| Title: | Elevated circulating glycine levels are associated with reduced pancreatic cancer risk: A prospective cohort study based on the UK biobank |
| Journal: | Pancreatology |
| Published: | 15 Dec 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41421942/ |
| DOI: | https://doi.org/10.1016/j.pan.2025.12.015 |
Publication 17142
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Abstract
BACKGROUND: Identifying biomarkers associated with pancreatic cancer (PC) development could facilitate early intervention and improve outcomes.</p>
METHODS: This study enrolled 206,363 participants, with 854 incident cases of PC were identified during follow-up. 168 metabolic biomarkers were measured by nuclear magnetic resonance spectroscopy, and the polygenic risk score (PRS) for PC constructed by 44 single nucleotide polymorphisms was calculated. Multivariate Cox regression analysis and multiple hypothesis testing were employed to evaluate the association between metabolites and PC risk. Stratified analyses and interaction tests were conducted to explore the effects of metabolites under different genetic backgrounds and lifestyle factors.</p>
RESULTS: After correction for multiple hypothesis testing, only plasma glycine levels showed a significant inverse correlation with PC risk (FDR-corrected P-value <0.05). High glycine levels were associated with a 21.4 % reduction in PC risk compared to low levels (HR: 0.786, 95 % CI: 0.657-0.940). PRS was positively associated with PC risk, with high PRS participants showing a 2.871-fold increased risk (95 % CI: 2.382-3.460). Glycine's protective effects were more pronounced in low PRS participants and never smokers. High glycine and low PRS participants demonstrated a 72.3 % reduction in PC risk compared to low glycine and high PRS participants (HR: 0.277, 95 % CI: 0.197-0.389). Notably, even among participants with the highest PRS, baseline plasma glycine levels were still significantly inversely associated with future PC risk.</p>
CONCLUSION: Higher circulating glycine levels are associated with a reduced risk of PC, even in individuals with the highest genetic susceptibility. These findings suggest that higher circulating glycine levels may hold potential for PC prevention strategies, warranting further experimental validation of glycine supplementation in prospective trials.</p>
16 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Biomarkers, Tumor
- Cohort Studies
- Female
- Glycine
- Humans
- Male
- Middle Aged
- Pancreatic Neoplasms
- Polymorphism, Single Nucleotide
- Prospective Studies
- Risk Factors
- UK Biobank
- United Kingdom
7 Authors
- Shuai Xiang
- Yunlong Li
- Yuxin Wang
- Hongxu Nie
- Chengfeng Wang
- Xu Che
- Yongxing Du
1 Application
| Application ID | Title |
|---|---|
| 534846 | Study on the Correlation Between Multi-System Metabolic Dysregulation Syndrome and Digestive System Cancers in Populations with Different Genetic Risk Profiles |
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