| Title: | Predicting Pancreatic Cancer in the UK Biobank Cohort Using Polygenic Risk Scores and Diabetes Mellitus |
| Journal: | Gastroenterology |
| Published: | 21 Jan 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35065983/ |
| DOI: | https://doi.org/10.1053/j.gastro.2022.01.016 |
| URL: | https://eprints.soton.ac.uk/457214/1/PDAC_PRS_manuscript_V_3.2_marked_56_1_.pdf |
| Citations: | 33 (28 in last 2 years) as of 8 Aug 2024 |
Publication 12597
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND & AIMS: Diabetes mellitus (DM) is known to be associated with pancreatic ductal adenocarcinoma (PDAC), particularly new-onset DM (NODM). Others have developed polygenic risk scores (PRS) associated with PDAC risk. We aimed to compare the performance of these PRS in an independent cohort to determine if they can discriminate between NODM and long-standing DM patients with PDAC.</p>
METHODS: Cases (1042) and matched cancer-free controls (10,420) were drawn from the UK Biobank. Five PRS models were calculated using single nucleotide polymorphisms (SNPs) from previous studies (Nakatochi, Galeotti, Molina, Jia, and Rashkin) and a combination of these. Regression models were used to assess the association between PDAC and PRS adjusted for ancestry, smoking, DM, waist circumference, and family history of digestive cancer. Receiver operator characteristic curves and area under the curve metrics (AUC) were used to assess the performance of each PRS for classifying PDAC risk.</p>
RESULTS: The combined PRS model achieved the highest AUC (0.605), and significantly improved a clinical risk model in this cohort (AUC = 0.83; P = .0002). Individuals within the fifth quintile have a 2.74-fold increased risk of developing PDAC vs those in the first quintile (P < .001), and have a 3.05-fold increased risk of developing PDAC if they have DM vs those without DM (P < .001). The positive predictive value was 11.9% in participants without DM, 23.9% with long-standing DM, and 86.7% with NODM.</p>
CONCLUSIONS: The PDAC-related common genetic variants are more strongly associated with DM. This PRS has the potential for targeting individuals with NODM for PDAC secondary screening measures.</p>
8 Keywords
- Biological Specimen Banks
- Carcinoma, Pancreatic Ductal
- Diabetes Mellitus
- Humans
- Pancreatic Neoplasms
- Pancreatic Neoplasms
- Risk Factors
- United Kingdom
4 Authors
- Shreya Sharma
- William J Tapper
- Andrew Collins
- Zaed Z R Hamady
Enabling scientific discoveries that improve human health