メイルマノフ セリック   MEIRMANOV Serik    所属   立命館アジア太平洋大学  サステイナビリティ観光学部    職種   教授
言語種別	英語
発行・発表の年月	2008/05
形態種別	論文（学術誌・プロフェショナル誌）
査読	査読あり
標題	Significance of HER2 and C-MYC oncogene amplifications in breast cancer in atomic bomb survivors: associations with radiation exposure and histologic grade.
執筆形態	共著
掲載誌名	Cancer
巻・号・頁	112(10),pp.2143-51
著者・共著者	Miura S, Nakashima M, Ito M, Kondo H, Meirmanov S, Hayashi T, Soda M, Matsuo T, Sekine I.
概要	BACKGROUND: It has been postulated that radiation induces breast cancers in atomic bomb (A-bomb) survivors. Oncogene amplification is an important mechanism during breast carcinogenesis and also serves as an indicator of genomic instability (GIN). The objective of this study was to clarify the association of oncogene amplification in breast cancer in A-bomb survivors with radiation exposure. METHODS: In total, 593 breast cancers were identified in A-bomb survivors from 1968 to 1999, and the association between breast cancer incidence and A-bomb radiation exposure was evaluated. Invasive ductal cancers from 67 survivors and 30 nonsurvivors were analyzed for amplification of the HER2 and C-MYC genes by fluorescence in situ hybridization, and expression levels of hormone receptors were analyzed by immunostaining. RESULTS: The incidence rate increased significantly as exposure distance decreased from the hypocenter (hazard ratio per 1-km decrement, 1.47; 95% confidence interval [95% CI], 1.30-1.66). The incidence of HER2 and C-MYC amplification was increased significantly in the order of the control group, the distal group (P = .0238), and the proximal group (P = .0128). Multivariate analyses revealed that distance was a risk factor for the coamplification of C-MYC and HER2 in breast cancer in survivors (odds ratio per 1-km increment, 0.17; 95% CI, 0.01-0.63). The histologic grade of breast cancers became significantly higher in the order of the control group, the distal group, and the proximal group and was associated with oncogene amplifications. CONCLUSIONS: The current results suggested that A-bomb radiation may affect the development of oncogene amplification by inducing GIN and may be associated with a higher histologic grade in breast cancer among A-bomb survivors.