 171(9):953–959. doi: 10.1093/aje/kwq029 CrossRefGoogle Scholar
  45. Pukkala E et al (2012) Cancer incidence among Nordic airline cabin crew. Int J Cancer 131(12):2886–2897. doi: 10.1002/Ijc.27551 CrossRefGoogle Scholar
  46. Qin Y, Zhou Y, Zhang X, Wei X, He J (2014) Sleep duration and breast cancer risk: a meta-analysis of observational studies. Int J Cancer 134(5):1166–1173. doi: 10.1002/ijc.28452 CrossRefGoogle Scholar
  47. Rafnsson V, Sulem P, Tulinius H, Hrafnkelsson J (2003) Breast cancer risk in airline cabin attendants: a nested case-control study in Iceland. Occup Environ Med 60(11):807–809CrossRefGoogle Scholar
  48. Reynolds P, Cone J, Layefsky M, Goldberg DE, Hurley S (2002) Cancer incidence in California flight attendants (United States). Cancer Causes Control 13(4):317–324CrossRefGoogle Scholar
  49. Schernhammer ES, Hankinson SE (2009) Urinary melatonin levels and postmenopausal breast cancer risk in the Nurses’ Health Study cohort. Cancer Epidemiol Biomark Prevent 18(1):74–79. doi: 10.1158/1055-9965.EPI-08-0637 CrossRefGoogle Scholar
  50. Schernhammer ES et al (2001) Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study. J Natl Cancer Inst 93(20):1563–1568CrossRefGoogle Scholar
  51. Schernhammer ES, Kroenke CH, Laden F, Hankinson SE (2006) Night work and risk of breast cancer. Epidemiology 17(1):108–111CrossRefGoogle Scholar
  52. Schernhammer ES et al (2008) Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 100(12):898–905. doi: 10.1093/jnci/djn171 CrossRefGoogle Scholar
  53. Schernhammer ES et al (2010) Urinary 6-Sulphatoxymelatonin levels and risk of breast cancer in premenopausal women: the ORDET cohort. Cancer Epidemiol Biomark Prevent 19(3):729–737. doi: 10.1158/1055-9965.EPI-09-1229 CrossRefGoogle Scholar
  54. Schwartzbaum J, Ahlbom A, Feychting M (2007) Cohort study of cancer risk among male and female shift workers. Scand J Work Environ Health 33(5):336–343CrossRefGoogle Scholar
  55. Stroup DF et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012CrossRefGoogle Scholar
  56. Verkasalo PK et al (2005) Sleep duration and breast cancer: a prospective cohort study. Cancer Res 65(20):9595–9600. doi: 10.1158/0008-5472.can-05-2138 CrossRefGoogle Scholar
  57. Wang F et al (2013) A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer. Ann Oncol 24(11):2724–2732. doi: 10.1093/annonc/mdt283 CrossRefGoogle Scholar
  58. Wartenberg D, Stapleton CP (1998) Risk of breast cancer is also increased among retired US female airline cabin attendants. BMJ 316(7):1902CrossRefGoogle Scholar
  59. Wehr TA, Aeschbach D, Duncan WC Jr (2001) Evidence for a biological dawn and dusk in the human circadian timing system. J Physiol 535(Pt 3):937–951CrossRefGoogle Scholar
  60. Wells GA et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
  61. Wu AH, Wang R, Koh WP, Stanczyk FZ, Lee HP, Yu MC (2008) Sleep duration, melatonin and breast cancer among Chinese women in Singapore. Carcinogenesis 29(6):1244–1248. doi: 10.1093/carcin/bgn100 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Chunla He
    • 1
  • Sonia Taj Anand
    • 1
  • Mark H. Ebell
    • 1
  • John E. Vena
    • 2
  • Sara Wagner Robb
    • 1
    Email author
  1. 1.Department of Epidemiology and Biostatistics, College of Public HealthUniversity of GeorgiaAthensUSA
  2. 2.Department of Public Health Sciences, College of MedicineMedical University of South CarolinaCharlestonUSA

Personalised recommendations