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Review
. 2014 May;55(3):391-406.
doi: 10.1093/jrr/rrt133. Epub 2013 Dec 22.

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

Masao S Sasaki  1 , Akira Tachibana, Shunichi Takeda
Affiliations
Review

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

Masao S Sasaki et al. J Radiat Res. 2014 May.

Abstract

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

Keywords: A-bomb survivors; DSB repair pathway choice; artificial neural networks; cancer risk; integrate-and-fire model; low-dose radiation.

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Figures

Fig. 1.
Fig. 1.
Data processing by the ANN method (example). Lung cancer incidence in Hiroshima A-bomb male survivors exposed at ATB (20+). MWA = w1000s50, Dmax= 3 Sv. (a) SRR and SERR are the weighted sum of RR and ERR, respectively, fitted to a polynomial function of dose by maximum likelihood method. (b) The continuous probability density function of ERR (solid line) obtained by calculating S′RR − 1 according to Eq. 4 is compared with the observed ERR data with 80% confidence intervals (CIs) connected by spline interpolation. t1 = 0.32, t2 = 0.55, μ = −0.12. The reference dose–response (dotted line) is calculated according to: y(x > t2) = (0.359 ± 0.066)x + (0.219 ± 0.066)x2.
Fig. 2.
Fig. 2.
Solid cancers by city and gender. (a) All solid cancers in a combined Hiroshima and Nagasaki cohort (T). Panel 1: SRR and SERR. Panel 2: ERR. (b) City-based difference of all solid cancers. (c) Difference by city for ERR for lung cancer. (d) Difference by city for ERR for liver cancer. (e) Difference by city for ERR for gallbladder cancer. (f) Gender difference for ERR for all solid cancers in Hiroshima. (g) Gender difference for ERR for all solid cancers in Nagasaki. (h) City- and gender-adjusted ERR for all solid cancers in general populations with anticipated 1:1 gender ratio. H = Hiroshima, N = Nagasaki, T = two cities combined, M = male. F = female.
Fig. 3.
Fig. 3.
Difference in ERR by gender and organ (Hiroshima). (a) Oral cancer. (b) Esophageal cancer. (c) Stomach cancer. (d) Colorectal cancer. (e) Pancreatic cancer. (f) Gallbladder cancer. (g) Liver cancer. (h) Lung cancer. (i) Thyroid cancer. (j) Cancer of urinary system. (k) Skin cancer (non-melanoma). (l) Brain cancer (cancer of central nervous system). (m) Prostate cancer. (n) Breast and cervical cancer. (o) Ovarian cancer. M = male, F = female.
Fig. 4.
Fig. 4.
Liquid cancer. (a) City differences for ERR. (b) Gender difference for ERR in Hiroshima. (c) Gender difference for ERR in Nagasaki (including factory workers) (N − a). (d) Gender difference for ERR in Nagasaki (excluding factory workers) (N − b). (e) The dose–responses after city- and gender-adjustment. For Nagasaki, adjustments were made using non-factory workers. M = male, F = female, H = Hiroshima, N = Nagasaki, T = two cities combined.
Fig. 5.
Fig. 5.
Effects of ATB (Hiroshima). (a) Solid cancers. (b) Liquid cancers. Panel 1 shows SERR and Panel 2 shows ERR at each ATB. (c) ERR for solid cancers for ATB (0–20). (d) ERR for solid cancers for ATB (20–30). (e) ERR for liquid cancers for ATB (0–20). (f) ERR for liquid cancers for ATB (20–30). M = male, F = female.
Fig. 6.
Fig. 6.
Distribution of SIR and SMR of solid cancers with ground distance from the hypocenter. (a) SIR standardized by NIC as the reference population (not normalized). (b) SIR standardized by NIC as the reference population (normalized by farthest value set at SIR = 1). (c) SMR standardized by nominal control population (<0.005 Gy) as the reference population (normalized by farthest value being set at SMR = 1). Arrows indicate the critical distance beyond which no survivors were exposed to doses of x ≥ 0.005 Gy.
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