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Shape-specific characterization of colorectal adenoma growth and transition to cancer with stochastic cell-based models.
Simonetto, Cristoforo; Mansmann, Ulrich; Kaiser, Jan Christian.
Affiliation
  • Simonetto C; Institute of Radiation Medicine, Helmholtz Munich, Oberschleissheim, Germany.
  • Mansmann U; Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
  • Kaiser JC; Institute of Radiation Medicine, Helmholtz Munich, Oberschleissheim, Germany.
PLoS Comput Biol ; 19(1): e1010831, 2023 01.
Article in En | MEDLINE | ID: mdl-36689547
Colorectal adenoma are precursor lesions on the pathway to cancer. Their removal in screening colonoscopies has markedly reduced rates of cancer incidence and death. Generic models of adenoma growth and transition to cancer can guide the implementation of screening strategies. But adenoma shape has rarely featured as a relevant risk factor. Against this backdrop we aim to demonstrate that shape influences growth dynamics and cancer risk. Stochastic cell-based models are applied to a data set of 197,347 Bavarian outpatients who had colonoscopies from 2006-2009, 50,649 patients were reported with adenoma and 296 patients had cancer. For multi-stage clonal expansion (MSCE) models with up to three initiating stages parameters were estimated by fits to data sets of all shapes combined, and of sessile (70% of all adenoma), peduncular (17%) and flat (13%) adenoma separately for both sexes. Pertinent features of adenoma growth present themselves in contrast to previous assumptions. Stem cells with initial molecular changes residing in early adenoma predominantly multiply within two-dimensional structures such as crypts. For these cells mutation and division rates decrease with age. The absolute number of initiated cells in an adenoma of size 1 cm is small around 103, related to all bulk cells they constitute a share of about 10-5. The notion of very few proliferating stem cells with age-decreasing division rates is supported by cell marker experiments. The probability for adenoma transiting to cancer increases with squared linear size and shows a shape dependence. Compared to peduncular and flat adenoma, it is twice as high for sessile adenoma of the same size. We present a simple mathematical expression for the hazard ratio of interval cancers which provides a mechanistic understanding of this important quality indicator. We conclude that adenoma shape deserves closer consideration in screening strategies and as risk factor for transition to cancer.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Adenoma Type of study: Diagnostic_studies / Etiology_studies / Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans / Male Language: En Journal: PLoS Comput Biol Journal subject: BIOLOGIA / INFORMATICA MEDICA Year: 2023 Document type: Article Affiliation country: Germany Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Adenoma Type of study: Diagnostic_studies / Etiology_studies / Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans / Male Language: En Journal: PLoS Comput Biol Journal subject: BIOLOGIA / INFORMATICA MEDICA Year: 2023 Document type: Article Affiliation country: Germany Country of publication: United States