BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: Relationship to family history and implications for genetic testing
BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: Relationship to family history and implications for genetic testing
复制标题
DOI：
10.1016/s0002-9378(98)70476-4
复制
发表时间：
1998-04-01
影响因子：
9.8
通讯作者：
Boyd, J
中科院分区：
文献类型：
--
作者：
Rubin, SC;Blackwood, MA;Boyd, J
目的：研究卵巢癌患者中BRCA1、BRCA2和遗传性非息肉病性结直肠癌基因突变的发生率，并评估突变状态与常规获得的癌症家族史之间的关系。研究设计：应用聚合酶链式反应、单链构象多态性分析和基因直接测序的方法，对116例连续接受常规临床治疗的卵巢癌患者进行BRCA1、BRCA2、hMSH2和hMLHI基因突变检测。结果：在116例未经选择的卵巢癌患者中，我们共发现12例患者的13个胚系突变：BRCA1突变10例，hMSH2和hMLHI各1例，1例BRCA2突变发生在1例同时携带BRCA1突变的患者身上。超过一半的BRCA1突变患者有家族史，通常被认为是平淡无奇的。在分析的22个家族史变量中，只有两个变量(母亲乳腺癌或卵巢癌家族史，p=0.037，以及母亲任何癌症家族史，p=0.020)与没有此类病史的卵巢癌患者相比，携带BRCA1突变的风险显著增加。然而，大多数有这些家族史和其他诱导性病史的卵巢癌患者的突变检测结果为阴性。结论：大约10%的卵巢癌发生与已知的易患该疾病的基因突变有关。常规获得的家族史不是识别可能携带突变的患者的可靠方法。大多数有家族病史的卵巢癌患者的已知基因突变检测结果为阴性，这可能表明存在更多的未发现的卵巢癌易感基因。
OBJECTIVE: Our purpose was to determine the prevalence of BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in a large, unselected population of ovarian cancer patients and to evaluate the relationship between mutation status and a routinely obtained family history of cancer.STUDY DESIGN: One hundred sixteen consecutive ovarian cancer patients seen for routine clinical care were examined for BRCA1, BRCA2, hMSH2, and hMLHI gene mutations with use of the polymerase chain reaction, single-strand conformation polymorphism analysis, and direct gene sequencing. Fisher's exact test was used to evaluate possible associations between BRCA1 and BRCA2 mutation status and specific familial characteristics.RESULTS: Among 116 unselected ovarian cancer patients we identified a total of 13 germline mutations in 12 patients: 10 in BRCA1, one each in hMSH2 and hMLHI, and a single BRCA2 mutation, which occurred in a patient also carrying a BRCA1 mutation. More than half the patients with BRCA1 mutations had family histories that would generally be considered unremarkable. Of 22 family history variables analyzed, only two (maternal family history of breast or ovarian cancer, p = 0.037, and maternal family history of any cancer, p = 0.020) conferred a significantly increased risk of carrying a BRCA1 mutation compared with ovarian cancer patients without such a history. However, the majority of ovarian cancer patients with these family histories and other suggestive histories tested negative for mutations.CONCLUSIONS: Approximately 10% of ovarian cancers occur in association with genetic mutations known to predispose to the disease. A routinely obtained family history is an unreliable way to identify patients who might harbor mutations. The majority of ovarian cancer patients with suggestive family histories test negative for known gene mutations, perhaps suggesting the existence of additional undiscovered genes predisposing to ovarian cancer.