INSPIRE grant title: Identify druggable proteins of the association of chronotype on breast cancer using Mendelian randomisation
> More about our INSPIRE Research Challenge
Emerging evidence consistently indicates that a morning chronotype may protect against breast cancer. However, modifying one’s chronotype can be challenging, as it represents an individual’s natural inclination, and people often need to adhere to daily routines that might not align with their biological chronotype in contemporary societies.
We are grateful to the World Cancer Research Fund for supporting our research, which aims to identify druggable proteins, offering alternative and viable interventions for breast cancer prevention and treatment when optimal chronotypes cannot be achieved. – Dr Shan Luo
Background
Emerging evidence consistently shows that a morning chronotype, which is the natural preference of the body to sleep and wake early, protects against breast cancer.
However, the biological mechanisms underlying the relationship remain poorly understood. This limits the ability to identify intervention targets which are particularly relevant for subpopulations where chronotypes are difficult to change (eg night shifts).
Methods
This study applied Mendelian randomisation, which is a type of analysis that looks at genetic data from different studies, to explore whether there is a connection between chronotype (ie sleep patterns) and proteins in the body, and if those proteins influence the risk of breast cancer.
Hypothesis
There are proteins in the blood that mediate the effect of chronotypes on breast cancer risk, and hence drugs that target (and reduce the levels of) these proteins can potentially be used to counteract subsequent breast cancer risk.
Aims
Identify proteins in the blood that mediate the effect of chronotype and breast cancer risk using a 2-step Mendelian randomisation study design.
Results
People who are genetically inclined to be morning types (early risers) had links to 898 different proteins. Among these, researchers found that 2 specific proteins shared a single genetic variant associated with overall breast cancer risk, with strong evidence. Further analysis suggested that these proteins explained 7% and 10% of the protective effect of being a morning person on breast cancer risk, respectively.
Conclusions
This study sheds light on how being a morning person may help reduce breast cancer risk, identifying 2 proteins that could play a key role. These findings open the door for future research into potential ways to lower breast cancer risk through targeted interventions.
Impact
To researchers’ knowledge, this study presents the first comprehensive investigation into the mechanistic pathways linking chronotype with breast cancer risk. This study highlighted a potential biological link between being a morning person and a lower risk of breast cancer, identifying 2 key proteins that may contribute to this protective effect.