Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family.
Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family.
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BRCA1 和 BRCA2 的外显率估计基于临床癌症遗传学服务环境中的基因检测：所引用的乳腺癌/卵巢癌风险应反映家庭中的癌症负担。
DOI：
10.1186/1471-2407-8-155
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发表时间：
2008-05-30
期刊：
影响因子：
3.8
通讯作者：
Maher ER
中科院分区：
文献类型：
--
作者：
Evans DG;Shenton A;Woodward E;Lalloo F;Howell A;Maher ER
家族性乳腺癌激酶中BRCA 1或BRCA 2突变的鉴定允许对有风险的亲属进行基因检测。然而，关于家族突变检测呈阳性的妇女的癌症风险存在相当大的争议。我们回顾了385个不相关的家庭（223个BRCA 1和162个BRCA 2突变），通过两个区域癌症遗传学服务确定。我们估计了女性突变携带者（904名已证实的突变携带者-总共1442名女性假设携带突变）中乳腺癌和卵巢癌的发病率，并评估了突变位置和出生队列对发病率的影响。BRCA 1组70岁和80岁的乳腺癌发病率分别为68%（95%CI 64.7-71.3%）和79.5%（95%CI 75.5-83.5%），BRCA 2组分别为75%（95%CI 71.7-78.3%）和88%（95%CI 85.3-91.7%）。BRCA 1组70岁和80岁时的卵巢癌风险分别为60%（95%CI 65-71%）和65%（95%CI 75-84%），BRCA 2组分别为30%（95%CI 25.5-34.5%）和37%（95%CI 31.5-42.5%）。这些风险是通过对家族中癌症的前瞻性研究和未受影响亲属的基因检测来证实的。我们还发现了强队列效应的证据，1940年以后出生的女性到40岁时患乳腺癌的累积风险为22%，而1930年以前出生的女性这一风险为8%（p = 0.0005）。在遗传学服务环境中选择的高风险家庭中，家族性BRCA 1/BRCA 2突变检测阳性的妇女可能具有累积的乳腺癌风险，这与最初从大家庭获得的估计一致。1940年以后出生的女性尤其如此。
The identification of a BRCA1 or BRCA2 mutation in familial breast cancer kindreds allows genetic testing of at risk relatives. However, considerable controversy exists regarding the cancer risks in women who test positive for the family mutation. We reviewed 385 unrelated families (223 with BRCA1 and 162 with BRCA2 mutations) ascertained through two regional cancer genetics services. We estimated the penetrance for both breast and ovarian cancer in female mutation carriers (904 proven mutation carriers – 1442 females in total assumed to carry the mutation) and also assessed the effect on penetrance of mutation position and birth cohort. Breast cancer penetrance to 70 and to 80 years was 68% (95%CI 64.7–71.3%) and 79.5% (95%CI 75.5–83.5%) respectively for BRCA1 and 75% (95%CI 71.7–78.3%) and 88% (95%CI 85.3–91.7%) for BRCA2. Ovarian cancer risk to 70 and to 80 years was 60% (95%CI 65–71%) and 65% (95%CI 75–84%) for BRCA1 and 30% (95%CI 25.5–34.5%) and 37% (95%CI 31.5–42.5%) for BRCA2. These risks were borne out by a prospective study of cancer in the families and genetic testing of unaffected relatives. We also found evidence of a strong cohort effect with women born after 1940 having a cumulative risk of 22% for breast cancer by 40 years of age compared to 8% in women born before 1930 (p = 0.0005). In high-risk families, selected in a genetics service setting, women who test positive for the familial BRCA1/BRCA2 mutation are likely to have cumulative breast cancer risks in keeping with the estimates obtained originally from large families. This is particularly true for women born after 1940.
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影响因子：
158.5
作者：
Meijers-Heijboer, H;van Geel, B;Klijn, JGM
通讯作者：
Klijn, JGM
影响因子：
64.8
作者：
WOOSTER, R;BIGNELL, G;STRATTON, MR
通讯作者：
STRATTON, MR
影响因子：
4
作者：
Evans, DGR;Eccles, DM;Lalloo, F
通讯作者：
Lalloo, F
影响因子：
4
作者：
Smith, A.;Moran, A.;Evans, D. G. R.
通讯作者：
Evans, D. G. R.
影响因子：
158.5
作者：
Struewing, JP;Hartge, P;Tucker, MA
通讯作者：
Tucker, MA