2010 Fiscal Year Final Research Report
Genetic analysis of cancer stems cells in the carcinogenesis and the intractability of treatment of cancer.
Project/Area Number |
20390360
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kyushu University |
Principal Investigator |
INOUE Hiroshi Kyushu University, 生体防御医学研究所・腫瘍外科, 学術研究者(共同研究員) (90203249)
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Co-Investigator(Kenkyū-buntansha) |
MORI Masaki (70190999)
MIMORI Koshi (50322748)
ISHII Hideshi (10280736)
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Project Period (FY) |
2008 – 2010
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Keywords | 遺伝子多型 / 疫学関連因子 / 交互作用 / p53制御分子 |
Research Abstract |
Background : Colorectal cancer (CRC) oncogenesis is considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. Patients and Methods : A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at eleven known single nucleotide polymorphisms (SNPs) and performed GWAS study. TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Then, we performed microarray analysis of genes from cancer cells extracted from 110 primary tumors by laser microdissection. Results : Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (OR=1.16(1.06-1.27), p=0.0015). Non-insulin-dependent diabetes mellitus, a higher body mass index (BMI) at age 20 and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and diabetes had a 1.66 fold higher risk ratio than the cohort of major allele patients without diabetes. Meta-analysis of gene profiles (MetaGP) provide a clew to explain the risk for CRC in major allele at rs6983267 with diabetes mellitus. Conclusion : We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G-allele at the 8q24 rs6983267 SNP, however, a major T-allele SNP could more clearly reveal a correlation with CRC specifically when diabetes mellitus is present. In addition, PICT1 gene, located on 19q13 (CRC oncogenic SNP), a p53 regulating gene, is associated with the progression of CRC and determined prognosis of CRC cases definitely.
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Research Products
(73 results)
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[Journal Article] MicroRNA-125a-5p is an independent prognostic factor in gastric cancer, and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab.2011
Author(s)
Nishida N, Mimori K, Fabbri M, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Mori M.
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Journal Title
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[Journal Article] Kinesin 18A expression clinical relevance to colorectal cancer progression.2011
Author(s)
Nagahara M, Nishida N, Iwatsuki M, Ishimaru S, Mimori K, Tanaka F, Nakagawa T, Sato T, Sugihara K, Hoon DS, Mori M.
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Journal Title
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[Journal Article] Clinical Significance of Stanniocalcin 2 as a Prognostic Marker in Gastric Cancer.2010
Author(s)
Yokobori T, Mimori K, Ishii H, Iwatsuki M, Tanaka F, Kamohara Y, Ieta K, Kita Y, Doki Y, Kuwano H, Mori M
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Journal Title
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[Journal Article] Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles.2010
Author(s)
Tanaka F, Yamamoto K, Suzuki S, Inoue H, Tsurumaru M, Kajiyama Y, Kato H, Igaki H, Furuta K, Fujita H, Tanaka T, Tanaka Y, Kawashima Y, Natsugoe S, Setoyama T, Tokudome S, Mimori K, Haraguchi N, Ishii H, Mori M
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Journal Title
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[Journal Article] CD13 is a therapeutic target in human liver cancer stem cells.2010
Author(s)
Haraguchi N, Ishii H, Mimori K, Tanaka F, Ohkuma M, Kim HM, Akita H, Takiuchi D, Hatano H, Nagano H, Barnard GF, Doki Y, Mori M
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Journal Title
J Clin Invest 120
Pages: 3326-39
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[Journal Article] Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinoma.2009
Author(s)
Kita Y, Mimori K, Tanaka F, Matsumoto T, Haraguchi N, Ishikawa K, Matsuzaki S, Fukuyoshi Y, Inoue H, Natsugoe S, Aikou T, Mori M
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Journal Title
Eur J Surg Oncol 35
Pages: 52-58
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[Journal Article] Loss of FBXW7, a cell cycle regulating gene, in colorectal cancer : Clinical significance.2009
Author(s)
Iwatsuki M, Mimori K, Ishii H, Yokobori T, Takatsuno Y, Sato T, Toh H, Onoyama I, Nakayama KI, Baba H, Mori M
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Journal Title
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[Journal Article] Clinicopathological significance of stanniocalcin 2 gene expression in colorectal cancer.2009
Author(s)
Ieta K, Tanaka F, Yokobori T, Kita Y, Haraguchi N, Mimori K, Kato H, Asao T, Inoue H, Kuwano H, Mori M
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Journal Title
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[Journal Article] A large-scale study of MT1-MMP as a marker for isolated tumor cells in peripheral blood and bone marrow in gastric cancer cases.2008
Author(s)
Mimori K, Fukagawa T, Kosaka Y, Ishikawa K, Iwatsuki M, Yokobori T, Hirasaki S, Takatsuno Y, Sakashita H, Ishii H, Sasako M, Mori M
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Journal Title
Ann Surg Oncol 15
Pages: 2934-2942
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[Journal Article] Fhit-deficient hematopoietic stem cells survive hydroquinone exposure carrying precancerous changes.2008
Author(s)
Ishii H, Mimori K, Ishikawa K, Okumura H, Pichiorri F, Druck T, Inoue H, Vecchione A, Saito T, Mori M, Huebner K
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Journal Title
Cancer Res 68
Pages: 3662-3670
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[Journal Article] Reprogramming of mouse and human cells to pluripotency using mature microRNAs.
Author(s)
Miyoshi N, Ishii H, Nagano H, Haraguchi, Dewi DL, Kano Y Nishikawa S, Tanemura T, Mimori K, Tanaka F, Saito T, Nishimura J, Takemasa I, Mizusima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M.
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Journal Title
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[Journal Article] Regulation of the MDM2-p53 Pathway and Tumor Growth by PICT1/GLTSCR2 via Nucleolar RPL11.
Author(s)
Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, Itoh B, Wangjia J, Komatsu Y, Yang YR, Hikasa H, Horie Y, Yamashita T, Kamijo T, Zhang Y, Prives C, Nakano T, Mak TW, Sasaki T, Maehama T, Mori M, Suzuki A.
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Journal Title
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[Journal Article]
Author(s)
Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, Nozawa K, Ishihara Matsuda KN, Fukushima R, Okinaga K, Sasako M, Mori M.
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Journal Title
J Clin Oncol(Reply to B Faltas et al.) in press
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[Journal Article] Clinical Significance of Circulating Tumor Cells Including Cancer Stem-like Cells in Peripheral Blood for Recurrence and Prognosis in Colorectal Cancer Patients with Dukes stage B and C.
Author(s)
Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, Matsuda K, Fukushima R, Okinaga K, Sasako M, Mori M.
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Journal Title
J Clin Oncol 29
Pages: 1547-1555
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