Women's College Research Institute, University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON, Canada M5G 1N8.
Gynecol Oncol. 2011 May 1;121(2):353-7. doi: 10.1016/j.ygyno.2011.01.020. Epub 2011 Feb 15.
The heritable fraction of ovarian cancer exceeds that of any other common adult cancer. Most inherited cases of ovarian cancer are due to a germline mutation in BRCA1 or BRCA2. It is important to have an accurate estimate of the proportion of ovarian cancer patients who carry a mutation and the specific factors which predict the presence of a mutation.
We tested a population-based series of 1342 unselected patients diagnosed with invasive ovarian cancer between 1995-1999 and 2002-2004 in Ontario, Canada, for germline mutations in BRCA1 and BRCA2. The two genes were tested in their entirety, using a range of techniques, including multiplex ligation-dependent probe amplification (MLPA).
Among the 1342 women, 176 women carried a mutation (107 in BRCA1, 67 in BRCA2, and two in both genes) for a combined mutation frequency of 13.3%. Seven deletions were identified using MLPA (3.9% of all detected mutations). The prevalence of mutations was particularly high among women diagnosed in their forties (24.0%), in women with serous ovarian cancer (18.0%) and women of Italian (43.5%), Jewish (30.0%) or Indo-Pakistani origin (29.4%). A mutation was seen in 33.9% of women with a first-degree relative with breast or ovarian cancer and in 7.9% of women with no first-degree relative with breast or ovarian cancer. No mutation was seen in women with mucinous carcinoma.
BRCA1 and BRCA2 mutations are common in women with invasive ovarian cancer. All women diagnosed with invasive non-mucinous ovarian cancer should be considered to be candidates for genetic testing.
卵巢癌的遗传性比例超过任何其他常见的成人癌症。大多数遗传性卵巢癌是由于 BRCA1 或 BRCA2 的种系突变引起的。准确估计携带突变的卵巢癌患者比例以及预测突变存在的具体因素非常重要。
我们对 1995-1999 年和 2002-2004 年期间在加拿大安大略省诊断为侵袭性卵巢癌的 1342 名未经选择的患者进行了基于人群的系列研究，检测了 BRCA1 和 BRCA2 中的种系突变。使用包括多重连接依赖性探针扩增（MLPA）在内的一系列技术，对这两个基因进行了完整的测试。
在 1342 名女性中，有 176 名女性携带突变（BRCA1 中有 107 名，BRCA2 中有 67 名，两个基因中各有 2 名），总的突变频率为 13.3%。使用 MLPA 发现了 7 个缺失（所有检测到的突变的 3.9%）。四十多岁诊断的女性（24.0%）、浆液性卵巢癌（18.0%）、意大利裔（43.5%）、犹太裔（30.0%）或印度裔巴基斯坦裔（29.4%）的女性突变率特别高。有一级亲属患有乳腺癌或卵巢癌的女性中，有 33.9%发现突变，而没有一级亲属患有乳腺癌或卵巢癌的女性中，有 7.9%发现突变。黏液性癌患者中未见突变。
BRCA1 和 BRCA2 突变在患有侵袭性卵巢癌的女性中很常见。所有诊断为侵袭性非黏液性卵巢癌的女性都应被视为基因检测的候选者。
