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Modeling Early-Onset Cancer Kinetics Reveals Changes in Underlying Risk and the Impact of Population Screening
Navid Mohammad Mirzaei1, Chin Hur1,2,3, Mary Beth Terry1,3,4
1Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Cancer Research
|August 29, 2025
Summary
Increases in early-onset cancer may be due to true risk increases, not just earlier detection. A new model incorporating tumor size suggests accelerated cancer development and higher risks for breast, colorectal, and thyroid cancers in recent birth cohorts.
Area of Science:
- Oncology
- Epidemiology
- Biostatistics
Background:
- Rising early-onset cancer incidence (diagnosed <50 years) prompts investigation into apparent vs. true risk increases.
- Traditional cancer models often assume detection at first malignant cell, not accounting for diagnostic improvements or tumor size.
Purpose of the Study:
- To develop and validate a novel Multi-Stage Clonal Expansion (MSCE) model incorporating tumor-size-at-diagnosis to differentiate apparent from true increases in early-onset cancer incidence.
- To assess changes in cancer risk and detection dynamics across birth cohorts (1950-1984) for colorectal, breast, and thyroid cancers.
Main Methods:
- Introduced an enhanced MSCE framework explicitly integrating tumor-size-at-diagnosis to account for improved cancer detection over time.
- Applied the refined model to analyze incidence data for colorectal, breast, and thyroid cancers in three birth cohorts.
- Evaluated the model's performance in distinguishing true risk increases from detection artifacts and assessed screening impacts.
Main Results:
- The enhanced MSCE model demonstrated structural identifiability and superior parameter estimation compared to the classic model.
- Analyses revealed accelerated carcinogenic events and shorter mean sojourn times in more recent birth cohorts for the studied cancers.
- Model application supported true increases in early-onset cancer risk for breast, colorectal, and thyroid cancers in recent years.
Conclusions:
- Incorporating tumor-size-at-diagnosis is crucial for accurate cancer modeling, enabling differentiation between detection improvements and true risk changes.
- Findings support a genuine increase in early-onset cancer risk, particularly for breast, colorectal, and thyroid cancers, in recent birth cohorts.
- The refined modeling approach offers valuable insights into cancer etiology and the impact of screening interventions.
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