Biologically-Based Risk Estimation for Radiation-Induced Chronic Myeloid Leukemia. Radiation Carcinogenesis: Applying Basic Science to Epidemiological Estimates of Low-Dose Risks. Overview. Bayesian methods and CML Linear-Quadratic-Exponential model Likelihood and prior data sets
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Biologically-Based Risk Estimation for Radiation-Induced Chronic Myeloid Leukemia
Radiation Carcinogenesis: Applying Basic Science to Epidemiological Estimates of Low-Dose Risks
Using the BCR-ABL to CML
waiting time density
and the linear model
The LQE model is
Di and Dni are the gamma and neutron doses in gray
N is the number of CML target cells per adult
P(ba|T)is the probability of BCR-ABL given a translocation
This is a one-stage model of carcinogenesis.
aage at diagnosis
bO = observed cases (E = expected background cases based on U.S. incidence rates)
ctsx = average of the times since exposure for the cases
The lifetime excess CML risk in the limit of low -ray doses
BCR-to-ABL 2D distances in lymphocytes
Kozubek et al. (1999) Chromosoma 108: 426-435
din [.01, .025], dx in [.04, .05], d in [.05, .06]
G=35 DSB/Gy per cell
6.25 kev/um3 = 1 Gy
R = 3.7 um r0 = 0.24 m, p0 = 0.06
Figure 3: Hypersensitivity ratios in the literature (left panel) and the log-survival dose response for T98G human glioma cells (right panel). Figures from Joiner, M.C., Marples, B., Lambin, P., Short, S.C. and Turesson, I., Low-dose hypersensitivity: current status and possible mechanisms. Int J Radiat Oncol Biol Phys (2001) 49: 379-389.
The net lifetime excess risk of CML is
Letting Dn = 0 while D 0
We solved R0 = 0 for ks as a function of exposure age x.