Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitus
Abstract Background Recent research suggests that new-onset diabetes mellitus (NODM) often results from pancreatic cancer (PC) rather than causing it. Determining if NODM is type 2 diabetes mellitus (T2DM) or PC-related NODM (NODM-PC) aids in the early diagnosis of PC. We developed a NODM-PC risk pr...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12916-025-04048-4 |
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| author | Yu Zhou Zhuo Wu Liangtang Zeng Rufu Chen |
| author_facet | Yu Zhou Zhuo Wu Liangtang Zeng Rufu Chen |
| author_sort | Yu Zhou |
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| description | Abstract Background Recent research suggests that new-onset diabetes mellitus (NODM) often results from pancreatic cancer (PC) rather than causing it. Determining if NODM is type 2 diabetes mellitus (T2DM) or PC-related NODM (NODM-PC) aids in the early diagnosis of PC. We developed a NODM-PC risk prediction model to stratify PC risk in patients with NODM. Methods This study utilized data from the UK Biobank, including 238 NODM-PC cases and 14,825 cancer-free T2DM controls. Polygenic risk scores (PRSs) for PC and T2DM were constructed using previously reported single nucleotide polymorphisms (SNPs) separately, while the NODM-PC PRS was developed by combining SNPs from both. Non-genetic factors were selected as candidate predictors based on prior NODM-PC prediction models. We developed three Cox models to estimate the risk of PC diagnosis within 3 years in the NODM population and evaluated them by internal–external cross-validation. Results Elevated NODM-PC PRS and PC PRS scores positively correlated with NODM-PC risk, while T2DM PRS showed an inverse correlation. The NODM-PC PRS achieved the highest AUC at 0.719. Three Cox models were developed: Model 1 included age at T2DM diagnosis, smoking status, HbA1c, PC PRS, and T2DM PRS; Model 2 replaced PC and T2DM PRS with NODM-PC PRS; Model 3 included only non-genetic factors. Model 2 had the highest discrimination (Harrell’s C-index 0.823 (95% CI: 0.806–0.840)), demonstrated the best clinical utility with good calibration, and showed significant classification improvement (continuous net reclassification index: 26.89% and 31.93% for cases, 28.51% and 30.90% for controls, compared to Models 1 and 3). The positive predictive value for the top 1% predicted risk in Model 2 was 13.25%. Conclusions This NODM-PC PRS enhances NODM-PC risk prediction, efficiently identifies individuals at high risk for PC screening, and improves PC screening efficiency at the population level among NODM individuals. |
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| institution | DOAJ |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj-art-cf7b33c4aaf443dca7d64c3f381d78e42025-08-20T03:18:34ZengBMCBMC Medicine1741-70152025-04-0123111110.1186/s12916-025-04048-4Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitusYu Zhou0Zhuo Wu1Liangtang Zeng2Rufu Chen3Department of Pancreatic Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Pancreatic Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Pancreatic Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Pancreatic Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityAbstract Background Recent research suggests that new-onset diabetes mellitus (NODM) often results from pancreatic cancer (PC) rather than causing it. Determining if NODM is type 2 diabetes mellitus (T2DM) or PC-related NODM (NODM-PC) aids in the early diagnosis of PC. We developed a NODM-PC risk prediction model to stratify PC risk in patients with NODM. Methods This study utilized data from the UK Biobank, including 238 NODM-PC cases and 14,825 cancer-free T2DM controls. Polygenic risk scores (PRSs) for PC and T2DM were constructed using previously reported single nucleotide polymorphisms (SNPs) separately, while the NODM-PC PRS was developed by combining SNPs from both. Non-genetic factors were selected as candidate predictors based on prior NODM-PC prediction models. We developed three Cox models to estimate the risk of PC diagnosis within 3 years in the NODM population and evaluated them by internal–external cross-validation. Results Elevated NODM-PC PRS and PC PRS scores positively correlated with NODM-PC risk, while T2DM PRS showed an inverse correlation. The NODM-PC PRS achieved the highest AUC at 0.719. Three Cox models were developed: Model 1 included age at T2DM diagnosis, smoking status, HbA1c, PC PRS, and T2DM PRS; Model 2 replaced PC and T2DM PRS with NODM-PC PRS; Model 3 included only non-genetic factors. Model 2 had the highest discrimination (Harrell’s C-index 0.823 (95% CI: 0.806–0.840)), demonstrated the best clinical utility with good calibration, and showed significant classification improvement (continuous net reclassification index: 26.89% and 31.93% for cases, 28.51% and 30.90% for controls, compared to Models 1 and 3). The positive predictive value for the top 1% predicted risk in Model 2 was 13.25%. Conclusions This NODM-PC PRS enhances NODM-PC risk prediction, efficiently identifies individuals at high risk for PC screening, and improves PC screening efficiency at the population level among NODM individuals.https://doi.org/10.1186/s12916-025-04048-4Pancreatic cancerNew-onset diabetes mellitusPolygenic risk scoresNon-genetic factors |
| spellingShingle | Yu Zhou Zhuo Wu Liangtang Zeng Rufu Chen Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitus BMC Medicine Pancreatic cancer New-onset diabetes mellitus Polygenic risk scores Non-genetic factors |
| title | Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitus |
| title_full | Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitus |
| title_fullStr | Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitus |
| title_full_unstemmed | Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitus |
| title_short | Combining genetic and non-genetic factors to predict the risk of pancreatic cancer in patients with new-onset diabetes mellitus |
| title_sort | combining genetic and non genetic factors to predict the risk of pancreatic cancer in patients with new onset diabetes mellitus |
| topic | Pancreatic cancer New-onset diabetes mellitus Polygenic risk scores Non-genetic factors |
| url | https://doi.org/10.1186/s12916-025-04048-4 |
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