High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome
High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome
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DOI：
10.1136/jmedgenet-2012-101339
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发表时间：
2013-04-01
影响因子：
4
通讯作者：
Caux, Frederic
中科院分区：
文献类型：
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作者：
Bubien, Virginie;Bonnet, Francoise;Caux, Frederic
PTEN错构瘤肿瘤综合征（PHTS）包括几种PTEN肿瘤抑制基因种系突变的临床综合征，包括以乳腺癌和甲状腺癌风险增加为特征的考登综合征。由于PHTS罕见，有关癌症风险和基因型-表型相关性的数据有限。本研究的目的是根据PTEN突变的类型和位置更好地确定该综合征的癌症风险。方法从法国贝尔戈尼研究所遗传实验室招募携带有害种系PTEN突变的154例PHTS个体。获得了其中146株的详细表型信息。进行了年龄和性别调整的标准化发病率（SIR）计算、累积癌症风险估计和基因型-表型分析。SIRs升高主要见于女性乳腺癌（39.1,95% CI 24.8 ~ 58.6）、女性甲状腺癌（43.2,95% CI 19.7 ~ 82.1）和男性（199.5,95% CI 106.39 ~ 342.03）、女性黑色素瘤（28.3,95% CI 7.6 ~ 35.4）和男性（39.4,95% CI 10.6 ~ 100.9）以及子宫内膜癌（48.7,95% CI 9.8 ~ 142.3）。70岁时任何癌症的累积癌症风险为85% (95% CI为70%至95%)，女性乳腺癌为77% (95% CI为59%至91%)，甲状腺癌为38% （95% CI为25%至56%）。患有PHTS的女性患癌症的风险是患有PHTS的男性的两倍
Background PTEN hamartoma tumour syndrome (PHTS) encompasses several clinical syndromes with germline mutations in the PTEN tumour suppressor gene, including Cowden syndrome which is characterised by an increased risk of breast and thyroid cancers. Because PHTS is rare, data regarding cancer risks and genotype-phenotype correlations are limited. The objective of this study was to better define cancer risks in this syndrome with respect to the type and location of PTEN mutations.Methods 154 PHTS individuals with a deleterious germline PTEN mutation were recruited from the activity of the Institut Bergonie genetic laboratory. Detailed phenotypic information was obtained for 146 of them. Age and sex adjusted standardised incidence ratio (SIR) calculations, cumulative cancer risk estimations, and genotype-phenotype analyses were performed.Results Elevated SIRs were found mainly for female breast cancer (39.1, 95% CI 24.8 to 58.6), thyroid cancer in women (43.2, 95% CI 19.7 to 82.1) and in men (199.5, 95% CI 106.39 to 342.03), melanoma in women (28.3, 95% CI 7.6 to 35.4) and in men (39.4, 95% CI 10.6 to 100.9), and endometrial cancer (48.7, 95% CI 9.8 to 142.3). Cumulative cancer risks at age 70 were 85% (95% CI 70% to 95%) for any cancer, 77% (95% CI 59% to 91%) for female breast cancer, and 38% (95% CI 25% to 56%) for thyroid cancer. The risk of cancer was two times greater in women with PHTS than in men with PHTS (p