Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA.
Radiat Res. 2012 Oct;178(4):365-76. doi: 10.1667/rr2889.1. Epub 2012 Aug 2.
Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors.
儿童癌症的五年生存率现在超过了 70-80%。儿童时期接触辐射是已知的甲状腺致癌因素；然而，对于高剂量的剂量反应、剂量反应关系的修饰因子以及放射治疗和化学疗法的联合效应的评估，数据是有限的。为了解决这些问题，我们汇集了两项队列研究和两项儿童癌症幸存者的嵌套病例对照研究，包括 16757 名患者，其中 187 名患有原发性甲状腺癌。未接受放射治疗的患者中，接受烷化剂、蒽环类药物或博来霉素治疗的患者甲状腺癌的相对风险（RR）及其 95%置信区间（CI）分别为 3.25（0.9-14.9）、4.5（1.4-17.8）和 3.2（0.8-10.4），且随着辐射剂量的增加而降低（RR 趋势，P = 0.02、0.12 和 0.01）。<10 Gy 的辐射剂量相关 RR 呈近似线性增加，在 10-30 Gy 之间稳定在 10-15 倍，然后下降，但仍高于 50 Gy 剂量。10 Gy 处的拟合 RR 为 13.7（95%CI：8.0-24.0）。与剂量相关的超额 RR 随着暴露时年龄的降低而增加（P < 0.01），但与获得的年龄或暴露后时间无关，暴露后 25 年以上仍保持升高。性别和治疗次数并未改变辐射效应。放射治疗后几十年，甲状腺癌风险仍然升高，这突显了对儿童癌症幸存者进行持续随访的必要性。
