| Co-Investigator(Kenkyū-buntansha) |
KINJO Takao Univ. of the Ryukyus, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30284962)
MORI Naoki Univ. of the Ryukyus, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (10220013)
SUNAGAWA Hajime Univ. of the Ryukyus, Faculty of Medicine, Professor, 医学部, 教授 (30112452)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
74 cases of multiple cancer in Okinawa from 1986 to 2003 were examined histopathologically. The mean age of the patients was 73 years (from 70 to 91). Molecular analysis of cancer genes (p53, Rb, bc12, cyclins, cdk), mismatch repair genes (hMSH, hMLH and hPMS), HPV, EPV and HTLV-1 infection was also performed.
Of 74 cases, 24 patients with squamons cell carcinoma (SCC) in oral cavity or pharyngeal lesions developed another SCC in different head and neck lesions. 32 cases showed oral SCC and SCC of the lung. The remaining 18 cases were also oral or pharyngeal SCC patients who developed gastric adenocarcinomas (3 cases), uterine cervical (3 cases) and esophageal (3 cases) SCC, and malignant lymphomas (4 cases). Most patients were heavy smokers; only 10 were not smokers.
Out of 56 cases of SCC of the head and neck, HPV (26 cases were type 16 and 38 were type 18) infection was demonstrated. Among them, 54 cases also showed EBV infection (41 were type A and 13 were type B). SCC of the head an
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d neck, including oral and pharymgeal carcinomas occurs with a high incidence in Okinawa, but it is rare on the Japanese mainland. The incidence of such tumors in Okinawa is about 1.5 times higher than that on the mainland.
One lymphoma case developed triple malignant tumors. An infiltrating well differentiated SCC in the maxilla was found at age 52 and an in situ SCC in the tongue 18 years later. Furthermore, at age 72, this patient developed an anaplastic large cell lymphoma. Using PCR, type A EBV infection was demonstrated in the SCC of the maxilla and the tongue, and also the lymphoma. Sequence analysis of the virus revealed a slight difference in the EBNA2 regions between the lymphoma and the SCCs. Thirty bp deletion in the LMP-1 carboxy terminal region was demonstrated in the lymphoma but not in the SCC. HPV and HTLV-1 infection and mismatch repair genes (hMSH, hMLH and hPMS) sequence variation (mutation and deletion) were not detected.
In multiple cancer patients in Okinawa, virus infection was frequently demonstrated, although mismatch repair gene variation was not demonstrated. There is ample evidence indicating that cigarette smoking is the major cause of SCC of the lung as well as the head and neck lesions. It is possible that the recent decrease in the frequency of SCC results at least in part, from changes in smoking habits. The incidence of SCC, however, remains high in Okinawa, and viral infection is still frequently found.
The influence possibly exerted on carcinogens by the metylation in the mismatch repair genes should be the subject of further investigations. Less
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