Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene
Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene
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DOI：
10.1086/345310
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发表时间：
2003-01-01
影响因子：
9.8
通讯作者：
Eeles, RA
中科院分区：
文献类型：
--
作者：
Edwards, SM;Kote-Jarai, Z;Eeles, RA
对乳腺癌家族的研究表明，BRCA 2突变的男性携带者患前列腺癌的风险增加，特别是在早期。为了评估BRCA 2突变对早发性前列腺癌的影响，我们对263名年龄小于或等于55岁的前列腺癌患者进行BRCA 2完整编码序列的生殖系突变筛查。在6名男性中发现了蛋白质截短突变（2.3%; 95%置信区间0.8%-5.0%），并且所有这些突变都聚集在卵巢癌聚集区之外。在56岁之前，有害生殖系BRCA 2突变导致前列腺癌的相对风险是23倍。其中4名突变患者没有乳腺癌或卵巢癌家族史。还确定了22个不确定意义的变体。这些结果证实了BRCA 2是一个高风险的前列腺癌易感基因，并对患者及其亲属的早发性前列腺癌的管理具有潜在的意义。
Studies of families with breast cancer have indicated that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age. To evaluate the contribution of BRCA2 mutations to early-onset prostate cancer, we screened the complete coding sequence of BRCA2 for germline mutations, in 263 men with diagnoses of prostate cancer who were less than or equal to55 years of age. Protein-truncating mutations were found in six men (2.3%; 95% confidence interval 0.8%-5.0%), and all of these mutations were clustered outside the ovarian-cancer cluster region. The relative risk of developing prostate cancer by age 56 years from a deleterious germline BRCA2 mutation was 23-fold. Four of the patients with mutations did not have a family history of breast or ovarian cancer. Twenty-two variants of uncertain significance were also identified. These results confirm that BRCA2 is a high-risk prostate-cancer-susceptibility gene and have potential implications for the management of early-onset prostate cancer, in both patients and their relatives.