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Br J Cancer. 2008 November 4; 99(9): 1502–1505.
Published online 2008 September 23. doi:  10.1038/sj.bjc.6604684
PMCID: PMC2579702

Sleep duration and the risk of breast cancer: the Ohsaki Cohort Study


In a prospective study of 23 995 Japanese women, short sleep duration was associated with higher risk of breast cancer (143 cases), compared with women who slept 7 h per day, the multivariate hazard ratio of those who slept [less-than-or-eq, slant]6 h per day was 1.62 (95% confidence interval: 1.05–2.50; P for trend=0.03).

Keywords: sleep duration, breast cancer, incidence, Japanese, prospective cohort study

Breast cancer is the commonest cancer in women, worldwide (Parkin et al, 2005). In Japan, the incidence rate age-standardised to the world population was 28.3 per 100 000 in 1991 and 39.5 in 2001 (The Research Group for Population-based Cancer Registration in Japan, 1998; Marugame et al, 2007).

Melatonin, which is secreted mainly from the pineal gland and plays a role in sleep duration, is suggested as an agent in the association between sleep duration and breast cancer (Brzezinski, 1997; Schernhammer and Schulmeister, 2004). This is because melatonin suppresses the synthesis and secretion of sex hormones by promoting the release of gonadotropin-releasing hormone (Martin and Klein, 1976; Aleandri et al, 1996). In relation to melatonin secretion, there have been several observational studies on night work or visual impairment and breast cancer (Feychting et al, 1998; Verkasalo et al, 1999; Kliukiene et al, 2001; Schernhammer et al, 2001; Megdal et al, 2005; Pukkala et al, 2006; Schwartzbaum et al, 2007). In addition, there have been three prospective cohort studies of sleep duration and the risk of breast cancer, although with inconsistent findings (Verkasalo et al, 2005; Pinheiro et al, 2006; Wu et al, 2008).

We therefore examined the association between sleep duration and the risk of breast cancer in a population of Japanese women.

Materials and methods

Details of the Ohsaki National Health Insurance (NHI) Cohort Study have been described previously (Tsuji et al, 1998; Kuriyama et al, 2006). Briefly, this prospective cohort study, started in 1994, included 28 515 women aged 40–79 years living in the 14 municipalities of Miyagi Prefecture, northeastern Japan. The response rate was 95.0% (N=27 134) for the questionnaire, including items on sleep duration and other health-related lifestyle factors. The study protocol was reviewed and approved by the ethics committee of Tohoku University School of Medicine.

After exclusion of participants who had withdrawn from the NHI before follow-up, those who had history of cancer, those who had omitted responses for sleep duration, and those who had reported sleep duration of less than 4 h or more than 12 h, 23 995 participants remained. To follow up participants for mortality and migration, we reviewed the NHI withdrawal history files for 1995–2003. Through the Miyagi Prefectural Cancer Registry, we identified 143 incident cases of breast cancer.

With regard to the sleep duration, participants answered the mean integer number of hours of sleep per day during the last year. Because of the small number who slept for less than 7 h and less than 8 h, we categorised sleep duration into four groups: [less-than-or-eq, slant]6, 7, 8, and [gt-or-equal, slanted]9 h per day. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer incidence according to sleep duration, using the Cox proportional hazards model, with adjustment for age and potential confounders. The continuous P for trend was calculated by treating sleep duration as a continuous variable, and the categorical P for trend by treating each category as a continuous variable. Interactions between the risk and all confounders were tested through the addition of cross-product terms to multivariate model.

All statistical analyses were performed using SAS statistical software, version 9.1 (SAS Institute Inc, Cary, NC, USA), and all those reported were two-sided; differences at P-values of <0.05 were accepted as significant.


Table 1 shows the baseline characteristics of participants according to sleep duration. Participants who slept 6 h or less were more likely to have a family history of cancer, to have used oral contraceptive drugs, and to be premenopausal. Participants who slept 9 h or more were older, had a smaller total caloric intake, lower educational level, were more likely to have a history of diseases, and were less likely to be employed, married, and premenopausal.

Table 1
Baseline characteristics of the participants according to sleep duration

Using women who slept 7 h as the reference group, we found an inverse association between sleep duration and breast cancer risk. The HR of women who slept 6 h or less was 1.62 (95% CI: 1.05–2.50), of those who slept 8 h was 1.14 (95% CI: 0.75–1.73), and of those who slept 9 h or more was 0.72 (95% CI: 0.36–1.43) (P for trend=0.03). This result did not change substantially when participants whose event occurred within 3 years of baseline (N=49) were excluded and stratified analysis by age and menopausal status (Table 2). In addition, we examined in detail confounding and effect modification by other covariates on the associations between sleep duration and the risk of breast cancer. No statistically significant interaction was observed between sleep duration and other confounding factors for the risk of breast cancer on a multiplicative scale (data not shown).

Table 2
Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer incidence according to sleep duration in Japanese women


This study revealed an inverse association between sleep duration and the risk of breast cancer in Japanese women, participants who slept 6 h or daily having a significantly increased risk of breast cancer.

There have been three prospective cohort studies of breast cancer in relation to sleep duration (Verkasalo et al, 2005; Pinheiro et al, 2006; Wu et al, 2008), of which the last two reported a significantly decreased risk in long sleepers and our results are consistent with these. By contrast, another study reported no such association (Pinheiro et al, 2006), possibly studied because residential nurses were studied with rotating-shift work and varying timing of sleep, so that generalising from their results may be inappropriate.

Melatonin is suggested to be involved in this relationship with sleep duration, a decrease that results in a shorter duration of nocturnal melatonin secretion (Wehr, 1991). A lower melatonin level was associated with an increased risk of breast cancer (Schernhammer and Hankinson, 2005; Schernhammer et al, 2008). Melatonin may have an inhibitory effect on gonadal function, including the synthesis and secretion of sex hormones, by promoting the release of gonadaotropin-releasing hormone (Martin and Klein, 1976; Aleandri et al, 1996); it also exerts an antiproliferative effect on breast cancer cell lines (Blask et al, 1997).

Our study had several strengths. First, we recruited participants from the general population, allowing possible generalisation of our results. Second, the Miyagi Prefectural Cancer Registry is one of the earliest and most accurate population-based cancer registries in Japan (Takano and Okuno, 1997), with only 2.7% of breast cancer cases ascertained by death certificate only (DCO) in 1998–2002 (Curado et al, 2007).

Our study also had several methodological limitations. First, we used self-reported sleep duration, and the assessment was done only once. Second, we had no information on such factors as sleep quality, the timing of sleep, the use of sleep medication, or the presence of sleeping disorders that can influence sleep duration and thereby might affect breast cancer risk. Finally, we had no information about rotating-shift work or night work, but since 23% of our participants were housewives, 19.0% farmers, and 15.7% retired, such details would have been unlikely to have changed the result substantially.

In conclusion, we have found a significant inverse association between sleep duration and breast cancer risk in Japanese women, those who slept 6 h or less having a significantly increased risk.


This study was supported by a Grant-in-Aid for Cancer Research and for the Third Term Comprehensive Ten-Year Strategy for Cancer Control (H18-3jigan-ippan-001), Ministry of Health, Labour and Welfare, Japan. Masako Kakizaki was supported in part by Global COE Program (Basic and Translational Research Center for Global Brain Science), MEXT, Japan.


  • Aleandri V, Spina V, Morini A. The pineal gland and reproduction. Hum Reprod Update. 1996;2:225–235. [PubMed]
  • Blask DE, Wilson ST, Zalatan F. Physiological melatonin inhibition of human breast cancer cell growth in vitro: evidence for a glutathione-mediated pathway. Cancer Res. 1997;57:1909–1914. [PubMed]
  • Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336:186–195. [PubMed]
  • Curado M, Edwards B, Shin H, Storm H, Ferlay J, Heanue M, Boyle P. Cancer Incidence in Five Continents 2007. In IARC Scientific Publications IARC: Lyon; Vol IX
  • Feychting M, Osterlund B, Ahlbom A. Reduced cancer incidence among the blind. Epidemiology. 1998;9:490–494. [PubMed]
  • Kliukiene J, Tynes T, Andersen A. Risk of breast cancer among Norwegian women with visual impairment. Br J Cancer. 2001;84:397–399. [PMC free article] [PubMed]
  • Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, Tsubono Y, Tsuji I. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA. 2006;296:1255–1265. [PubMed]
  • Martin JE, Klein DC. Melatonin inhibition of the neonatal pituitary response to luteinizing hormone-releasing factor. Science. 1976;191:301–302. [PubMed]
  • Marugame T, Matsuda T, Kamo K, Katanoda K, Ajiki W, Sobue T. Cancer incidence and incidence rates in Japan in 2001 based on the data from 10 population-based cancer registries. Jpn J Clin Oncol. 2007;37:884–891. [PubMed]
  • Megdal SP, Kroenke CH, Laden F, Pukkala E, Schernhammer ES. Night work and breast cancer risk: a systematic review and meta-analysis. Eur J Cancer. 2005;41:2023–2032. [PubMed]
  • Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. [PubMed]
  • Pinheiro SP, Schernhammer ES, Tworoger SS, Michels KB. A prospective study on habitual duration of sleep and incidence of breast cancer in a large cohort of women. Cancer Res. 2006;66:5521–5525. [PubMed]
  • Pukkala E, Ojamo M, Rudanko SL, Stevens RG, Verkasalo PK. Does incidence of breast cancer and prostate cancer decrease with increasing degree of visual impairment. Cancer Causes Control. 2006;17:573–576. [PubMed]
  • Schernhammer ES, Berrino F, Krogh V, Secreto G, Micheli A, Venturelli E, Sieri S, Sempos CT, Cavalleri A, Schunemann HJ, Strano S, Muti P. Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2008;100:898–905. [PMC free article] [PubMed]
  • Schernhammer ES, Hankinson SE. Urinary melatonin levels and breast cancer risk. J Natl Cancer Inst. 2005;97:1084–1087. [PubMed]
  • Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst. 2001;93:1563–1568. [PubMed]
  • Schernhammer ES, Schulmeister K. Melatonin and cancer risk: does light at night compromise physiologic cancer protection by lowering serum melatonin levels. Br J Cancer. 2004;90:941–943. [PMC free article] [PubMed]
  • Schwartzbaum J, Ahlbom A, Feychting M. Cohort study of cancer risk among male and female shift workers. Scand J Work Environ Health. 2007;33:336–343. [PubMed]
  • Takano A, Okuno Y. Japan, Miyagi Prefecture 1997. IARC: Lyon; 386–389.389In: International Agency for Research on Cancer, Parkin D, Whelan S, Ferlay J, Raymond L, Young J (eds) Vol. 17, pp
  • The Research Group for Population-based Cancer Registration in Japan Cancer incidence in Japan in 1991: estimates based on data from population-based cancer registries. The Research Group for Population-based Cancer Registration in Japan (5–3) Jpn J Clin Oncol. 1998;28:574–577. [PubMed]
  • Tsuji I, Nishino Y, Ohkubo T, Kuwahara A, Ogawa K, Watanabe Y, Tsubono Y, Bando T, Kanemura S, Izumi Y, Sasaki A, Fukao A, Nishikori M, Hisamichi S. A prospective cohort study on National Health Insurance beneficiaries in Ohsaki, Miyagi Prefecture, Japan: study design, profiles of the subjects and medical cost during the first year. J Epidemiol. 1998;8:258–263. [PubMed]
  • Verkasalo PK, Lillberg K, Stevens RG, Hublin C, Partinen M, Koskenvuo M, Kaprio J. Sleep duration and breast cancer: a prospective cohort study. Cancer Res. 2005;65:9595–9600. [PubMed]
  • Verkasalo PK, Pukkala E, Stevens RG, Ojamo M, Rudanko SL. Inverse association between breast cancer incidence and degree of visual impairment in Finland. Br J Cancer. 1999;80:1459–1460. [PMC free article] [PubMed]
  • Wehr TA. The durations of human melatonin secretion and sleep respond to changes in daylength (photoperiod) J Clin Endocrinol Metab. 1991;73:1276–1280. [PubMed]
  • Wu AH, Wang R, Koh WP, Stanczyk FC, Lee HP, Yu MC. Sleep duration, melatonin and breast cancer among Chinese women in Singapore. Carcinogenesis. 2008;29 6:1244–1248. [PMC free article] [PubMed]

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