Fries Melissa H, Holt Charlene, Carpenter Isabelle, Carter Cindy L, Daniels Jamelyn, Flanagan Judith, Murphy Kay, Hailey B Jo, Martin Laura, Hume Roderick, Hudson Gracia, Cadman Mary, Weatherly Ronald, Nunes Mark E
Air Force Medical Genetics Center, Keesler Air Force Base, MS 39534, USA.
Mil Med. 2002 Feb;167(2):99-103.
The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.
美国国防部家族性乳腺癌/卵巢癌研究项目已在研究基础上，为符合特定诊断标准的患者提供了BRCA1和BRCA2基因咨询及检测服务，根据库奇模型计算BRCA1和BRCA2突变风险。在2.5年时间里，对250名患者进行了评估，101名患者符合标准要求，其中33名患者符合不止一类标准。90名患者选择接受DNA检测。在这90名患者中，共鉴定出14个突变（15.5%）和16个未分类变异（17.7%）。最常见的纳入标准是45岁前患乳腺癌/卵巢癌（n = 32）以及45岁前患乳腺癌/卵巢癌且有家族病史（n = 21）。然而，当使用卡方统计量分别比较所有诊断标准（包括多种情况的标准）下发现的突变和未分类变异数量时，各标准之间未发现显著差异，这表明没有一种标准比另一种标准更能预测突变或变异。有突变患者的库奇风险值平均为14%，范围在3.2%至43.5%之间（所有患者的范围为1.2%至69.7%）。这些发现强调了使用多种诊断标准的重要性，并表明库奇风险值> 3%可能有助于选择检测患者。数据还强调了基因咨询在检测过程中的必要性，特别是考虑到大量未分类变异的诊断及其疾病易感性的不确定状态。
