Beller U, Halle D, Catane R, Kaufman B, Hornreich G, Levy-Lahad E
Division of Gynecologic Surgery and Oncology, Shaare Zedek Medical Center, Jerusalem, 91031, Israel.
Gynecol Oncol. 1997 Nov;67(2):123-6. doi: 10.1006/gyno.1997.4844.
To better understand the role of germline BRCA mutations in ovarian cancer in Ashkenazi Jews, we tested 29 consecutive patients admitted to our service for the three mutations common in this ethnic group. These mutations are 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2. Six patients had both breast and ovarian cancer, and 23 had ovarian cancer only. In the first group, all women had germline mutations, 2 with each mutation. Of 23 ovarian cancer patients, 11 were carriers (48%): 6 of 185delAG, 2 of 5382insC, and 3 of 6174delT. Regarding family history, of 13 women with no family history, 3 (23%) were carriers. Of 10 women with any family history of breast or ovarian cancer, 8 (80%) were carriers. We discuss possible explanations for this surprisingly high carrier rate, including a high proportion of familial disease coupled with lack of adequate family history, lower penetrance than previously expected, or increasing penetrance in recent generations due to nongenetic factors. Our data suggest that genetic testing is merited in all Ashkenazi women with ovarian cancer, regardless of family history.
为了更好地了解阿什肯纳兹犹太人中种系BRCA突变在卵巢癌中的作用，我们对连续收治的29例患者进行了检测，以查找该族群中常见的三种突变。这些突变分别是BRCA1基因的185delAG和5382insC以及BRCA2基因的6174delT。6例患者同时患有乳腺癌和卵巢癌，23例仅患有卵巢癌。在第一组中，所有女性均有生殖系突变，每种突变各2例。在23例卵巢癌患者中，11例为携带者（48%）：185delAG突变携带者6例，5382insC突变携带者2例，6174delT突变携带者3例。关于家族史，在13例无家族史的女性中，3例（23%）为携带者。在10例有乳腺癌或卵巢癌家族史的女性中，8例（80%）为携带者。我们讨论了这种惊人的高携带率的可能原因，包括家族性疾病比例高以及家族史不充分、外显率低于先前预期，或由于非遗传因素导致近几代外显率增加。我们的数据表明，所有患有卵巢癌的阿什肯纳兹女性都值得进行基因检测，无论其家族史如何。
