Clinical Application of Genetic Diagnosis of Breast Cancer

乳腺癌基因诊断的临床应用

• 批准号: 11307019
• 负责人: NOGUCHI Shinzaburo
• 金额: $ 25.4万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11307019/
• 关键词: Breast cancer; Genetic diagnosis; Nucrinetastasis; BRCA1; BRCA2; Risk assessment; BRCA2; 家族性乳癌; 化学療法感受性; 遺伝子発現プロファイル; 抗癌剤感受性

Summary of our research intended for clinical application of genetic diagnosis of breast cancer is described below : (1) Differential diagnosis of benign and malignant breast tumors by FISH : FISH diagnosis of fine needle aspiration biopsy samples from breast tumors has a diagnostic accuracy comparable to conventional cytology and is useful in making a definitive deagnosis of malignancy in cases with indeterminate and benign cytological results. (2) Diagnosis of prognosis : Bone marrow micrometastases detected by a real-time RT-PCR assay of CK19 or mammaglobin mRNA can serve as a significant prognostic factor being independent of the other conventional prognostic factors. In addition, we have also found that high expression of BRCA2 mRNA or wt-1 mRNA in tumor rtissues is significantly associated with poor prognosis. (3) Genetic diagnosis of familial breast cancer : Fifteen BRCA1 (13.3%) and 21 BRCA2 (18.6%) mutations were identified in 113 Japanese breast cancer families. BRCA1 associated-tumors have been found to have biologically aggressive phenotypes and to show a poorer prognosis as compared with sporadic breast tumors. (4) Genetic polymorphism and breast cancer risk : A significant increase in breast cancer risk (odds ratio = 1.56, P = 0.028) was observed in CYP17^<1931C/C> homozygotes as compared with CYP17^<1931T/C> heterozygotes and CYP17^<1931T/T> homozygotes. Homozygous carriers of the allele with 10 or more TTTA repeats at intron 4 of CYP19 showed a trend toward an increase (OR = 1.80, 95%C.i. = 0.97-3.36) in breast cancer risk.

我们的研究旨在为乳腺癌基因诊断的临床应用总结如下：（1）通过FISH鉴别诊断良性和恶性乳腺肿瘤：从乳腺肿瘤细针穿刺活检样品的FISH诊断具有与常规细胞学相当的诊断准确性，并且对于在不确定和良性细胞学结果的情况下做出恶性肿瘤的明确诊断是有用的。(2)预后诊断：通过CK 19或乳房珠蛋白mRNA的实时RT-PCR检测骨髓微转移可以作为独立于其他常规预后因素的重要预后因素。此外，我们还发现肿瘤组织中BRCA 2 mRNA或wt-1 mRNA的高表达与不良预后显著相关。(3)家族性乳腺癌的基因诊断：在113个日本乳腺癌家族中发现了15个BRCA 1（13.3%）和21个BRCA 2（18.6%）突变。BRCA 1相关肿瘤具有生物学侵袭性表型，与散发性乳腺肿瘤相比，预后较差。(4)基因多态性与乳腺癌风险：与CYP 17 ^<1931 T/C>杂合子和CYP 17 ^<1931 T/T>纯合子相比，CYP 17 ^<1931 C/C>纯合子乳腺癌风险显著增加（比值比= 1.56，P = 0.028）。在CYP 19内含子4上具有10个或更多TTTA重复的等位基因的纯合子携带者显示出增加的趋势（OR = 1.80，95%C.i. = 0.97-3.36）。

项目成果

Miyoshi, Y. et al.: "Acceleration of chromosomal instability by loss of BRCA1 expression and p53 abnormality in sporadic breast cancers"Cancer Lett. 159. 211-216 (2000)

Miyoshi, Y. 等人：“散发性乳腺癌中 BRCA1 表达缺失和 p53 异常加速染色体不稳定”Cancer Lett。

Iwao, K., et al.: "Quantitative analysis of estrogen receptor-α and -βmessenger RNA expression in human breast cancers by real-time polymerase chain reaction"cancers. 89. 1732-1738 (2000)

Iwao, K. 等人：“通过实时聚合酶链式反应对人类乳腺癌中雌激素受体-α 和 -β 信使 RNA 表达进行定量分析”，癌症 89. 1732-1738 (2000)。

Iwao K. et al.: "Quantitative analysis of estrogen receptor-alpha and-beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction"Cencer Lett.. 170. 91-97 (2001)

Iwao K.等人：“通过实时聚合酶链式反应对人类胰腺癌中雌激素受体-α和-β信使RNA表达进行定量分析”Cencer Lett.. 170. 91-97 (2001)

Miyoshi, Y. et al.: "Prediction of response to docetaxel by CYP3A4 mRNA expregsion in breast cancer"Int. J Cancer. 97. 129-132 (2001)

Miyoshi, Y. 等人：“乳腺癌中 CYP3A4 mRNA 表达预测对多西紫杉醇的反应”Int。

Shimazu K. et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentimel lymph node biopsy in breast cancer patients"Surgery,. (in press).

Shimazu K. 等人：“乳晕周围和肿瘤周围注射放射性示踪剂进行乳腺癌患者前哨淋巴结活检的比较”Surgery，。