Host: The Japan Radiation Research Society
The molecular mechanism of carcinogenesis in atomic-bomb (A-bomb) survivors has not yet been fully understood. Recently, we found RET oncogene amplification (amp) in radiation-induced thyroid cancers, suggesting the involvement of genomic instability (GIN). A radiation etiology is also suggested in breast cancers among survivors. The aim of this study is to clarify the significance of oncogene amp in breast cancers from survivors. A total 593 cases of breast cancers were identified among survivors since 1961 through 1999 based on pathological reports. Total 67 cases of breast cancers from survivors were available in this study. Diagnosis was reviewed and determined histological grade according to a recent criteria. We analyzed the amps of HER2 and C-MYC by FISH and expressions of HER2 and hormone receptors by immunostaining on paraffin-embedded tissues. The incidence rate (IR) of breast cancer was 54.1 per 100,000 PY in survivors. The IR significantly increased as exposure distance decreased from the hypocenter. Incidences of both HER2 and C-MYC amps were significantly higher in proximal distance group (≤1.5km, n=35) than distal (>1.5km, n=32) or control group (others than survivors, n=30). Furthermore, a significant higher incidence of co-amp was found in proximal group as compared to distal or control group. In histological grading, both scores of nuclear size and mitotic counts were significantly higher in proximal group than distal or control group, and significantly correlated with gene amps. These results suggested a significance of A-bomb radiation exposure in HER2 and C-MYC amps in breast cancers from survivors. Gene amp is commonly associated with GIN in solid cancers. In breast cancers from the proximal distance group, the level of GIN might be high and resulted in inducing oncogene amps and tumor progression.