2002 Fiscal Year Final Research Report Summary
Idiopathic pulmonary fibrosis and lung cancer
| Project/Area Number |
12670174
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
HIRONAKA Mitsugu Jichi Medical School, The Department of Pathology, Lecturer, 医学部, 講師 (60322393)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAYAMA Masashi Jichi Medical School, The Department of Pathology, Graduate School of Medicine, University of Tokyo, Professor, 大学院・医学系研究科, 教授 (70281293)
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| Project Period (FY) |
2000 – 2002
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| Keywords | IPF / Lung Cancer / Constitutional factor / Gene promotor hypermethylation / K-ras mutation |
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| Research Abstract |
It has been reported that the risk of lung cancer is high in patients with idiopathic pulmonary fibrosis(IPF). To elucidate the mechanisms, we performed two studies : (1) genetic polymorphisms related to the detoxication and metabolism of polycyclic aromatic hydrocarbons ; (2) gene promoter hypermethylation and K-ras mutation
(1) The results of genetic polymorphisms related to the detoxication and metabolism of polycyclic aromatic hydrocarbons : We examined genetic polymorphisms of CYP1A1, Glutathione S-transferase M1(GSTM1), and microsomal epoxide hydrolase(mEH) exon 3 and 4 by using PCR-based RFLP method. DNA was obtained from sections of archival tissue samples without nepolastic changes or peripheral blood samples of IPF patients(n=7l), lung cancer without IPF ones(n=123), and healthy volunteers(n=103). The proportion of homozygous variant for mEH exon3 was commonly high in the IPF group(49%, p<0.000l)) and lung cancer group(40%, p=0.0009), compared to the control group(20%).
(2) The results of gene promoter hypermethylation and K-ras muation : We analyzed the promoter hypermethylation of the p16, MGMT, DAP-kinase, RASSFlA, GSTP1, and APC genes by using methylation specific PCR method, and K-ras mutation by using PCR-based SSCP method. DNA was extracted from sections of archival tissue samples of the IPF group(n=44) and lung cancer without IPF group(n=40). The proportion of hypermethylation of MGMT, RASSF1A, and APC in the IPF changes was significant higher than that of the normal lung changes of the lung cancer group (18% vs 0%, 20% vs 0%, and 30% vs 0%, respectively). No K-ras mutation was detected in the IPF lesions.
The downregulation of mEH exon3 related to the detoxication and metabolism of polycyclic aromatic hydrocarbons might play an importnant factor to the IPF onset. In addition, the hypermethylation state of IPF lesion is possible to cause the lung cancer in patients with IPF.
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