-Dr. Brenner and Dr. Shuryak Awarded NASA Grant
Dr. David Brenner and Dr. Igor Shuryak were recently awarded a NASA grant to study the physical and biological modulators of space radiaiton carcinogenesis through mechanistically-based model development.
The project, Physical and Biological Modulators of Space Radiation Carcinogenesis: Mechanistically-Based Model Development for Space Radiation Risk Assessment, is designed to use state-of-the-art mechanistic modeling of the experimental data from NSCOR programs and other available data as a basis to generate HZE related cancer risk and uncertainty estimates in humans. There are four components: First, development of practical mechanistically-motivated models, emphasizing the significance of individual radiation sensitivity. Second, based on model-based analysis of our and other NSCOR experimental data, estimate site-specific and consensus quality functions for HZE ions. Third, generate realistic uncertainty estimates for these estimates. Finally, our results and uncertainties will be critically compared with the current NASA projections and uncertainties.
Briefly, carcinogenesis and pre-carcinogenesis data will be analyzed using a “multi-stage + genomic instability” biological model for the age-dependent background cancer rate. The HZE and γ radiation modifications of these background risks will initially be modeled with a mechanistically-based testable approach, in which the cancer incidence rate for an individual age A exposed to an acute radiation fluence φ increases from the background rate, λ(A), to λ(A+κφ), where κ is radiation-quality and cancer-type dependent.
For RBE estimation we will use a new approach, initially suggested by Kellerer and Walsh (1), and subsequently by the ICRP (2), to estimating low-dose HZE cancer risk in humans. Here the HZE human cancer risk is derived from two quantities: 1) the epidemiologically-determined low-LET excess relative risk at an intermediate dose (an appropriate γ-ray dose here is 2 Gy), and 2) the estimated RBE, derived from HZE animals studies, relative to this single acute 2 Gy γ-ray dose. This approach considerably reduces the final uncertainties, compared with traditional methodologies.
We will be analyzing the data from the NSCOR programs at Georgetown (GI carcinogenesis), as well as at UT Southwestern (breast carcinogenesis), and will extend the analyzed results to other HZE ion (or ions) of interest. We will primarily use the microdosimetric approach initially suggested by Zaider and Brenner (3) and Bond et al (4) and in ICRU Report 40 (5), and now used extensively by other groups in radiotherapy contexts.
Our quality function estimates and corresponding uncertainties will be compared with the current NASA risk projections and uncertainties (6). When there are differences, the origin of these differences will be assessed, in terms of potentially a) the different data sets analyzed, b) the different models applied, and c) the different low-LET base data used.
1. Kellerer AM, Walsh L. Risk estimation for fast neutrons with regard to solid cancer. Radiat Res 2001; 156:708-17.
2. ICRP. Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (wR). Report 92 of the International Commission on Radiological Protection. Ann ICRP 2003; 33:1-117.
3. Zaider M, Brenner DJ. On the microdosimetric definition of quality factors. Radiat Res 1985; 103:302-16.
4. Bond VP, Varma MN, Sondhaus CA, Feinendegen LE. An alternative to absorbed dose, quality, and RBE at low exposures. Radiat Res Suppl 1985; 8:S52-7.
5. ICRU, The Quality Factor in Radiation Protection. International Commission on Radiation Units and Measurements, Bethesda, MD, 1986.
6. Cucinotta FA, Kim M-HT, Chappell LJ, Space Radiation Cancer Risk Projections and Uncertainties - 2012. NASA Report NASA/TP-2013-217375, 2013.