Cancer risk and genotype-phenotype correlations in PTEN hamartoma tumor syndrome
Cancer risk and genotype-phenotype correlations in PTEN hamartoma tumor syndrome
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DOI：
10.1007/s10689-013-9674-3
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发表时间：
2014-03-01
期刊：
影响因子：
2.2
通讯作者：
Vasen, Hans F. A.
中科院分区：
文献类型：
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作者：
Nieuwenhuis, Marry H.;Kets, C. Marleen;Vasen, Hans F. A.
具有生殖系PTEN突变的患者患良性肿瘤和恶性肿瘤的风险很高。我们的目标是评估几种类型的癌症和发育不良的小脑神经节细胞瘤(Lhermitte-Duclos病，LDD)的累积风险。此外，还评估了PTEN错构瘤肿瘤综合征(PHTS)的基因型-表型相关性。PTEN突变患者的数据是从西欧、澳大利亚和美国的临床遗传中心收集的。通过Kaplan-Meier方法计算发生乳腺癌、甲状腺癌、子宫内膜癌、皮肤癌、肾癌、结直肠癌和肺癌以及LDD的累积风险。突变与癌症之间的关联通过卡方检验进行评估。共纳入来自9个国家的180名生殖系PTEN突变携带者，其中81名为男性(45%)。在60岁时，男性罹患癌症和/或腰椎间盘突出症的累积风险为56%，女性为87%(p=0.001)。女性患乳腺癌、甲状腺癌和腰椎间盘突出症的风险显著高于男性。唯一确定的基因型-表型相关性是错义突变患者患甲状腺癌的频率较低(p=0.014)。总而言之，PHTS患者，特别是女性，有很大的风险从广泛的肿瘤谱中发展出一个或多个肿瘤。主要的基因-表型关联尚不能确定。
Patients with germline PTEN mutations are at high risk of developing benign and malignant tumours. We aimed to evaluate the cumulative risk of several types of cancer and of dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease, LDD). In addition, genotype-phenotype correlations in PTEN hamartoma tumour syndrome (PHTS) were assessed. Data on patients with PTEN mutations were collected from clinical genetic centres in Western Europe, Australia, and the USA. The cumulative risk of developing cancers of the breast, thyroid, endometrium, skin, kidneys, colorectum, and lungs, and also LDD was calculated by Kaplan-Meier methods. Associations between mutations and cancer were assessed by Chi square means. A total of 180 germline PTEN mutation carriers, 81 males (45 %), from nine countries were included. The cumulative risk of developing any cancer and/or LDD at age 60 was 56 % for males and 87 % for females (p = 0.001). Females had significant higher risks of developing breast cancer, thyroid cancer, and LDD than males. The only genotype-phenotype correlation identified was a lower frequency of thyroid cancer in patients with missense mutations (p = 0.014). In conclusion, PHTS patients, particularly females, have a substantial risk of developing one or more tumours from a broad tumour spectrum. Major genotype-phenotype associations could not be identified.