Impact of clonal hematopoiesis on cardiovascular outcomes in cancer patients of the UK Biobank
Bibliographic record
Abstract
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) have been linked to increased risks of cardiovascular disease (CVD) and mortality. CHIP and mCAs may also then contribute to CVD in cancer patients. Our objective was to investigate the prevalence of CHIP mutations and mCAs in cancer patients, their co-occurrence, and the associated CVD outcomes across different cancer types. PATIENTS AND METHODS: We carried out a case-control analysis of CHIP and mCA on the risks of CVD-related outcomes using the UK Biobank. Somatic CHIP mutations were identified from whole-exome sequencing and mCAs from genotyping data among patients diagnosed with cancers. Logistic regression and Cox proportional hazards models were used to assess the associations between CHIP mutations, mCAs, and CVD outcomes, and overall mortality. RESULTS: Overall, 2701 patients (5.5%) harbored CHIP mutations. Increasing age, current smoking, and chemotherapy exposure were associated with higher odds of CHIP mutations and mCAs. Co-occurrence of CHIP and mCAs was observed in 695 patients (25.7% of those with CHIP mutations). Loss of the Y chromosome (LOY) was inversely correlated with CHIP mutations among men [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.57-0.74, P < 0.001] whereas loss of the X chromosome (LOX) was positively correlated with CHIP mutations among women (OR 1.24, 95% CI 1.03-1.49, P = 0.03). CHIP mutations were associated with an increased risk of incident CVD [hazard ratio (HR) 1.07, 95% CI 1.02-1.13, P = 0.004] and overall mortality (HR 1.31, 95% CI 1.22-1.40, P < 0.001). Notably, there was no synergistic impact of CHIP mutations co-occurring with mCAs (LOY/LOX) on considered outcomes. CONCLUSIONS: CHIP mutations and mCAs are prevalent in cancer patients and are associated with significant increases in cardiovascular risk and mortality, with variations across cancer types. These findings underscore the importance of considering clonal hematopoiesis in the clinical management of cancer patients to mitigate cardiovascular risks.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".