| Title: | Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study |
| Journal: | Cell Reports Medicine |
| Published: | 26 Jan 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38280379/ |
| DOI: | https://doi.org/10.1016/j.xcrm.2023.101391 |
| URL: | http://www.cell.com/article/S2666379123006201/pdf |
Publication 8864
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Abstract
Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N = 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p < 5 × 10-8) from a genome-wide association study in the UK Biobank (N = 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidence for a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.</p>
11 Authors
- Hajime Yamazaki
- Samantha A. Streicher
- Lang Wu
- Shunichi Fukuhara
- Róbert Wagner
- Martin Heni
- Steven R. Grossman
- Heinz-Josef Lenz
- Veronica Wendy Setiawan
- Loïc Le Marchand
- Brian Z. Huang
1 Application
| Application ID | Title |
|---|---|
| 93426 | Causes and consequences of fat distribution patterns in the liver, pancreas, skeletal muscle, heart, kidney, and visceral bed |
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