| Title: | Abdominal obesity is a more important causal risk factor for pancreatic cancer than overall obesity |
| Journal: | European Journal of Human Genetics |
| Published: | 10 May 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37161092/ |
| DOI: | https://doi.org/10.1038/s41431-023-01301-3 |
| URL: | https://www.nature.com/articles/s41431-023-01301-3.pdf |
Publication 11431
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Abstract
Obesity and type 2 diabetes (T2D) are associated with increased risk of pancreatic cancer. Here we assessed the relationship between pancreatic cancer and two distinct measures of obesity, namely total adiposity, using BMI, versus abdominal adiposity, using BMI adjusted waist-to-hip ratio (WHRadjBMI) by utilising polygenic scores (PGS) and Mendelian randomisation (MR) analyses. We constructed z-score weighted PGS for BMI and WHRadjBMI using publicly available data and tested for their association with pancreatic cancer defined in UK biobank (UKBB). Using publicly available summary statistics, we then performed bi-directional MR analyses between the two obesity traits and pancreatic cancer. PGSBMI was significantly (multiple testing-corrected) associated with pancreatic cancer (OR[95%CI] = 1.0804[1.025-1.14], P = 0.0037). The significance of association declined after T2D adjustment (OR[95%CI] = 1.073[1.018-1.13], P = 0.00904). PGSWHRadjBMI association with pancreatic cancer was at the margin of statistical significance (OR[95%CI] = 1.047[0.99-1.104], P = 0.086). T2D adjustment effectively lost any suggestive association of PGSWHRadjBMI with pancreatic cancer (OR[95%CI] = 1.039[0.99-1.097], P = 0.14). MR analyses showed a nominally significant causal effect of WHRadjBMI on pancreatic cancer (OR[95%CI] = 1.00095[1.00011-1.0018], P = 0.027) but not for BMI on pancreatic cancer. Overall, we show that abdominal adiposity measured using WHRadjBMI, may be a more important causal risk factor for pancreatic cancer compared to total adiposity, with T2D being a potential driver of this relationship.</p>
10 Authors
- Jared G. Maina
- Vincent Pascat
- Liudmila Zudina
- Anna Ulrich
- Igor Pupko
- Amélie Bonnefond
- Zhanna Balkhiyarova
- Marika Kaakinen
- Philippe Froguel
- Inga Prokopenko
1 Application
| Application ID | Title |
|---|---|
| 37685 | Dissecting predisposition and risk prediction for cardiometabolic disease, cancer and their co-occurrence: a trans-ethnic study |
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