识别遗传性癌症易感性可促进高风险器官特异性癌症监测和预防。在PTEN错构瘤肿瘤综合征（PHTS）中，纵向研究仍然缺乏，儿童和年轻成年人以及神经发育障碍（NDD）的患者的癌症数据也不足。本研究旨在评估携带生殖系PTEN变异的PHTS患者中，包括第二恶性肿瘤（SMN）在内的终身癌症风险。前瞻性纵向队列研究（2005年9月1日至2022年1月6日）。关于全人群风险的监测、流行病学和最终结果数据库。从北美洲、南美洲、欧洲、澳大利亚和亚洲的社区和学术医疗中心中招募了通过分子学定义为携带生殖系PTEN变异的PHTS患者。数据分析自2022年7月至2023年2月。通过物理和电子病历审核，以及随访通过临床访问或电话采访。相对于全人群的PHTS患者的终身癌症风险。共有7302名患者被前瞻性招募，其中701名患者携带生殖系PTEN变异（同意时的中位数[四分位距]年龄为38[12-52]岁，其中413名女性患者[59％]）。260名患者（37％）获得了纵向跟踪数据，随访中位数（四分位距）为4（2-8）年。在701名患者中，341名（49％）接受了至少1次癌症诊断，其中144名（42％）患有SMN。该研究发现乳腺癌（91％）、子宫内膜癌（48％）、甲状腺癌（33％）、肾癌（30％）和结肠直肠癌（17％）以及黑色素瘤（5％）的终身风险显著升高。在携带PHTS的儿童和年轻成年人（15％）以及神经发育障碍患者（11％）中也观察到了癌症诊断。观察到甲状腺（年龄调整标准化发生率比[ SIR ]，32.1；95％CI，26.0-39.0）、肾（SIR，26.5；95％CI，18.8-36.3）、子宫内膜（SIR，26.0；95％CI，19.5-34.1）、乳腺（SIR，20.3；95％CI，17.3-23.7）和结肠直肠（SIR，7.9；95％CI，5.2-11.7）癌症以及黑色素瘤（SIR，6.3；95％CI，3.5-10.5）的升高风险（P＜.001）。在341名患有PHTS癌症的患者中，有51名（15％）的年龄29岁或以下被诊断出1种或多种癌症，并且其中16人（31.4％）在最后一次随访时患有SMN。发现了23名携带PHTS和癌症的NDD患者，其中5人（22％）在最后一次随访时发生了SMN。与没有NDD的患者相比，患有PHTS和NDD的个体表现出更高的终身癌症风险（危险比，2.7；95％CI，1.7-4.2；P＜.001）。这项队列研究发现了PHTS中持续升高的终身癌症风险。PHTS患者应继续进行特定器官的监测。需要进行更多的研究来确定患有PHTS和NDD的患者的升高癌症风险。

Identifying hereditary cancer predisposition facilitates high-risk organ-specific cancer surveillance and prevention. In PTEN hamartoma tumor syndrome (PHTS), longitudinal studies remain lacking, and there are insufficient data on cancers in children and young adults, as well as individuals with neurodevelopmental disorders (NDD).To evaluate lifetime cancer risks, including second malignant neoplasms (SMN), among patients with PHTS.Prospective longitudinal cohort study (September 1, 2005, through January 6, 2022). General population risks from the Surveillance, Epidemiology, and End Results database. Patients with PHTS, molecularly defined as carrying germline PTEN variants, were accrued from community and academic medical centers throughout North America, South America, Europe, Australia, and Asia. Data were analyzed from July 2022 to February 2023.Review of physical and electronic medical records, and follow-up through clinical visits or telephone interviews.Lifetime cancer risks in PHTS relative to the general population.A total of 7302 patients were prospectively accrued, 701 of whom had germline PTEN variants (median [IQR] age at consent, 38 [12-52] years; 413 female patients [59%]). Longitudinal follow-up data could be obtained for 260 patients (37%), with a median (IQR) follow-up of 4 (2-8) years. Of the 701 patients, 341 (49%) received at least 1 cancer diagnosis, with 144 (42%) of those having SMN. The study found significantly elevated lifetime risks for breast (91%), endometrial (48%), thyroid (33%), kidney (30%), and colorectal cancers (17%), as well as melanoma (5%). Cancer diagnoses were also observed in children and young adults with PHTS (15%) and in patients with PHTS with neurodevelopmental disorders (11%). Elevated risks (P < .001) of thyroid (age-adjusted standardized incidence ratios [SIR], 32.1; 95% CI, 26.0-39.0), kidney (SIR, 26.5; 95% CI, 18.8-36.3), endometrial (SIR, 26.0; 95% CI, 19.5-34.1), breast (SIR, 20.3; 95% CI, 17.3-23.7), and colorectal (SIR, 7.9; 95% CI, 5.2-11.7) cancers, and melanoma (SIR, 6.3; 95% CI, 3.5-10.5) were observed. Of the 341 patients with PHTS with cancer, 51 (15%) had 1 or more cancers diagnosed at age 29 years or younger, and 16 (31.4%) of those developed SMN at final follow-up. Twenty-three patients with PHTS with NDD and cancer were identified, with 5 (22%) having developed SMN at final follow-up. Individuals with PHTS and NDD showed higher lifetime cancer risks compared with individuals with PHTS but without NDD (hazard ratio, 2.7; 95% CI, 1.7-4.2; P < .001).This cohort study found consistently elevated lifetime cancer risks in PHTS. Organ-specific surveillance should continue in patients with PHTS. Additional study is required to ascertain elevated cancer risks in patients with PHTS with NDD.