Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
Clin Genet. 2010 Oct;78(4):364-72. doi: 10.1111/j.1399-0004.2010.01473.x.
Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital-based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first-degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first-degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non-carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.
乳腺癌和卵巢癌是白俄罗斯常见的恶性肿瘤，每年分别约有 3500 例和 800 例新发病例。对于乳腺癌，在受切尔诺贝利事故影响不同的地区，发病率和发病年龄似乎存在显著差异。我们评估了三种 BRCA1 种系突变 5382insC、4153delA 和 Cys61Gly 在两个基于医院的系列中的频率和分布：1945 例未经选择的乳腺癌患者和 201 例未经选择的卵巢癌患者，以及来自同一人群的 1019 名健康对照女性。在这些乳腺癌患者中，任何一种突变的发生率为 4.4%，在卵巢癌患者中为 26.4%，在对照组中为 0.5%。在乳腺癌患者中，BRCA1 突变与较早的诊断年龄、雌激素受体（ER）阴性肿瘤以及一级乳腺癌家族史密切相关，尽管只有 35%的 BRCA1 突变携带者有这种家族史。BRCA1 突变在区域分布上没有明显差异，因此，不能用 BRCA1 来解释切尔诺贝利事故受灾地区乳腺癌患者的诊断年龄和家族史的显著差异。接下来，我们观察到白俄罗斯卵巢癌患者系列中 BRCA1 的更高影响和突变谱的转移，其中三种种系突变占 26.4%（53/201）。虽然与同一人群的乳腺癌病例相比，Cys61Gly 突变在卵巢癌中明显较少（p=0.01），但 4153delA 突变对卵巢癌的贡献高于乳腺癌（p<0.01）。BRCA1 突变在一级乳腺癌或卵巢癌家族史的卵巢癌病例中显著富集，而突变携带者和非携带者的卵巢癌诊断中位年龄无差异。综上所述，这些结果确定了三种 BRCA1 种系突变作为白俄罗斯遗传性乳腺癌和卵巢癌易感性的关键组成部分，并可能对该人群的癌症预防、治疗和遗传咨询产生影响。
