Investigating causal relationships between sleep traits and risk of breast cancer: a Mendelian randomization study

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Abstract

Objective
To examine whether sleep traits have a causal effect on risk of breast cancer.
Design
Multivariable regression, one- and two-sample Mendelian randomization.
Setting
The UK Biobank prospective cohort study and the Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.
Participants
156,848 women in the multivariable regression and one-sample Mendelian randomization analysis in UK Biobank (7,784 with a breast cancer diagnosis) and 122,977 breast cancer cases and 105,974 controls from BCAC in the two-sample Mendelian randomization analysis.
Exposures
Self-reported chronotype (morning/evening preference), insomnia symptoms and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.
Main outcome measures
Breast cancer diagnosis.
Results
In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (HR 0.95, 95% CI 0.93 to 0.98 per category increase) while there was little evidence for an association with sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated 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 (HR 0.85, 95% 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 (OR 0.88, 95% CI 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (OR 1.19, 95% CI 1.02 to 1.39 per hour increase) on breast cancer (both estrogen receptor positive and negative), while there was inconsistent evidence for insomnia symptoms. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.
Conclusions
Findings revealed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.

Bibliographical metadata

Original languageEnglish
JournalB M J
Publication statusAccepted/In press - 26 Apr 2019