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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.


Ability to capture a known response. Data is simulated (Appendix B) over B- with RR = 1 + ERR as specified by the formulas in Panels a and c, without interactions. Thick black curves show the true RR. Simulated data is modelled by P2e (Table 2) in Panels a and c, and remodelled by P2d (Table 2) in Panels b and d. At dose = 10, 20... 100 mGy, fitted values and 90% CIs are obtained at each simulation step. Coverage is the % over all 10 doses for which the simulated CI contains the true RR. Panels display the geometric means (hollow dots) interpolated by smoothing splines, green for fitted values, blue (red) for lower (upper) 95% CIs
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Fig4: Ability to capture a known response. Data is simulated (Appendix B) over B- with RR = 1 + ERR as specified by the formulas in Panels a and c, without interactions. Thick black curves show the true RR. Simulated data is modelled by P2e (Table 2) in Panels a and c, and remodelled by P2d (Table 2) in Panels b and d. At dose = 10, 20... 100 mGy, fitted values and 90% CIs are obtained at each simulation step. Coverage is the % over all 10 doses for which the simulated CI contains the true RR. Panels display the geometric means (hollow dots) interpolated by smoothing splines, green for fitted values, blue (red) for lower (upper) 95% CIs

Mentions: Figure 4 displays the simulated geometric mean fitted values and CIs for two of these curves (R1 and C2), showing that the dose model underestimates the true response while the ecdos model captures it correctly.Fig. 4


Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model
Ability to capture a known response. Data is simulated (Appendix B) over B- with RR = 1 + ERR as specified by the formulas in Panels a and c, without interactions. Thick black curves show the true RR. Simulated data is modelled by P2e (Table 2) in Panels a and c, and remodelled by P2d (Table 2) in Panels b and d. At dose = 10, 20... 100 mGy, fitted values and 90% CIs are obtained at each simulation step. Coverage is the % over all 10 doses for which the simulated CI contains the true RR. Panels display the geometric means (hollow dots) interpolated by smoothing splines, green for fitted values, blue (red) for lower (upper) 95% CIs
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Ability to capture a known response. Data is simulated (Appendix B) over B- with RR = 1 + ERR as specified by the formulas in Panels a and c, without interactions. Thick black curves show the true RR. Simulated data is modelled by P2e (Table 2) in Panels a and c, and remodelled by P2d (Table 2) in Panels b and d. At dose = 10, 20... 100 mGy, fitted values and 90% CIs are obtained at each simulation step. Coverage is the % over all 10 doses for which the simulated CI contains the true RR. Panels display the geometric means (hollow dots) interpolated by smoothing splines, green for fitted values, blue (red) for lower (upper) 95% CIs
Mentions: Figure 4 displays the simulated geometric mean fitted values and CIs for two of these curves (R1 and C2), showing that the dose model underestimates the true response while the ecdos model captures it correctly.Fig. 4

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.