Contribution of BRCA1 mutations to ovarian cancer
Contribution of BRCA1 mutations to ovarian cancer
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DOI：
10.1056/nejm199704173361602
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发表时间：
1997-04-17
影响因子：
158.5
通讯作者：
Ponder, BAJ
中科院分区：
文献类型：
--
作者：
Stratton, JF;Gayther, SA;Ponder, BAJ
背景 BRCA1 基因的遗传性突变导致某些家庭患乳腺癌和卵巢癌的风险较高。为了确定一般人群中 BRCA1 突变对卵巢癌的影响，我们分析了在一个中心连续一系列患有卵巢癌的女性的 DNA 样本。方法我们研究了 374 名 70 岁之前被诊断为上皮性卵巢癌并于 1993 年 7 月至 1995 年 9 月期间在皇家马斯登医院接受治疗的女性。通过多重异源双链分析对基因组 DNA 进行了分析。通过测序进一步鉴定变体。 结果 在 374 名女性中，有 13 名被鉴定出可能存在种系 BRCA1 突变（3%；95% 置信区间，2% 至 6%）。其中六个变体以前未曾描述过。在 13 个突变中，有 12 个预计会产生截短的蛋白质产物。另一个变体导致推定的锌指结构域之外的框内删除。 12 名具有截短突变的女性中有 9 人有乳腺癌或卵巢癌或两者都有家族史。 结论 假设我们的方法的灵敏度为 70%，则在 70 岁之前诊断出卵巢癌的女性中，大约有 5%（95% 置信区间，3% 至 8%）发生 BRCA1 突变。 (C) 1997 年，马萨诸塞州医学会。
Background Inherited mutations in the BRCA1 gene confer a high risk of breast and ovarian cancer in some families. To determine the contribution of BRCA1 mutations to ovarian cancer in the general population, we analyzed DNA samples from a consecutive series of women with ovarian cancer seen at one center.Methods We studied 374 women who received a diagnosis of epithelial ovarian cancer before the age of 70 years and were treated at the Royal Marsden Hospital between July 1993 and September 1995. Genomic DNA was analyzed by multiplex heteroduplex analysis. Variants were further identified by sequencing.Results Probable germ-line BRCA1 mutations were identified in 13 of the 374 women (3 percent; 95 percent confidence interval, 2 to 6 percent). Six of the variants have not been described previously. Of the 13 mutations, 12 are predicted to result in a truncated protein product. An additional variant results in an in-frame deletion just outside the putative zinc-finger domain. Nine of the 12 women with truncating mutations had family histories of breast or ovarian cancer or both.Conclusions Assuming that our method has a sensitivity of 70 percent, mutations in BRCA1 occur in approximately 5 percent (95 percent confidence interval, 3 to 8 percent) of women in whom ovarian cancer is diagnosed before the age of 70 years. (C) 1997, Massachusetts Medical Society.