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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

Interaction perspective plots in B+. For all solid cancers in B+, the ecdos and dose versions of P5a and P5s (Table 2) are fitted. The top row shows RR (z-axis) as a joint function of ecdos or dose (y-axis) and agex or since (x-axis), at age 70. Below, RR is shown as a function of ecdos or dose and age, at agex 35 or since 35. Shadings from purple to gold show increasing RR
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Fig5: Interaction perspective plots in B+. For all solid cancers in B+, the ecdos and dose versions of P5a and P5s (Table 2) are fitted. The top row shows RR (z-axis) as a joint function of ecdos or dose (y-axis) and agex or since (x-axis), at age 70. Below, RR is shown as a function of ecdos or dose and age, at agex 35 or since 35. Shadings from purple to gold show increasing RR

Mentions: Interactions in B+ are shown by perspective plots in Fig. 5, fitting P5a and P5s with either ecdos or dose, and fixing age = 70 or agex = 35 or since = 35. Figure 6 shows RR /10 mGy and 90% CIs at age 70, using P5a and P5s fitted over A+, B+ and C+. With P5a at age 70 RR increases with agex at all doses in A+-, B+- or C+-. With P5s at age 70, RR decreases (or is constant) with since at all doses. The decrease is confined to since > 35 in C+-. With P5a at agex 35 RR generally decreases (or is constant) with age. With P5s at since 35 RR increases (or is constant) with age in A+- and B+-, but decreases with age at higher doses in C+-.Fig. 5


Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model
Interaction perspective plots in B+. For all solid cancers in B+, the ecdos and dose versions of P5a and P5s (Table 2) are fitted. The top row shows RR (z-axis) as a joint function of ecdos or dose (y-axis) and agex or since (x-axis), at age 70. Below, RR is shown as a function of ecdos or dose and age, at agex 35 or since 35. Shadings from purple to gold show increasing RR
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Interaction perspective plots in B+. For all solid cancers in B+, the ecdos and dose versions of P5a and P5s (Table 2) are fitted. The top row shows RR (z-axis) as a joint function of ecdos or dose (y-axis) and agex or since (x-axis), at age 70. Below, RR is shown as a function of ecdos or dose and age, at agex 35 or since 35. Shadings from purple to gold show increasing RR
Mentions: Interactions in B+ are shown by perspective plots in Fig. 5, fitting P5a and P5s with either ecdos or dose, and fixing age = 70 or agex = 35 or since = 35. Figure 6 shows RR /10 mGy and 90% CIs at age 70, using P5a and P5s fitted over A+, B+ and C+. With P5a at age 70 RR increases with agex at all doses in A+-, B+- or C+-. With P5s at age 70, RR decreases (or is constant) with since at all doses. The decrease is confined to since > 35 in C+-. With P5a at agex 35 RR generally decreases (or is constant) with age. With P5s at since 35 RR increases (or is constant) with age in A+- and B+-, but decreases with age at higher doses in C+-.Fig. 5

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