Breast cancer risk and possible mechanisms of radiation-induced genomic instability in the Swedish hemangioma cohort after reanalyzed dosimetry

Abstract

The cohort of 17,200 female Swedish hemangioma patients, who had been exposed to ionizing radiation because of skin hemangioma, was analyzed for breast cancer incidence with descriptive excess relative risk models and mechanistic models of carcinogenesis. The dosimetry system has recently been updated, leading to substantially reduced doses for the most highly exposed part of the Stockholm cohort. The follow-up includes persons until December 2009 with 877 breast cancer cases. All models agree on the risk estimates. The excess relative and excess absolute risk at the age of 50 years are 0.48 Gy(-1) (95% CI 0.28; 0.69) and 10.4 (10(4)PYR Gy)(-1) (95% CI 6.1; 14.4) (95% CI 6.1; 14.4), respectively. These risk estimates are about a factor of 2 higher than previous analyses of this cohort as a consequence of the re-evaluation of the dosimetry system. Explicit models incorporating effects of genomic instability were developed and applied to the hemangioma cohort. It was found that a radiation-induced transition towards genomic instability was highly significant. The models indicate that the main effect of radiation-induced genomic instability is to increase the rate of transition of non-initiated cells to initiated cells with a proliferative advantage. The magnitude of such an acceleration cannot be inferred from epidemiological data alone, but must be complemented by radiobiological measurements.

New dosimetry for childhood skin hemangioma treatments with 226Ra needles or tubes

“…A risk estimation for female breast cancer for the Swedish Hemangioma Cohort (comprising both the Stockholm and the Gothenburg hemangioma cohorts), made in 2009 [17], gave an Excess Relative Risk (ERR) of 0.25 Gy À1 at the age of 50 years. A new computation with the new breast doses shown here, gave an ERR of 0.48 Gy À1 which is almost twice as high [12]. Our results show the importance of accurate organ dose estimations in retrospective studies which are used for epidemiological investigations of radiation risks.…”

“…the Gothenburg hemangioma study, the French hemangioma study and the Rochester thymus study, the dose values are of the same magnitude. In the Gothenburg study, which is often merged with SHC at various evaluations, the female breast doses were reanalyzed with the MC calculations shown here [12]. The average female breast dose did not change substantially and remained about 0.15 Gy.…”

Are We Approaching the End of the Linear No-Threshold Era?

“…Breast cancer studies, after childhood exposure (64) According to the publication, 3% of women in whole cohort had breast doses exceeding 1 Gy, and mean dose was 0.18 Gy. Thus, cohort included patients with highly carcinogenic doses, even though average dose was much lower.…”

Beyond Two-Stage Models for Lung Carcinogenesis in the Mayak Workers: Implications for Plutonium Risk

“…1. Most premises are motivated by the biological mechanisms thought to underlie GI [14,44]. First, the destabilizing transition rates are set equal, σ j ≡ σ, as they pertain to the inactivation of the same genomic-integrity gene.…”