Abstract
The relationship between sleep traits and survival in breast cancer is uncertain and complex. There are multiple biological, psychological and treatment-related factors that could link sleep and cancer outcomes. Previous studies could be biased due to methodological limitations such as reverse causation and confounding. Here, we used two-sample mendelian randomisation (MR) to investigate the causal relationship between sleep and breast cancer mortality.
Methods
Publicly available genetic summary data from females of European ancestry from UK Biobank and 23andme and the Breast Cancer Association Consortium were used to generate instrumental variables for sleep traits (chronotype, insomnia symptoms, sleep duration, napping, daytime-sleepiness, and ease of getting up (N= 446,118-1,409,137)) and breast cancer outcomes (15 years post-diagnosis, stratified by tumour subtype and treatment (N=91,686 and Ndeaths=7,531 over a median follow-up of 8.1 years)). Sensitivity analyses were used to assess the robustness of analyses to MR assumptions.
Results
Initial results found some evidence for a per category increase in daytime-sleepiness reducing overall breast cancer mortality (HR=0.34, 95% CI=0.14, 0.80), and for insomnia symptoms reducing odds of mortality in oestrogen receptor positive breast cancers not receiving chemotherapy (HR=0.18, 95% CI=0.05, 0.68) and in patients receiving aromatase inhibitors (HR=0.23, 95% CI=0.07, 0.78). Importantly, these relationships were not robust following sensitivity analyses meaning we could not demonstrate any causal relationships.
Conclusions
This study did not provide evidence that sleep traits have a causal role in breast cancer mortality. Further work characterising disruption to normal sleep behaviours and its effects on tumour biology, treatment compliance and quality of life are needed.
| Original language | English |
|---|---|
| Article number | 357 |
| Number of pages | 25 |
| Journal | BMC Cancer |
| Volume | 25 |
| DOIs | |
| Publication status | Published - 26 Feb 2025 |
Funding
BH is funded by an Above & Beyond breast cancer legacy grant from University Hospitals Bristol NHS Foundation Trust (www.aboveandbeyond.org.uk), Cancer Research UK (C18281/A29019) and the University of Bristol Cancer Research Fund. LF is core-funded by the University of Strathclyde. OM is funded by the Business and Local Government Data Research Centre (BLG DRC) (ES/S007156/1). BH, TR, RMM, DAL and RCR are affiliated with the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol which is supported by the MRC (MC_UU_00032/01, MC_UU_00032/04, and MC_UU_00032/05) and the University of Bristol. RMM and DAL are also supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, and is a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. DAL and RMM are NIHR Senior Investigators (NF-0616-10102, NIHR202411). RMM and RCR are supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RCR is also supported by NIHR Oxford Health Biomedical Research Centre (grant number: NIHR203316). TR is supported by an NIHR Development and Skills and Enhancement Award (DSE) (NIHR 302363). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Department of Health and Social Care disclaimer: The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Keywords
- breast cancer
- sleep
- Mendelian randomisation
- epidemiology
