Lifetime cancer risks in individuals with germline PTEN mutations.
Lifetime cancer risks in individuals with germline PTEN mutations.
复制标题
种系PTEN突变患者的终生癌症风险。
DOI：
10.1158/1078-0432.ccr-11-2283
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发表时间：
2012-01-15
期刊：
影响因子：
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通讯作者：
Eng C
中科院分区：
文献类型：
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作者：
Tan MH;Mester JL;Ngeow J;Rybicki LA;Orloff MS;Eng C
年龄调整癌症发病率和年龄相关外显率研究有助于指导癌症风险评估和管理。PTEN错构瘤-肿瘤综合征（PHTS）是一个术语，包括几种PTEN肿瘤抑制基因种系突变的临床综合征亚群。我们进行了第一项前瞻性研究，以阐明相应的癌症风险，揭示人类种系PTEN突变的生物学见解，并根据专家意见更好地告知当前的监测建议。前瞻性招募了3399名符合放宽的国际考登协会PHTS标准的个体；368人被发现有有害的种系PTEN突变。进行年龄校正标准化发病率（SIR）计算和基因型-表型分析。乳腺癌SIRs升高（25.4%,95% c.i.）。19.8-32.0)，甲状腺（51.1,38.1-67.1），子宫内膜（42.9,28.1-62.8），结直肠（10.3,5.6-17.4），肾脏（30.6,17.8-49.4），黑色素瘤（8.5,4.1-15.6）。估计终生风险分别为85.2% (95% ci。71.4% - -99.1%), 35.2%(19.7% - -50.7%), 28.2%(17.1% - -39.3%), 9.0%(3.8 - % 14.1%), 33.6%(10.4% - -56.9%)和6%(1.6% - -9.4%)。启动子突变与乳腺癌有关，而结直肠癌与无义突变有关。携带PTEN突变的患者患多种癌症的终生风险增加，目前已扩展到结直肠癌、肾癌和黑色素瘤。基因型与表型的关联可能为PTEN的结构和功能提供新的见解。我们提出了一种全面的方法来监测PTEN突变患者。
Age-adjusted cancer incidence and age-related penetrance studies have helped guide cancer risk assessment and management. PTEN Hamartoma-Tumor Syndrome (PHTS) is a term encompassing subsets of several clinical syndromes with germline mutations in the PTEN tumor suppressor gene. We conducted the first prospective study to clarify corresponding cancer risks to shed biological insights on human germline PTEN mutations, and to better inform current surveillance recommendations based on expert opinion. A series of 3,399 individuals meeting relaxed International Cowden Consortium PHTS criteria were prospectively recruited; 368 individuals were found to have deleterious germline PTEN mutations. Age-adjusted standardized incidence ratio (SIR) calculations and genotype-phenotype analyses were performed. Elevated SIRs were found for carcinomas of the breast (25.4, 95%C.I. 19.8-32.0), thyroid (51.1, 38.1-67.1), endometrium (42.9, 28.1-62.8), colorectum (10.3, 5.6-17.4), and kidney (30.6, 17.8-49.4), and melanoma (8.5, 4.1–15.6). Estimated lifetime risks were, respectively, 85.2% (95%C.I. 71.4%-99.1%), 35.2% (19.7%-50.7%), 28.2% (17.1%-39.3%), 9.0% (3.8-%14.1%), 33.6% (10.4%–56.9%) and 6% (1.6%-9.4%). Promoter mutations were associated with breast cancer, while colorectal cancer was associated with nonsense mutations. Lifetime risks for a variety of cancers, now extending to colorectal cancer, kidney cancer and melanoma, are increased in patients with PTEN mutations. The genotype-phenotype associations here may provide new insights on PTEN structure and function. We propose a comprehensive approach to surveillance of patients with PTEN mutations.