2001 年度実績報告書

乳がんの遺伝子診断とその臨床応用

研究課題

研究課題/領域番号	12217075
研究機関	大阪大学
研究代表者	野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)
研究分担者	田口哲也大阪大学, 医学系研究科, 講師 (80243260) 玉木康博大阪大学, 医学系研究科, 助教授 (10273690)
キーワード	乳癌 / 遺伝子診断 / 予後 / 化学療法感受性 / 易罹患性
研究概要	乳癌診療に遺伝子診断を導入することによって、従来の画像診断や病理診断では知り得ない癌の悪性度、進行度、化学療法感受性等に関する情報を獲得することができ、癌の個性に基づいたより的確な治療(tailored medicine)を実践することが可能になると期待される。本研究の目的は、既存の診断法では限界がありより正確な診断が臨床上切に求められている以下の領域に遺伝子診断を導入し、その臨床的意義を検証することである。(1)乳癌の予後診断:17番染色体の数的異常(monosomy)、および、BRCA2mRNA、wt-1 mRNA、steroid sulfatase mRNAの発現は、それぞれ古典的な予後因子(腫瘍径、リンパ節転移、組織学的異型度等、ER)とは独立した予後因子であった。また、2412個の遺伝子発現解析によって予後不良な乳癌症例を選別することができた。(2)乳癌の化学療法感受性の診断: Docetaxel(DOC)を不活化するCYP3A4の乳癌組織内での発現がDOC耐性の指標として有用であること、また、BRCA1 mRNAの発現が、CE療法(cyclophosphamide+epirubicin)の効果予測因子として有用であることが示唆された。(3)乳癌の易罹患性の診断: CYP17のpromoter領域に存在するSNP、CYP19のexon2のSNPとintron4のTTTA repeat、および、ER-αのpromoter領域に存在するTA repeat(n=13)が乳癌の罹患リスクと相関することが判明した。

研究成果

(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] Miyoshi, Y., et al.: "Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers"Int.J.Cancer. 92. 370-373 (2001)
[文献書誌] Tsukamoto, F., et al.: "Clinicopathological analysis of breast cancers with chromosomal aneusomy detected by fluorescence In situ hybridization"Cancer. 93. 165-170 (2001)
[文献書誌] Motomura, K., et al.: "Combination techinique is superior to dye alone in identification of the sentinel dode in breast cancer patients"J.Surg.Oncol. 76. 96-99 (2001)
[文献書誌] Egawa, C., et al.: "Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characteristics"Jpn.J.Cancer Res.. 92・6. 624-630 (2001)
[文献書誌] Egawa, C., et al.: "Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancers"Int.J.Cancer. 95・4. 255-259 (2001)
[文献書誌] Takamura, Y., et al.: "Prediction of chemotherapeutic response by technetium 99m-MIBI scintigraphy in breast cancer patients"Cancer. 92・2. 232-239 (2001)
[文献書誌] Motomura, K., et al.: "Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients"Eur.J.Surg.Onco.. 27・2. 141-145 (2001)
[文献書誌] Takami, S., et al.: "Chromosomal instability detected by fluorescence in situ hybridization in Japanese breast cancer patients"Clin.Chim.Acta. 308. 127-131 (2001)
[文献書誌] 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"Cancer Lett.. 170・1. 91-97 (2001)
[文献書誌] Ooka, M., et al.: "Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer"Breast Cancer Res Treat. 67・2. 169-175 (2001)
[文献書誌] Miyoshi, Y., et al.: "Clinicopathological characteristics of estrogen receptor-beta positive human breast cancers"Jpn.J.Cancer Res.. 92. 1057-1061 (2001)
[文献書誌] Miyoshi, Y., et al.: "Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer"Int.J.Cancer. 97. 129-132 (2001)
[文献書誌] Egawa, C., et al.: "Quantitative Analysis of Estrogen Receptor-alpha and -beta Messenger RNA Expression in Normal and Malignant Thyroid Tissues by Real-time Polymerase Chain Reaction"Oncology. 61. 293-298 (2001)
[文献書誌] Miyoshi, Y., et al.: "Involvement of 17beta-Hydroxysteroid dehydrogenase up-regulation in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers"Int.J.Cancer. 94. 685-689 (2001)
[文献書誌] Takamura, Y., et al.: "Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers"Int.J.Cancer. (in press).
[文献書誌] Egawa, C., et al.: "High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients"Int.J.Cancer. (in press).
[文献書誌] Shimazu, K., et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentinel lymph node biopsy in breast cancer patients"Surgery. (in press).
[文献書誌] Miyoshi, Y., et al.: "Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women"Breast Journal. (in press).
[文献書誌] Miyoshi, Y., et al.: "Acceleration of chromosomal instability of BRCA1-associated hereditary breast cancers by p53 abnormality"Breast Journal. (in press).

2001 年度 実績報告書

乳がんの遺伝子診断とその臨床応用

研究代表者

野口 眞三郎 大阪大学, 医学系研究科, 教授 (10303942)

研究成果

[文献書誌] Miyoshi, Y., et al.: "Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers"Int.J.Cancer. 92. 370-373 (2001)

[文献書誌] Tsukamoto, F., et al.: "Clinicopathological analysis of breast cancers with chromosomal aneusomy detected by fluorescence In situ hybridization"Cancer. 93. 165-170 (2001)

[文献書誌] Motomura, K., et al.: "Combination techinique is superior to dye alone in identification of the sentinel dode in breast cancer patients"J.Surg.Oncol. 76. 96-99 (2001)

[文献書誌] Egawa, C., et al.: "Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characteristics"Jpn.J.Cancer Res.. 92・6. 624-630 (2001)

[文献書誌] Egawa, C., et al.: "Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancers"Int.J.Cancer. 95・4. 255-259 (2001)

[文献書誌] Takamura, Y., et al.: "Prediction of chemotherapeutic response by technetium 99m-MIBI scintigraphy in breast cancer patients"Cancer. 92・2. 232-239 (2001)

[文献書誌] Motomura, K., et al.: "Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients"Eur.J.Surg.Onco.. 27・2. 141-145 (2001)

[文献書誌] Takami, S., et al.: "Chromosomal instability detected by fluorescence in situ hybridization in Japanese breast cancer patients"Clin.Chim.Acta. 308. 127-131 (2001)

[文献書誌] 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"Cancer Lett.. 170・1. 91-97 (2001)

[文献書誌] Ooka, M., et al.: "Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer"Breast Cancer Res Treat. 67・2. 169-175 (2001)

[文献書誌] Miyoshi, Y., et al.: "Clinicopathological characteristics of estrogen receptor-beta positive human breast cancers"Jpn.J.Cancer Res.. 92. 1057-1061 (2001)

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

[文献書誌] Egawa, C., et al.: "Quantitative Analysis of Estrogen Receptor-alpha and -beta Messenger RNA Expression in Normal and Malignant Thyroid Tissues by Real-time Polymerase Chain Reaction"Oncology. 61. 293-298 (2001)

[文献書誌] Miyoshi, Y., et al.: "Involvement of 17beta-Hydroxysteroid dehydrogenase up-regulation in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers"Int.J.Cancer. 94. 685-689 (2001)

[文献書誌] Takamura, Y., et al.: "Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers"Int.J.Cancer. (in press).

[文献書誌] Egawa, C., et al.: "High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients"Int.J.Cancer. (in press).

[文献書誌] Shimazu, K., et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentinel lymph node biopsy in breast cancer patients"Surgery. (in press).

[文献書誌] Miyoshi, Y., et al.: "Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women"Breast Journal. (in press).

[文献書誌] Miyoshi, Y., et al.: "Acceleration of chromosomal instability of BRCA1-associated hereditary breast cancers by p53 abnormality"Breast Journal. (in press).

2001 年度実績報告書

野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)