前立腺がんの環境・宿主要因に関する疫学的研究

• Project/Area Number: 12218101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: 赤座 英之 筑波大学, 大学院・人間総合科学研究科, 教授 (70010486)
• Co-Investigator(Kenkyū-buntansha): 塚本 泰司 札幌医科大学, 医学部, 教授 (50112454) ; 平尾 佳彦 奈良県立医科大学, 医学部, 教授 (00133207) ; 内藤 誠二 九州大学, 大学院・医学研究院, 教授 (40164107) ; 藤岡 知昭 岩手医科大学, 医学部, 教授 (80173409) ; 森 満 札幌医科大学, 医学部, 教授 (50175634) ; 野口 雅之 筑波大学, 基礎医学系, 教授 (00198582)
• Project Period (FY): 2000 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥103,100,000 (Direct Cost: ¥103,100,000); Fiscal Year 2004: ¥22,300,000 (Direct Cost: ¥22,300,000); Fiscal Year 2003: ¥21,000,000 (Direct Cost: ¥21,000,000); Fiscal Year 2002: ¥20,800,000 (Direct Cost: ¥20,800,000); Fiscal Year 2001: ¥20,000,000 (Direct Cost: ¥20,000,000); Fiscal Year 2000: ¥19,000,000 (Direct Cost: ¥19,000,000)
• Keywords: 前立腺がん / 疫学 / 環境要因 / 宿主要因 / 大豆イソフラボン / エコール / 遺伝子多型 / イソフラボン / 大豆蛋白

Research Abstract

従来の疫学調査から、前立腺がんには生活環境要因と宿主側の要因が強く関与していると考えられている。本研究では前立腺がんの第一次予防戦略の可能性を見出すことを目的とし、環境要因と宿主要因をcase-control studyにより多面的に比較検討している。これまでの生活習慣要因の調査では、魚類および大豆製品はリスクを減少させた。有意ではないものの緑茶もリスクを下げる傾向にあった。他の環境要因では、前立腺肥大の既往歴が有意にリスクを高めた。血中大豆イソフラボン測定では、エコールnon-producerが症例群で有意に多く認められた。国際比較では、日韓に比べて欧米では.血中イソフラボン濃度が低く、エコールproducerの割合が著明に低いことが示された。日本における年代別比較では、50代以上ではエコールproducerが50%であるのに対し、20-40代では20-30%と低下し、10代では0%であった。韓国では日本のような年代差は見られなかった。遺伝子解析では、乳がんとの相関が報告されているHER2/neuの多型が前立腺がんと有意に相関していた。また家族性前立腺がんとの相関が報告されているHPC2/ELAC2の多型が前立腺がんと有意に相関していた。本研究においては、多様な前立腺がんの環境・宿主要因が解明され、特にエコール産生能に関しては、前立腺がんハイリスク群(エコールnon-producer)に対する予防戦略構築の可能性が示唆されている。

Research Products

• [Journal Article] Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility (2005)
  • Author(s): Yokomizo, A.et al.
  • Journal Title: Prostate 62 Pages: 49-53
• [Journal Article] A case-control study of diet and prostate cancer in Japan : possible protective effect of traditional Japanese diet (2004)
  • Author(s): Sonoda, T.et al.
  • Journal Title: Cancer Sci 95 Pages: 238-242
• [Journal Article] Comparisons of percent equol producer between prostate cancer patients and controls (2004)
  • Author(s): Akaza, H.et al.
  • Journal Title: Jpn J Clin Oncol. 34 Pages: 86-89
• [Journal Article] HPC2/ELAC2 Polymorphism Associated with Japanese Sporadic Prostate Cancer (2004)
  • Author(s): Yokomizo, A.et al.
  • Journal Title: Prostate 6 Pages: 248-252
• [Journal Article] Blood Isoflavone Levels during Intake of a Controlled Hospital Diet (2004)
  • Author(s): Takashima, N.et al.
  • Journal Title: J Nutr Sci and Vitaminol. 50 Pages: 246-252
• [Journal Article] Is daidzein non-metabolizer a high risk for prostate cancer? A case-controlled study of serum soybean isoflavone concentration (2002)
  • Author(s): Akaza, H.et al.
  • Journal Title: Jpn J Clin Oncol. 32 Pages: 296-300
• [Publications] Akaza, H. et al.: "Comparisons of percent equol producer between prostate cancer patients and controls : Case-controlled studies in Japanese, Korean, and American residents"Jpn.J.Clin.Oncol.. (In press). (2004)
• [Publications] Miyanaga, N. et al.: "Higher consumption of green tea may enhance equol production"Asian Pacific J.Cancer Prev.. 4. 297-301 (2003)
• [Publications] Elkins, D.A. et al.: "Luteinizing hormone beta polymorphism and risk of familial and sporadic prostate cancer"Prostate. 56. 30-36 (2003)
• [Publications] Sonoda, T. et al.: "A case-control study of diet and prostate cancer in Japan : Possibility of protective effect of traditional Japanese diet"Cancer Sci.. (in press). (2004)
• [Publications] Akaza, H. et al.: "Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB)"Prostate Cancer and Prostatic Diseases. 3. 115-119 (2000)
• [Publications] Akaza, H. et al.: "Is daidzein non-metabolizer a high risk for prostate cancer? ; A case-controlled study of serum soy beans isoflavones concentration"J.Clin.Oncol.. 32. 296-300 (2002)
• [Publications] Akaza H: "Is daidzein non-metabolizer a high risk for prostate cancer?.A case-controlled study of serum soy beans isoflavones concentration"Jpn.J.Clin.Oncol.. 32. 296-300 (2002)
• [Publications] Kitamura H: "Does transurethral resection of the prostate facilitate detection of clinically significant prostate cancer that is missed with systematic sextant and transition zone biopsies?"Int.J.Urol.. 9. 95-99 (2002)
• [Publications] Ozono S: "Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer"Prostate Cancer Prostatic Dis.. 5. 128-131 (2002)
• [Publications] Yang P: "Genetic determinants of lung cancer short-term survival : the role of glutathione-related genes"Lung Cancer. 35. 221-229 (2002)
• [Publications] Takimoto Y: "Genetic heterogeneity of surgically resected prostate carcinomas and their biopsy specimens is related to their histologic differentiation"Cancer. 91. 362-370 (2001)
• [Publications] Tomobe M: "AgNOR count in resting cells (resting NOR) is a new prognostic marker in invasive bladder tumor"Anal Cell Pathol. 22. 193-199 (2001)
• [Publications] Akaza H: "Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl(DMAB)"Prostate Cancer and Prostatic Diseases. 3. 115-119 (2000)
• [Publications] Akaza H: "Early results of LH-RH agonist treatment with or without chlormadimone acetate for hormone therapy of naive localized or locally advanced prostate cancer : a propective and randomized study"The Prostate Cancer Study Group. Jpn J Clin Oncol. 30(3). 131-136 (2000)
• [Publications] Masumori N: "A probasin-large T antigen transgenic mouse line develops prostate. adenocarcinoma and neuroendocrine carcinoma with metastatic potential"Cancer Res. 61. 2239-2249 (2001)
• [Publications] Migita T: "The accumulation of angiostatin-like fragments in human prostate carcinoma"Cancer Res. 7. 2750-2756 (2001)
• [Publications] Akaza H: "Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB)"Prostate Cancer and Prostatic Diseases. 3・1. 115-119 (2000)
• [Publications] Shimazui T: "Alterations in expression of cadherin-6 and E-cadherin during kidney development and in renal cell carcinoma."Eur Urol. 38・3. 331-338 (2000)
• [Publications] Ota T: "Transgenic rats carrying copies of the human c-Ha-ras proto-oncogene exhibit enhanced susceptibili-ty to N-butyl-N-(4-hydroxybutyl) nitrosamine bladder carcinogenesis "Carcinogenesis. 21・7. 1391-1396 (2000)
• [Publications] Akaza H: "Early results of LH-RH agonist treatment with or without chlormadinone acetate for hormone therapy of naive localized or locally advanced prostate cancer : a prospective and randomized study"Jpn J Clin Oncol. 30・3. 131-136 (2000)
• [Publications] Hara M: "Lifestyle-related risk factors for total and cancer mortality in men and women"Environ Health Prev Med. 5・1. 111-117 (2000)
• [Publications] Morikawa W: "Angiostatin generation by cathepsin D secreted by human prostate carcinoma cells"J Biol Chem. 275・49. 38912-38920 (2000)