Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies

Abstract

Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

FIG. 1

Category-specific relative risks for thyroid radiation dose for all data (solid circle) with selected 95% CIs, for non-CCSS data (star) and CCSS data for those who were (open triangle) or were not (open square) treated with chemotherapy, and the 4-parameter fitted dose-response model to all data (solid line) and to non-CCSS data only (dash line). Display includes full range of doses.

FIG. 2

Category-specific relative risks for thyroid radiation dose for all data (solid circle) and the 4-parameter fitted dose-response model to all data (solid line) and a power (dash line) and linear (dash-dot-dot line) model to doses ≤2 Gy, with an additive adjustment for use of chemotherapy. For the power model, 0.01 Gy replaced zero doses and the plot is adjusted to reflect the case-weighted category-specific relative risk of 2.82 at a mean dose of 0.10 Gy. Plot uses the same aspect ratio as Fig. 1.

FIG. 3

Category-specific relative risks for thyroid radiation dose for all data (solid circle) and the 4-parameter fitted dose-response model to all data (solid line) and a power (dash line) and linear (dash-dot-dot line) model to doses ≤0.10 Gy, with an additive adjustment for use of chemotherapy. For the power model, 0.01 Gy replaced zero doses and the plot is adjusted to reflect the case-weighted category-specific relative risk of 1.22 at a mean dose of 0.02 Gy. Plot uses the same aspect ratio as Fig. 1.