Multiple primary cancers in families with Li-Fraumeni syndrome
Multiple primary cancers in families with Li-Fraumeni syndrome
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DOI：
10.1093/jnci/90.8.606
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发表时间：
1998-04-15
影响因子：
10.3
通讯作者：
Li, FP
中科院分区：
文献类型：
--
作者：
Hisada, M;Garber, JE;Li, FP
背景：Li-Fraumeni综合征是一种以儿童和年轻人早发性乳腺癌、肉瘤和其他癌症为特征的显性遗传性疾病，患有该综合征的家庭成员也会发生多发性原发癌症，但发病率尚不清楚。为了解决这个问题，我们量化了在1968年至1986年期间最初诊断为癌症的24个Li-Fraumeni类个体的第二和第三原发癌症的发病率。方法：使用康涅狄格州癌症登记处基于人群的发病率数据计算了随后癌症的相对风险（RR）和95%置信区间（ci）。Kaplan-Meier分析用于确定后续癌症的累积概率（+/-标准误差）。结果：在诊断为癌症的200名Li-Fraumeni综合征家庭成员中，30名（15%）发展为第二癌症。8人（4%）患有第三种癌症，而4人（2%）最终患上了第四种癌症。总体而言，第二次癌症发生的RR为5.3 (95% CI = 2.8-7.8)，在第一次癌症诊断后30年，第二次癌症发生的累积概率为57%（+/-10%）。在0-19岁、20-44岁和45岁及以上首次患癌的患者中，该综合征家庭中发生第二次癌症的相对危险度分别为83.0 （95% CI = 36.9-187.6）、9.7 （95% CI = 4.9-19.2）和1.5 （95% CI = 0.5-4.2）。该组42例后续癌症中有30例（71%）为Li-Fraumeni综合征的组成癌。结论：与一般人群相比，Li-Fraumeni综合征家族成员发生多发性原发癌症的风险异常高。额外原发性癌症的额外风险主要针对具有Li-Fraumeni综合征特征的癌症，儿童癌症幸存者的风险最高。这些家庭的癌症幸存者应密切监测新癌症的早期表现。
Background: Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults, Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986, Methods: The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. Results: Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/-10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. Conclusions: Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers.