Lifetime risks of common cancers among retinoblastoma survivors
Lifetime risks of common cancers among retinoblastoma survivors
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DOI：
10.1093/jnci/djh058
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发表时间：
2004-03-03
影响因子：
10.3
通讯作者：
Peto, J
中科院分区：
文献类型：
--
作者：
Fletcher, O;Easton, D;Peto, J
背景：与普通人群相比，RB 1生殖系突变携带者在视网膜母细胞瘤中存活（即，遗传性视网膜母细胞瘤幸存者）具有增加的早发性第二癌症的风险，特别是肉瘤、脑肿瘤和黑色素瘤。然而，他们对50岁后常见的上皮癌的风险尚不清楚。研究方法：我们使用医院记录来识别1873年至1950年间出生的英国视网膜母细胞瘤幸存者，这一时期很少有英国视网膜母细胞瘤患者接受高剂量放疗。癌症和死亡是通过与国家登记记录联系起来确定的。所有统计检验均为双侧检验。结果：我们可以追踪144名遗传性视网膜母细胞瘤幸存者的癌症病史。从25岁至84岁，有58例后续癌症，累积癌症发病率为68.8%（95%置信区间[CI] = 48.0%至87.4%），累积癌症死亡率为56.3%（95% CI = 40.5%至73.3%）。58种癌症中只有8种是骨或软组织癌症，这与当代对接受外照射治疗的美国患者的研究结果形成鲜明对比，其中大多数第二种肿瘤是肉瘤。与一般人群相比，遗传性视网膜母细胞瘤幸存者肺癌死亡率较高（标准化死亡率[SMR] = 7.01，95% CI = 3.83 - 11.76），膀胱癌（SMR = 26.31，95% CI = 8.54至61.41），以及所有其他上皮癌合并（SMR = 3.29，95% CI = 1.64至5.89）。上皮癌的总体标准化死亡率与年龄的近似平方成反比（年龄指数-2.1，95%CI = -3.6至-0.7），从25-44岁的11.32（95%CI 4.15至24.64）下降至65-84岁的2.83（95%CI = 1.04至6.16）。结论：遗传性视网膜母细胞瘤的幸存者没有暴露于高剂量放射治疗，具有发展为迟发性上皮细胞癌的高终生风险。遗传性视网膜母细胞瘤幸存者的大多数过度癌症风险可能是可以通过限制暴露于DNA损伤剂（放射治疗，烟草和紫外线）来预防的。
Background: Compared with the general population, carriers of germline mutations in RB1 who survive retinoblastoma (i.e., hereditary retinoblastoma survivors) are at increased risk of early-onset second cancers, particularly sarcomas, brain tumors, and melanoma. However, their risks for the epithelial cancers that commonly occur after age 50 years are not known. Methods: We used hospital records to identify British retinoblastoma survivors born between 1873 and 1950, a period when few British retinoblastoma patients received high-dose radiotherapy. Cancers and deaths were identified by linkage with national registration records. All statistical tests were two-sided. Results: We could trace the cancer histories of 144 survivors of hereditary retinoblastoma. From age 25 to age 84, there were 58 subsequent cancers, for a cumulative cancer incidence of 68.8% (95% confidence interval [CI] = 48.0% to 87.4%) and a cumulative cancer mortality of 56.3% (95% CI = 40.5% to 73.3%). Only eight of the 58 cancers were of bone or soft tissue, in marked contrast to findings from contemporary studies of American patients treated with external beam radiotherapy, among whom most second tumors are sarcomas. Compared with the general population, hereditary retinoblastoma survivors had higher mortality from lung cancer (standardized mortality ratio [SMR] = 7.01, 95 % CI = 3.83 to 11.76), bladder cancer (SMR = 26.31, 95% CI = 8.54 to 61.41), and all other epithelial cancers combined (SMR = 3.29, 95% CI = 1.64 to 5.89). The overall standardized mortality ratio for epithelial cancer was inversely proportional to the approximate square of age (exponent of age -2.1, 95 % CI = -3.6 to -0.7), declining from 11.32 (95% CI 4.15 to 24.64) at age 25-44 to 2.83 (95% CI = 1.04 to 6.16) at age 65-84. Conclusions: Survivors of hereditary retinoblastoma who are not exposed to high-dose radiotherapy have a high lifetime risk of developing a late-onset epithelia] cancer. Most of the excess cancer risks in hereditary retinoblastoma survivors might be preventable by limiting exposures to DNA damaging agents (radiotherapy, tobacco, and UV light).