Heimdal K, Maehle L, Apold J, Pedersen J C, Møller P
Section of genetic counseling, Department of Cancer Genetics, Norwegian Radium Hospital, N-0310 Oslo, Norway.
Eur J Cancer. 2003 Oct;39(15):2205-13. doi: 10.1016/s0959-8049(03)00548-3.
We aimed to describe the penetrances of the four Norwegian founder mutations in BRCA1 (816delGT, 1135insA, 1675delA and 3347delAG) with regard to breast and ovarian cancers in families ascertained through cancer family clinics or a consecutive series of women with breast or ovarian cancer. We have extended the families as far as possible and tested all family members that asked for genetic testing. Penetrance is based upon counting the mutation carriers. The series contains sufficient numbers of mutation carriers to minimise variation in the estimates due to a limited sample set. The penetrances for all four mutations were high, both with respect to breast and ovarian cancers. This is in accordance with other reports from cancer family clinics, but contrasts with reports from population-based series of mutation carriers. Risks of first cancer (breast or ovarian), breast cancer, and ovarian cancer at age 50 years were 43, 30 and 17%, respectively. Corresponding risks at age 70 years were 84, 58 and 58%. Risks for breast cancer before age 30 years and for ovarian cancer before 35 years were low. Penetrances with regard to ovarian cancer were different for the four mutations. The risk of ovarian cancer was doubled in carriers of the 1675delA mutation when compared with the 816delGT mutation (24 versus 12% at age 50 years, P=0.004). The mutations analysed are high penetrance alleles. No differences in penetrance between the series ascertained through the cancer family clinic or the series of consecutive cancer patients was observed. There are discrepancies between our findings and the low penetrances reported for other mutations in other populations. This may be due to methodological differences, but may reflect differences between mutations and/or modifying factors in different populations.
我们旨在描述BRCA1基因中四种挪威始祖突变（816delGT、1135insA、1675delA和3347delAG）在通过癌症家族诊所确诊的家族或一系列连续的乳腺癌或卵巢癌女性患者中，发生乳腺癌和卵巢癌的外显率。我们尽可能地扩展了这些家族，并对所有要求进行基因检测的家族成员进行了检测。外显率是基于对突变携带者的计数得出的。该系列包含足够数量的突变携带者，以尽量减少由于样本集有限而导致的估计值变化。所有四种突变的外显率在乳腺癌和卵巢癌方面都很高。这与癌症家族诊所的其他报告一致，但与基于人群的突变携带者系列报告形成对比。50岁时首次患癌（乳腺癌或卵巢癌）、患乳腺癌和患卵巢癌的风险分别为43%、30%和17%。70岁时的相应风险分别为84%、58%和58%。30岁之前患乳腺癌和35岁之前患卵巢癌的风险较低。四种突变在卵巢癌方面的外显率有所不同。与816delGT突变相比，1675delA突变携带者患卵巢癌的风险增加了一倍（50岁时分别为24%和12%，P = 0.004）。所分析的突变是高外显率等位基因。在通过癌症家族诊所确诊的系列和连续癌症患者系列之间，未观察到外显率的差异。我们的研究结果与其他人群中其他突变报告的低外显率存在差异。这可能是由于方法学差异，但可能反映了不同人群中突变和/或修饰因子的差异。
