https://orcid.org/0000-0001-7825-5087
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Abstract
Background
Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways.
Methods
We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed.
Results
The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly.
Conclusion
In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.
The current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.
The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiota
Our results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.
Highlights
Ethics Approval and Consent to Participate
All studies have existing ethical permissions from their respective institutional review boards and include participant written informed consent and rigorous quality control. Because all analyses herein are based on publicly available summary data, no ethical approval from an institutional review board was required for the current study.
Authors’ Contributions
Y.T.C, E.Y.W.Y: conceived and designed the study; E.Y.W.Y: supervision; Y.T.C, Q.Y.T: conducted data analyses and interpretation and drafted the manuscript; Y.T.C, Q.Y.T: data curation; Y.X.Z, S.Z.W, A.W, W.C.L, M.P.Z: critical revision of the manuscript. All authors read and approved the final manuscript.
Disclosure Statement
No potential conflicts of interest relevant to this article were reported.
Data Availability Statement
This work has been conducted using multiple publicly available resources. The data that support the current study and findings could be accessed according to each resource’s guideline. Further information is available from the corresponding author upon request. Analysis code is available via: https://github.com/TeamEYu/MR-of-bc. Supplementary materials with detailed data and additional information are available online. To access these files, please visit https://doi.org/10.6084/m9.figshare.24745152.