Maehle Lovise, Apold Jaran, Paulsen Torbjørn, Hagen Bjørn, Løvslett Kjell, Fiane Bent, Van Ghelue Marijke, Clark Neal, Møller Pål
Section for Inherited Cancer, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway.
Clin Cancer Res. 2008 Nov 15;14(22):7569-73. doi: 10.1158/1078-0432.CCR-08-0112.
Inherited ovarian cancer carries a serious prognosis. Prophylactic oophorectomy has been advocated. The degree to which inherited ovarian cancer is restricted to BRCA mutation carriers is not fully known. We wanted to determine the prevalence of BRCA mutation carriers in women at high risk from ovarian cancer.
Healthy women who were found to be at increased risk judged by family history were followed prospectively. Full BRCA1/2 mutation analysis was conducted on all patients who contracted pelvic cancer.
We identified 1,582 women at risk during 5,674 person-years. Forty infiltrating epithelial ovarian cancers, six peritoneal cancers, and one fallopian tube cancer were diagnosed. All but one of these patients (98%) had a BRCA mutation, a frequency that was significantly higher than for the 3 patients with borderline ovarian cancers, who were all mutation negative (P = 0.0002). Eighty-two percent of the detected mutations belonged to one of the 10 Norwegian founder mutations previously reported. At prophylactic bilateral salpingo-oophorectomy, cancer was found in 18 of 345 (5.2%) of mutation carriers compared with none in the 446 mutation negative (P = 0.0000).
In healthy women with a family history of ovarian cancer, high risk for ovarian cancer was restricted to BRCA1/2 mutation carriers. A woman at risk for ovarian cancer according to her family history should have access to full BRCA1/2 mutation testing before deciding on prophylactic bilateral salpingo-oophorectomy.
遗传性卵巢癌预后严重，有人主张进行预防性卵巢切除术。遗传性卵巢癌仅限于携带BRCA突变者的程度尚不完全清楚。我们想确定卵巢癌高危女性中BRCA突变携带者的比例。
对通过家族史判定为风险增加的健康女性进行前瞻性随访。对所有患盆腔癌的患者进行全面的BRCA1/2突变分析。
在5674人年的时间里，我们确定了1582名有风险的女性。诊断出40例浸润性上皮性卵巢癌、6例腹膜癌和1例输卵管癌。除1名患者外，所有这些患者（98%）都有BRCA突变，这一频率显著高于3例卵巢交界性肿瘤患者，这3例患者均为突变阴性（P = 0.0002）。检测到的突变中有82%属于先前报道的10种挪威始祖突变之一。在预防性双侧输卵管卵巢切除术中，345名突变携带者中有18名（5.2%）发现癌症，而446名突变阴性者中未发现癌症（P = 0.0000）。
在有卵巢癌家族史的健康女性中，卵巢癌的高危人群仅限于BRCA1/2突变携带者。根据家族史有卵巢癌风险的女性在决定进行预防性双侧输卵管卵巢切除术之前，应进行全面的BRCA1/2突变检测。
