| Project/Area Number |
14570312
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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 |
Hygiene
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
OYAMA Tsunehiro University of Occupational and Environmental Health, Departments of Environmental Health, Associate professor, 医学部, 助教授 (00309965)
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| Co-Investigator(Kenkyū-buntansha) |
TOYOHI Isse University of Occupational and Environmental Health, Departments of Environmental Health, assistant professor, 医学部, 助手 (80341494)
KAWAMOTO Toshihiro University of Occupational and Environmental Health, Departments of Environmental Health, professor, 医学部, 教授 (60177748)
松本 明子 佐賀医科大学, 医学部, 助手 (10330979)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | CytochromeP450 2A6 / CytochromeP450 2E1 / p53 / Prevention / Lung cancer / Smoking / Survival / CytochromeP450 1A1 / 遺伝子多型 |
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| Research Abstract |
[Introduction] Cytochrome P450 (CYP) 2A6 and CYP2E1 are well-known enzymes that activate procarcinogens, such as the nitrosamines (solvents in tobacco smoke) and that form of DNA adduct. CYP2A6 and CYP2E1 mRNA are also observed in bronchial epithelial cells (BEG). In this study, CYP2A6 and CYP2E1 immunoreactivities in BEC and p53 immunoreactivities in tumor were examined in 78 non-small cell lung cancer (NSCLC) patients. We investigated the relationships between CYP2A6 and CYP2E1 expression in BEC and lifetime cigarette consumption (LTCC). We also revealed the relationships between positive numbers of CYP2A6 and CYP2E1 expression in BEC and LTCC.
[Materials and Methods] We examined CYP2A6 CYP2E1, p53 immunoreactivities in 78 Japanese patients with NSCLC who underwent surgical resection at UOEH after obtaining appropriate informed consent. Histological typing of the tumors was performed according to the WHO classification (adenocarcinoma ; 48 cases, squamous cell carcinoma ; 30 cases). T
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he amount of LTCC classified by the Brinkman Index (BI ; cigarettes/day x years). Immunohistochemical staining (IHC) was performed by the LSAB (labelled streptavidine biotin) method. CYP2A6 and CYP2E1 expression was determined as positive when more than 10% of BEC were stained and p53 expression as positive when more than 10% of tumor cells were stained.
[Results and conclusions] The CYP2A6 and CYP2E1 positive rates in 78 NSCLC were 53% (41/78) and 22% (17/78), respectively. The p53 positive rate was 53% (41/78). The CYP2A6 positive rate (60%) in 30 squamous cell carcinoma seemed to be higher than that (48%) in 48 adenocarcinoma. The p53 positive rate (57%) in 30 squamous cell carcinoma also seemed to be higher than that (50%) in 48 adenocarcinoma. There was a significant relation between CYP2E1 expression and LTCC (p<0.05). There was also a significant relation between positive numbers of CYP expression and LTCC (p<0.05). The CYP2A6 and CYP2E1 positive cases seemed to have shortened survival compared with the CYP2A6 and CYP2E1 negative cases in NSCLC patients with stage I disease.
To study CYP2A6 and CYP2E1 expression in BEC, it may be useful not only accurately to predict the risk of cancer development, but also to formulate individually-tailored plans for cancer prevention. Less
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