Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, Zlotogora J, Heching N, Peretz T
Department of Human Genetics, Hadassah Hebrew University Hospital, Hebrew University Medical School, Jerusalem, Israel.
Am J Hum Genet. 1997 Mar;60(3):505-14.
The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations.
对199名阿什肯纳兹犹太人和44名非阿什肯纳兹犹太无关的乳腺癌和/或卵巢癌患者,分析了BRCA1基因中的185delAG、188del11和5382insC突变以及BRCA2基因中的6174delT突变。在患有卵巢癌的阿什肯纳兹犹太女性中,62%(13/21)有一个目标突变,在40岁之前单独诊断为乳腺癌的女性中有30%(13/43)有该突变,在40岁之后诊断为乳腺癌的女性中有10%(15/141)有该突变。卵巢癌诊断时的年龄与携带状态无关。在99名无乳腺癌和/或卵巢癌家族史的阿什肯纳兹患者中,10%携带其中一种突变;其中两名患者的突变被证明是父系遗传的。一名来自伊拉克的非阿什肯纳兹犹太卵巢癌患者携带185delAG突变。在阿什肯纳兹乳腺癌患者中,185delAG的个体突变频率为6.7%,5382insC为2.2%,6174delT为4.5%;在卵巢癌患者中,185delAG和6174delT的突变频率大致相同(分别为33%和29%),但没有卵巢癌患者携带5382insC突变。由于79%的高发病率乳腺癌家族和35%的高发病率乳腺癌/卵巢癌家族没有这三种已知的始祖突变,因此在该人群中可能还有更多导致遗传性乳腺癌和卵巢癌的突变有待发现。