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Significance of HER2 and C‐MYC oncogene amplifications in breast cancer in atomic bomb survivors
Author(s) -
Miura Shiro,
Nakashima Masahiro,
Ito Masahiro,
Kondo Hisayoshi,
Meirmanov Serik,
Hayashi Tomayoshi,
Soda Midori,
Matsuo Takeshi,
Sekine Ichiro
Publication year - 2008
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23414
Subject(s) - breast cancer , medicine , oncogene , cancer , incidence (geometry) , odds ratio , oncology , hazard ratio , confidence interval , carcinogenesis , pathology , cell cycle , physics , optics
Abstract 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. Cancer 2008. © 2008 American Cancer Society.