Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients
Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients
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DOI：
10.1200/jco.2004.04.179
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发表时间：
2004-05-01
影响因子：
45.3
通讯作者：
Haffty, BG
中科院分区：
文献类型：
--
作者：
Choi, DH;Lee, NH;Haffty, BG
目的 韩国人群中 BRCA 相关乳腺癌的患病率尚未得到广泛评估。方法 对 60 名 40 岁左右患乳腺癌的韩国女性进行研究。通过完整测序，对外周血中的淋巴细胞样本进行 BRCA1 和 BRCA2 检测。获得了三代的家族史。可用石蜡包埋的组织块进行免疫组织化学染色。 结果 在 60 名患者的队列中，9 名患者发现 11 个有害突变（6 个为 BRCA1，5 个为 BRCA2）和 7 个意义不明的错义突变。两名患者的 BRCA1 和 BRCA2 均存在有害突变（双突变）：一半突变是新突变，并且在该队列中未观察到创始人突变。大多数 BRCA 相关患者没有乳腺癌和/或卵巢癌家族史。 BRCA相关肿瘤中HER-2/neu、细胞周期蛋白D1和激素受体的表达较少，p53过表达常见。结论韩国年轻乳腺癌女性中BRCA1和BRCA2突变的患病率较高。然而，正如家庭成员中乳腺癌和卵巢癌发生率较低所证明的那样，外显率似乎较低。这些数据表明，韩国年轻乳腺癌患者中可能存在不同的遗传和病因因素影响 BRCA 基因的传播和外显率。
Purpose The prevalence of BRCA-associated breast carcinoma in the Korean population has not been evaluated extensively.Methods Sixty Korean women who developed breast cancer by age 40 years were studied. Lymphocyte specimens from peripheral blood were processed for BRCA1 and BRCA2 by complete sequencing. Family history through three generations was obtained. Available paraffin-embedded tissue blocks were processed for immunohistochemical staining.Results In the cohort of 60 patients, nine patients with 11 deleterious mutations (six in BRCA1 and five in BRCA2) and seven missense mutations of unknown significance were found. Two patients had deleterious mutations in both BRCA1 and BRCA2 (double mutant): One half of the mutations were novel, and no founder mutations were observed in this cohort. Most of the BRCA-associated patients had no family history of breast and/or ovarian cancer. The expression of HER-2/neu, cyclin D1, and hormone receptors was less common, and p53 overexpression was snore common in BRCA-associated tumors.Conclusion The prevalence of BRCA1 and BRCA2 mutations in Korean women with breast cancer at a young age was high. However, the penetrance, as evidenced by the low frequency of breast and ovarian cancers in family members, appears to be low. These data suggest that there may be different genetic and etiologic factors affecting transmission and penetrance of the BRCA genes in Korean patients with breast cancer diagnosed at a young age.