Page 403 - 2014 Printable Abstract Book
P. 403
biomarker into epidemiology for improved risk estimation and modelling of radiation-induced
carcinogenesis. For this purpose we characterized the radiation-associated expression of CLIP2 by
immunohistochemistry and confirmed CLIP2 overexpression also at the protein level. Further, we
developed a standardized workflow for CLIP2 typing in PTC. Finally, we characterized the function of CLIP2
by reconstructing the CLIP2 associated gene regulatory network from global gene expression data derived
from clinical samples of radiation-associated PTCs as well as from an in vitro model of CLIP2 perturbed
PTC cells (knock-down and overexpression). The resulting integrated CLIP2 interactome provides
functional and mechanistic insights into the role of CLIP2 and its impact on radiation-induced
carcinogenesis.
(SNF05) Potential radiation-induced genomic instability in the Swedish hemangioma cohort and
1
3
2
1
consequences for breast cancer risk. Markus Eidemuller ; Erik Holmberg ; Peter Jacob ; Marie Lundell ;
1
and Per Karlsson, 2 Helmholtz Zentrum Muenchen, Neuherberg, Germany ; Sahlgrenska University
3
Hospital, Göteborg, Sweden ; and Karolinska University Hospital, Stockholm, Sweden
2
Breast cancer incidence among 17,200 female Swedish hemangioma patients is analyzed with
biologically-based models of carcinogenesis. The patients were treated in infancy mainly by external
application of radium-226. A total of 877 breast cancer cases have been observed with a follow-up until
2009. A re-evaluation of the dose estimates resulted in substantial dose reduction for a part of the highly
exposed women. Compared to previous analyses of the Swedish hemangioma cohort, the changes in
dose estimates increase the central value of the excess relative risk by a factor of two. No dependence of
ERR on attained age is observed. The data were analyzed with mechanistic models of carcinogenesis
including a separate path of genomic instability. The analysis shows that the path of genomic instability is
significantly enhanced after radiation exposure. Consequences of this potential role of radiation-induced
genomic instability for breast cancer risk is presented. The effect of genomic instability on different
transition rates in the process of carcinogenesis is estimated.
carcinogenesis. For this purpose we characterized the radiation-associated expression of CLIP2 by
immunohistochemistry and confirmed CLIP2 overexpression also at the protein level. Further, we
developed a standardized workflow for CLIP2 typing in PTC. Finally, we characterized the function of CLIP2
by reconstructing the CLIP2 associated gene regulatory network from global gene expression data derived
from clinical samples of radiation-associated PTCs as well as from an in vitro model of CLIP2 perturbed
PTC cells (knock-down and overexpression). The resulting integrated CLIP2 interactome provides
functional and mechanistic insights into the role of CLIP2 and its impact on radiation-induced
carcinogenesis.
(SNF05) Potential radiation-induced genomic instability in the Swedish hemangioma cohort and
1
3
2
1
consequences for breast cancer risk. Markus Eidemuller ; Erik Holmberg ; Peter Jacob ; Marie Lundell ;
1
and Per Karlsson, 2 Helmholtz Zentrum Muenchen, Neuherberg, Germany ; Sahlgrenska University
3
Hospital, Göteborg, Sweden ; and Karolinska University Hospital, Stockholm, Sweden
2
Breast cancer incidence among 17,200 female Swedish hemangioma patients is analyzed with
biologically-based models of carcinogenesis. The patients were treated in infancy mainly by external
application of radium-226. A total of 877 breast cancer cases have been observed with a follow-up until
2009. A re-evaluation of the dose estimates resulted in substantial dose reduction for a part of the highly
exposed women. Compared to previous analyses of the Swedish hemangioma cohort, the changes in
dose estimates increase the central value of the excess relative risk by a factor of two. No dependence of
ERR on attained age is observed. The data were analyzed with mechanistic models of carcinogenesis
including a separate path of genomic instability. The analysis shows that the path of genomic instability is
significantly enhanced after radiation exposure. Consequences of this potential role of radiation-induced
genomic instability for breast cancer risk is presented. The effect of genomic instability on different
transition rates in the process of carcinogenesis is estimated.
