Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Endocr Relat Cancer. 2013 Sep 3;20(5):717-24. doi: 10.1530/ERC-13-0021. Print 2013 Oct.
The familial risk of medullary thyroid carcinoma (MTC alone or as part of multiple endocrine neoplasms, MEN2A/MEN2B) is high, so we aimed to answer open questions about the lifetime cumulative risk of thyroid cancer (LCRTC at 0-79 years) among relatives of MTC patients by age and sex. For this nationwide study, a cohort of 3217 first-/second-degree relatives (FDRs/SDRs) of 389 MTC patients diagnosed in 1958-2010 in the Swedish Family-Cancer Database was followed for the incidence of thyroid cancer. The LCRTC in female relatives of patients with early-onset MEN2B (diagnosis age <25 years) was 44-57%, representing 140-520 times increase over the risk in their peers without a family history of endocrine tumors (men: LCRTC=22-52%, 320-750 times) depending on the number of affected FDRs/SDRs. The LCRTC in female relatives of patients with late-onset MEN2B (diagnosis age ≥25 years) was about 15-43% (men=24%). The LCRTC among relatives of early-onset MTC-alone patients was 3-20%. The LCRTC among relatives of late-onset MTC-alone patients was 5-26%. The LCRTC in female relatives of MEN2A patients was 16-63% (men=52%). The relatives of patients with early-onset MTC exhibited a high tendency to develop early-onset thyroid cancer. Simply available data on the number of FDRs and even SDRs affected with MTC and their age at diagnosis were quite informative for the estimation of the risk of thyroid cancer in probands. In settings where genetic testing is not available or affordable for all, evidence-based cumulative risks reported in this nationwide study may help physicians to identify very high-risk individuals.
甲状腺髓样癌（MTC 单独或作为多发性内分泌肿瘤的一部分，MEN2A/MEN2B）的家族风险较高，因此我们旨在回答有关 MTC 患者亲属一生中甲状腺癌（0-79 岁时的 LCRTC）累积风险的未决问题，按年龄和性别划分。在这项全国性研究中，我们对 389 例于 1958 年至 2010 年在瑞典家族癌症数据库中诊断出的 MTC 患者的 3217 名一级/二级亲属（FDRs/SDRs）进行了随访，以了解甲状腺癌的发病率。早发性 MEN2B（诊断年龄<25 岁）患者的女性亲属的 LCRTC 为 44-57%，与无内分泌肿瘤家族史的同龄人相比，风险增加了 140-520 倍（男性：LCRTC=22-52%，320-750 倍），具体取决于受影响 FDRs/SDRs 的数量。晚发性 MEN2B（诊断年龄≥25 岁）患者的女性亲属的 LCRTC 约为 15-43%（男性=24%）。早发性 MTC 单独患者亲属的 LCRTC 为 3-20%。晚发性 MTC 单独患者亲属的 LCRTC 为 5-26%。MEN2A 患者的女性亲属的 LCRTC 为 16-63%（男性=52%）。早发性 MTC 患者的亲属有发展为早发性甲状腺癌的高倾向。有关 FDR 数量的简单信息，甚至是受 MTC 影响的 SDR 数量及其诊断年龄，对于估计先证者的甲状腺癌风险非常有帮助。在无法或负担不起对所有人进行基因检测的情况下，本全国性研究报告的基于证据的累积风险可能有助于医生识别高危个体。
