Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts

Abstract

Context: The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and the radiosensitive thyroid gland.

Objectives: Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray (Gy); evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure.

Design and setting: Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 Gy.

Participants: Cohorts included the following: childhood cancer survivors (n = 2); children treated for benign diseases (n = 6); and children who survived the atomic bombings in Japan (n = 1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in nonirradiated individuals.

Intervention: There were no interventions.

Main outcome measure: Incident thyroid cancers.

Results: For both <0.2 and <0.1 Gy, RRs increased with thyroid dose (P < 0.01), without significant departure from linearity (P = 0.77 and P = 0.66, respectively). Estimates of threshold dose ranged from 0.0 to 0.03 Gy, with an upper 95% confidence bound of 0.04 Gy. The increasing dose-response trend persisted >45 years after exposure, was greater at younger age at exposure and younger attained age, and was similar by sex and number of treatments.

Conclusions: Our analyses reaffirmed linearity of the dose response as the most plausible relationship for "as low as reasonably achievable" assessments for pediatric low-dose radiation-associated thyroid cancer risk.

Figure 1.

Category-specific RR of thyroid cancer by thyroid radiation dose (solid symbol) with 95% CI, a moving-average smoothing (gray line) and ±1 standard deviation (thin gray line), the fitted linear ERR model (solid black line), and a restricted cubic spline (dash-dot-dot line). Data pooled from nine cohort studies and limited to <0.2 Gy (main panel) or <0.1 Gy (inset). Also, the linear-exponential-linear model (Supplemental Appendix) fitted to all data with the full range of doses (dash line).

Figure 2.

Deviances for linear ERR models given a threshold dose (η) (open symbol) (see text for model), with deviances rescaled to zero at the minimum deviance (star symbol) and a moving average smoothing. Dash line identifies one-sided 95% confidence limit. Data pooled from nine cohort studies and limited to <0.2 Gy (main panel) and <0.1 Gy (inset).

Figure 3.

Fitted RRs at 0.2 and 0.1 Gy and 95% CIs under a linear ERR model with effect modification by the natural logarithm of age at exposure divided by 5 years overall and sequentially omitting one study at a time. RRs reflect age 5 years at exposure. Dash line represents lower and upper confidence limits for all data. FR, France; UK, United Kingdom; USA, United States.