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Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model

View Article: PubMed Central - PubMed

ABSTRACT

Background: Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour.

Methods: GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 – 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy.

Results: For all solid cancer incidence, RR estimated from 0 – 100 mGy and 0 – 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 – 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort.

Conclusion: Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

Electronic supplementary material: The online version of this article (doi:10.1186/s12940-016-0191-3) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

0 - 400 mGy male and female. For comparison with [8], panel a shows the dose model P5ad (Table 2) fitted to the 0 - 400 mGy male-female data, with knots set at 0, 5, 20, 40, 60, 80, 100, 125, 150, 175, 200, 250, and 300 mGy. Gender averaged RR and 95% CIs are shown at age 70 and agex 30. Panels b and c show the male and female responses. Panel d shows the ecdos model P5ae with corresponding knots at ecdf(dose)(0), ecdf(dose)(5) etc. ML scores and AIC for P5ad and P5ae fitted to the female data are shown for comparison
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Fig13: 0 - 400 mGy male and female. For comparison with [8], panel a shows the dose model P5ad (Table 2) fitted to the 0 - 400 mGy male-female data, with knots set at 0, 5, 20, 40, 60, 80, 100, 125, 150, 175, 200, 250, and 300 mGy. Gender averaged RR and 95% CIs are shown at age 70 and agex 30. Panels b and c show the male and female responses. Panel d shows the ecdos model P5ae with corresponding knots at ecdf(dose)(0), ecdf(dose)(5) etc. ML scores and AIC for P5ad and P5ae fitted to the female data are shown for comparison

Mentions: Furukawa and co-workers [8] analysed the combined male and female incidence data below 400 mGy with models including Linear Non Threshold, cubic smoothing spline, and a Bayesian semiparametric piecewise linear model, with dose responses at age 70, agex 30 shown in their Fig. 1. The Bayesian and spline models gave similar responses at low doses. Whilst comparisons with the Bayesian model are beyond the scope of this paper, the spline model is roughly similar to P5ad, if dose knots are set at 0, 5, 20, 40, 60, 80, 100, 125, 150, 175, 200, 250, and 300 mGy. Furukawa analysed the individual data, but results using P5ad (with these knots) applied to the public data below 400 mGy are not significantly different. Figure 13 (panel) shows the gender averaged dose response for P5ad (knots). The spline estimate in [8] for ERR /100 mGy = 0.03 (CIs are not shown for this model) whilst for P5ad (knots) ERR /100 mGy = 0.07 (0.02, 0.11)95%. The difference might result from the interaction structures in [8] which follow those in [1]. However, as Fig. 13 shows, the male response (panel) lacks 95% significance below ∼ 300 mGy, but (panel) female ERR /100 mGy = 0.11 (0.04, 0.19). Panel shows the ecdos model P5ae with knots corresponding to those chosen for P5ad (knots). Now ERR /100 mGy = 0.17 (0.10, 0.24). With the female data, P5ae (knots) is preferred to P5ad (knots) by ML score and AIC. At 10 mGy with 95% CIs, P5ad (knots) gives ERR /10 mGy = 0.011 (-0.001, 0.023) whilst for P5ae (knots) ERR /10 mGy = 0.052 (0.031, 0.074).Fig. 13


Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model
0 - 400 mGy male and female. For comparison with [8], panel a shows the dose model P5ad (Table 2) fitted to the 0 - 400 mGy male-female data, with knots set at 0, 5, 20, 40, 60, 80, 100, 125, 150, 175, 200, 250, and 300 mGy. Gender averaged RR and 95% CIs are shown at age 70 and agex 30. Panels b and c show the male and female responses. Panel d shows the ecdos model P5ae with corresponding knots at ecdf(dose)(0), ecdf(dose)(5) etc. ML scores and AIC for P5ad and P5ae fitted to the female data are shown for comparison
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5121957&req=5

Fig13: 0 - 400 mGy male and female. For comparison with [8], panel a shows the dose model P5ad (Table 2) fitted to the 0 - 400 mGy male-female data, with knots set at 0, 5, 20, 40, 60, 80, 100, 125, 150, 175, 200, 250, and 300 mGy. Gender averaged RR and 95% CIs are shown at age 70 and agex 30. Panels b and c show the male and female responses. Panel d shows the ecdos model P5ae with corresponding knots at ecdf(dose)(0), ecdf(dose)(5) etc. ML scores and AIC for P5ad and P5ae fitted to the female data are shown for comparison
Mentions: Furukawa and co-workers [8] analysed the combined male and female incidence data below 400 mGy with models including Linear Non Threshold, cubic smoothing spline, and a Bayesian semiparametric piecewise linear model, with dose responses at age 70, agex 30 shown in their Fig. 1. The Bayesian and spline models gave similar responses at low doses. Whilst comparisons with the Bayesian model are beyond the scope of this paper, the spline model is roughly similar to P5ad, if dose knots are set at 0, 5, 20, 40, 60, 80, 100, 125, 150, 175, 200, 250, and 300 mGy. Furukawa analysed the individual data, but results using P5ad (with these knots) applied to the public data below 400 mGy are not significantly different. Figure 13 (panel) shows the gender averaged dose response for P5ad (knots). The spline estimate in [8] for ERR /100 mGy = 0.03 (CIs are not shown for this model) whilst for P5ad (knots) ERR /100 mGy = 0.07 (0.02, 0.11)95%. The difference might result from the interaction structures in [8] which follow those in [1]. However, as Fig. 13 shows, the male response (panel) lacks 95% significance below ∼ 300 mGy, but (panel) female ERR /100 mGy = 0.11 (0.04, 0.19). Panel shows the ecdos model P5ae with knots corresponding to those chosen for P5ad (knots). Now ERR /100 mGy = 0.17 (0.10, 0.24). With the female data, P5ae (knots) is preferred to P5ad (knots) by ML score and AIC. At 10 mGy with 95% CIs, P5ad (knots) gives ERR /10 mGy = 0.011 (-0.001, 0.023) whilst for P5ae (knots) ERR /10 mGy = 0.052 (0.031, 0.074).Fig. 13

View Article: PubMed Central - PubMed

ABSTRACT

Background: Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour.

Methods: GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 – 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy.

Results: For all solid cancer incidence, RR estimated from 0 – 100 mGy and 0 – 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 – 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort.

Conclusion: Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

Electronic supplementary material: The online version of this article (doi:10.1186/s12940-016-0191-3) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus