Ionizing radiation induces oncogene amplification, breast cancer
MedWire News: Survivors of the 1945 Nagasaki atomic bomb have an elevated risk for breast cancer, concurrent with amplification of the HER-2 and C-MYC oncogenes, say Japanese researchers who note that women who were closest to the hypocenter carry the greatest risk.
The results support the theory that ionizing radiation, and possibly other carcinogens, cause breast cancer by inducing genomic instability.
The researchers say that radiation induces DNA double-strand breaks in a dose-dependent manner, which are then repaired through nonhomologous end joining and other error-prone mechanisms that can result in rearrangements and amplification of oncogenes.
For the present study, Masahiro Nakashima (Nagasaki University School of Medicine) and colleagues gathered data on 91,890 atomic bomb survivors and stratified them according to their distance from the hypocenter and age at the time of detonation. They also analyzed tumor samples from 67 of these women for various biological markers.
In all, 593 women in the sample have developed breast cancer to date.
Women who were closer to the hypocenter were at significantly greater risk than those further away, as shown by a hazard ratio (HR) of incidence of 1.47 for every 1 km proximal to the hypocenter.
Women who were older at the time of the blast were significantly less likely to develop breast cancer than those who were exposed at a younger age, at a HR of 0.96 for each incremental year.
Fluorescence in situ hybridization of tumor samples revealed that the level of HER2/C-MYC co-amplification was 42.1% in women within 1.5 km of the hypocenter, 6.3% in women 1.5 km or more from the hypocenter, and 4.8% in a group of breast cancer patients from elsewhere in Japan who were not exposed.
Multivariate analyses also demonstrated a positive association between oncogene amplification and higher histologic grade,
"A higher incidence of co-amplification of multiple oncogenes suggests the presence of increased genomic instability in breast cancers arising in survivors who were exposed proximally to the hypocenter," Nakashima and colleagues conclude in the journal Cancer.
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