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Concepts of association between cancer and ionising radiation: Accounting for specific biological mechanisms.
Radiat. Environ. Biophys. 62, 1-15 (2023)
The probability that an observed cancer was caused by radiation exposure is usually estimated using cancer rates and risk models from radioepidemiological cohorts and is called assigned share (AS). This definition implicitly assumes that an ongoing carcinogenic process is unaffected by the studied radiation exposure. However, there is strong evidence that radiation can also accelerate an existing clonal development towards cancer. In this work, we define different association measures that an observed cancer was newly induced, accelerated, or retarded. The measures were quantified exemplarily by Monte Carlo simulations that track the development of individual cells. Three biologically based two-stage clonal expansion (TSCE) models were applied. In the first model, radiation initiates cancer development, while in the other two, radiation has a promoting effect, i.e. radiation accelerates the clonal expansion of pre-cancerous cells. The parameters of the TSCE models were derived from breast cancer data from the atomic bomb survivors of Hiroshima and Nagasaki. For exposure at age 30, all three models resulted in similar estimates of AS at age 60. For the initiation model, estimates of association were nearly identical to AS. However, for the promotion models, the cancerous clonal development was frequently accelerated towards younger ages, resulting in associations substantially higher than AS. This work shows that the association between a given cancer and exposure in an affected person depends on the underlying biological mechanism and can be substantially larger than the AS derived from classic radioepidemiology.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Assigned Share ; Carcinogenesis ; Probability Of Association ; Radiation Cancer Risk ; Two-stage Clonal Expansion Model; Atomic-bomb Survivors; Breast-cancer; Mutational Signatures; Probability; Risk; Model
ISSN (print) / ISBN
0301-634X
e-ISSN
1432-2099
Quellenangaben
Volume: 62,
Issue: 1,
Pages: 1-15
Publisher
Springer
Publishing Place
One New York Plaza, Suite 4600, New York, Ny, United States
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Medicine (IRM)
Grants
Projekt DEAL