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BMJ. 2019 Jun 26;365:l2327. doi: 10.1136/bmj.l2327.

Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.

Author information

1
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK Rebecca.richmond@bristol.ac.uk.
2
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
3
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
4
Centre for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
5
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
6
Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
7
K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
8
Clinic of Thoracic and Occupational Medicine, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
9
Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
10
Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, Manchester, UK.
11
International Agency for Research on Cancer, Lyon, France.
12
School of Experimental Psychology, University of Bristol, Bristol, UK.
13
National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.
14
Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
15
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

OBJECTIVE:

To examine whether sleep traits have a causal effect on risk of breast cancer.

DESIGN:

Mendelian randomisation study.

SETTING:

UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.

PARTICIPANTS:

156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis.

EXPOSURES:

Self reported chronotype (morning or evening preference), insomnia symptoms, and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.

MAIN OUTCOME MEASURE:

Breast cancer diagnosis.

RESULTS:

In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (hazard ratio 0.95, 95% confidence interval 0.93 to 0.98 per category increase), whereas there was little evidence for an association between sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated with sleep duration, and 57 SNPs associated with insomnia symptoms, one sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (0.85, 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two sample MR using data from BCAC supported findings for a protective effect of morning preference (inverse variance weighted odds ratio 0.88, 95% confidence interval 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (1.19, 1.02 to 1.39 per hour increase) on breast cancer risk (both oestrogen receptor positive and oestrogen receptor negative), whereas evidence for insomnia symptoms was inconsistent. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.

CONCLUSIONS:

Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.

PMID:
31243001
PMCID:
PMC6592406
DOI:
10.1136/bmj.l2327
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf. MKR reports receiving research funding from Novo Nordisk, consultancy fees from Novo Nordisk and Roche Diabetes Care, and modest owning of shares in GlaxoSmithKline, outside the submitted work. DAL reports receiving research support from Medtronic and Roche Diagnostics for research outside the submitted work. All other authors declare no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

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