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Predicting colorectal cancer risk from adenoma detection via a two-type branching process model

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  • Brian M Lang
  • Jack Kuipers
  • Benjamin Misselwitz
  • Niko Beerenwinkel

Abstract

Despite advances in the modeling and understanding of colorectal cancer development, the dynamics of the progression from benign adenomatous polyp to colorectal carcinoma are still not fully resolved. To take advantage of adenoma size and prevalence data in the National Endoscopic Database of the Clinical Outcomes Research Initiative (CORI) as well as colorectal cancer incidence and size data from the Surveillance Epidemiology and End Results (SEER) database, we construct a two-type branching process model with compartments representing adenoma and carcinoma cells. To perform parameter inference we present a new large-size approximation to the size distribution of the cancer compartment and validate our approach on simulated data. By fitting the model to the CORI and SEER data, we learn biologically relevant parameters, including the transition rate from adenoma to cancer. The inferred parameters allow us to predict the individualized risk of the presence of cancer cells for each screened patient. We provide a web application which allows the user to calculate these individual probabilities at https://ccrc-eth.shinyapps.io/CCRC/. For example, we find a 1 in 100 chance of cancer given the presence of an adenoma between 10 and 20mm size in an average risk patient at age 50. We show that our two-type branching process model recapitulates the early growth dynamics of colon adenomas and cancers and can recover epidemiological trends such as adenoma prevalence and cancer incidence while remaining mathematically and computationally tractable.Author summary: Colorectal cancer is a major public health burden. The development of colorectal cancer starts with the mutational initiation of non-cancerous growths in the form of benign adenomatous polyps. These adenomas grow over time with the potential to develop into carcinomas. Many mathematical and simulation-based models have been used to gain insight into this process. We aimed to understand rates of adenoma growth and transition into carcinomas, to enable better planning of colorectal cancer screening strategies. To this end, we expand the two-type branching process model, and fit it on data describing the frequency of sizes of adenomas and carcinomas. The results provide new, data-based, estimates of the rates of development for colorectal cancer.

Suggested Citation

  • Brian M Lang & Jack Kuipers & Benjamin Misselwitz & Niko Beerenwinkel, 2020. "Predicting colorectal cancer risk from adenoma detection via a two-type branching process model," PLOS Computational Biology, Public Library of Science, vol. 16(2), pages 1-23, February.
    • Handle: RePEc:plo:pcbi00:1007552
    DOI: 10.1371/journal.pcbi.1007552
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