title: 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.
authors.affiliation: Helmholtz Zentrum München, Institute of Radiation Protection, 85764 Neuherberg, Germany. Electronic address: markus.eidemueller@helmholtz-muenchen.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Eidemüller
authors.affiliation: Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.affiliation: Helmholtz Zentrum München, Institute of Radiation Protection, 85764 Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Jacob
authors.affiliation: Department of Medical Physics and Oncology, Karolinska University Hospital and Karolinska Institute, SE-171 76 Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Lundell
authors.affiliation: Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Karlsson
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology*; D005260:Female; D042822:Genomic Instability / Q000528:radiation effects*; D006391:Hemangioma / Q000453:epidemiology / Q000532:radiotherapy; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D011829:Radiation Dosage; D012189:Retrospective Studies; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
keywords: Breast cancer risk; Models of carcinogenesis; Radiation-induced genomic instability