| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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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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