Estimating the carcinogenesis timelines in early-onset versus late-onset cancers and changes across birth cohorts
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View abstract on PubMed
Summary
This summary is machine-generated.Key mutations for breast, colorectal, and thyroid cancers initiate early in life. Cancer progression is faster in early-onset cases and more recent birth cohorts, informing cancer prevention strategies.
Area Of Science
- Oncology
- Mathematical Biology
- Cancer Research
Background
- Understanding the timing of mutational events is crucial for cancer prevention and detection, especially for early-onset cancers.
- Intermediate mutational events in cancer development are difficult to observe directly in humans.
Purpose Of The Study
- To estimate the timing of intermediate mutational events for breast, colorectal, and thyroid cancers using a tumor kinetic model.
- To analyze differences in carcinogenesis timelines between early- and late-onset cases and across birth cohorts.
Main Methods
- Developed and extended a tumor kinetic model using ordinary differential equations to describe carcinogenesis stages.
- Utilized long-term cancer registries data, incidence, and tumor size data to fit model parameters.
- Applied a convolution-based method to derive probability distributions and compute expected ages for mutational transitions.
Main Results
- Initial mutations for breast, colorectal, and thyroid cancers are estimated to occur early in life.
- Malignant transformation for breast and colorectal cancers is faster in early-onset cases (late 30s) compared to late-onset cases (late 40s-early 50s).
- Thyroid cancer shows similar early malignant transformation timelines (late 20s) for both early- and late-onset cases.
- More recent birth cohorts exhibit a shift toward earlier malignant transformation due to faster progression of later-stage transitions.
Conclusions
- The study provides the first direct, cohort-specific estimates of key mutational transition timings over the life course.
- Findings indicate diverging carcinogenesis timelines between early- and late-onset cancers and temporal shifts across birth cohorts.
- The results can inform early-onset cancer etiologic studies and the development of targeted intervention strategies.
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