368P - Causal relationships between dietary habits and prostate cancer: A two-sample Mendelian randomization study

Background

Dietary habits and prostate cancer (PCa) were linked in observational studies, while the causality remains ambiguous. We intended to explore the causal relationship between dietary factors and PCa using Mendelian randomization (MR).

Methods

Summary data from publicly available Genome-wide association studies (GWASs) were used to identify genetic variants strongly related to five dietary habits (including “never eat dairy”, “eggs”, “sugar”, “wheat”, and “I eat all of the above”) and PCa. Two-sample MR analyses were performed mainly based on the inverse-variance weighted (IVW), and MR-Egger and weighted median were applied to give consistent estimates. In addition, pathway and functional enrichment analyses were conducted to explore the potential mechanisms. Further validations were performed for the relationship between hub genes associated with genetically predicted dietary habits and PCa at a gene level.

Results

MR analyses showed that “Never eat sugar or foods/drinks containing sugar” (P_assoc = 0.012), “Never eat wheat products” (P_assoc = 0.025) and “Never eat eggs or foods containing eggs” (P_assoc = 0.048) were significantly associated with reduced risk of PCa, whereas the effect of not eating eggs was inconsistent with MR-Egger. No evidence indicated a causal relationship between “Never eat dairy products” (P_assoc = 0.398) and “Never eat eggs, dairy, wheat, sugar: I eat all of the above” (P_assoc = 0.058) and the risk of PCa. Enrichment analyses indicated that the mechanisms of “Never eat sugar or foods/drinks containing sugar” effect on PCa may be through DNA damage response and p53 signal transduction, and five genes (EP300, AURKB, H2AZ1, MAPK3, RUVBL2) were identified as hub genes, of which AURKB (P_assoc = 0.016) was causally associated with higher risk of PCa. Systemic lupus erythematosus (SLE) and ATP-dependent chromatin remodeling may mediate the effects of “Never eat wheat products” on PCa.

Conclusions

These findings support a negative association between never eating sugar or wheat products and PCa risk, indicating that interventions targeting dietary changes may mitigate the incidence of PCa.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.