BRCA1, BRCA2 and CHEK2 c. 1100 delC mutations in patients with double primaries of the breasts and/or ovaries
BRCA1, BRCA2 and CHEK2 c. 1100 delC mutations in patients with double primaries of the breasts and/or ovaries
复制标题
DOI：
10.1136/jmg.2009.075770
复制
发表时间：
2010-08-01
影响因子：
4
通讯作者：
Wallace, Andrew
中科院分区：
文献类型：
--
作者：
Evans, D. Gareth;Ahmed, Munaza;Wallace, Andrew
背景以往的文献以及BRCA1和BRCA2突变识别风险模型的应用表明，个体中的多原发疾病是BRCA1/2突变的强烈预测因子，并且这比发生在近亲中的相同癌症更具预测性。方法本研究评估了BRCA1、BRCA2和CHEK2c的病理突变检出率。结果与讨论虽然乳腺癌/卵巢双原发癌BRCA1/2基因突变的检出率很高，乳腺癌/卵巢双原发癌高达49%，双侧乳腺癌高达34%，但个体多原发癌的鉴别作用似乎被高估了，特别是在那些只有几种恶性肿瘤的家庭中。尽管如此，在强大的家族聚集性中，双侧乳腺癌确实在不同程度上提高了诊断率。CHEK2 1100Delc突变率在双侧低于单侧，分别为0.8%和2%。在无其他乳腺癌/卵巢癌家族中，孤立的双原发乳腺癌和卵巢癌的突变率为14%(3/22)，而在两个近亲中相同的两个原发癌的突变率为17%(17/99)。如果进一步的研究证实了这些发现，风险模型可能需要调整。
Background Previous publications and utilisation of risk models for BRCA1 and BRCA2 mutation identification suggests that multiple primary disease in an individual is a strong predictor of a BRCA1/2 mutation and that this is more predictive than the same cancers occurring in close relatives.Methods This study assessed the pathological mutation detection rates for BRCA1, BRCA2 and the CHEK2c. 1100 delC mutation in 2022 women with breast cancer, including 100 with breast/ovary double primary and 255 with bilateral breast cancer.Results and discussion Although detection rates for mutations in BRCA1/2 are high at 49% for breast/ovarian double primary and 34% for bilateral breast cancer, the differential effect of multiple primaries in an individual appears to have been overestimated, particularly in those families with only a few malignancies. Nonetheless, bilateral breast cancer does differentially enhance detection rates in strong familial aggregations. CHEK2 1100 DelC mutation rates were lower in bilateral than for unilateral cases at 0.8% compared to 2%. The detected mutation rates for isolated double primary breast and ovarian cancer was 14% (3/22) compared to 17% (17/99) for the same two primaries in two close relatives in families with no other cases of breast/ovarian cancer. Risk models may need to be adjusted if further studies corroborate these findings.