Page 86 - 2014 Printable Abstract Book
P. 86
(S2302) Epidemiologic studies integrating biology and radiation measurement. Jonine Bernstein,
Memorial Sloan Kettering Cancer Institute, New York, NY
Few epidemiologic studies on radiation effects for cancer and non-cancer outcomes have
successfully incorporated biologic measures with sound epidemiologic methods and radiation
measurements. Within the context of providing an overview of the few studies conducted to date, this
talk will focus on the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study, an
international multi-center population-based case-control study designed specifically to examine the joint
roles of interaction of gene carrier status and radiation exposure in the etiology of breast cancer. The
study population, includes 1,508 women with asynchronous contralateral breast cancer (CBC) who serve
as cases and 2,200 women with unilateral breast cancer (UBC) who serve as matched controls. The
underlying hypothesis is that a woman who carries certain genetic mutations will be more susceptible to
radiation-associated breast cancer than a woman who is not a carrier. Biologic specimens are obtained
from each woman, each woman is interviewed, and medical records are used to reconstruct the location-
specific radiation dose received to the contralateral breast. A genetic profile for each women is obtained,
i.e., the germline (inherited) characteristics of major breast cancer genes such as BRCA1, BRAC2, and ATM,
and contrasted with estimated dose. New findings relating to risk of developing CBC among carriers of
mutations in the ATM (for ataxia-telangiectasia mutated) gene who were treated with radiation for their
first primary breast cancer will be discussed with a view to understanding low dose-response relationships
in carcinogenesis and the interplay of genetic susceptibility.
(S2303) Integrating Basic Radiobiological Science and Epidemiological Studies (RRS/NCRP Symposium):
Clinical Relevance. Simon Powell, Memorial Sloan Kettering Cancer Center, New York, NY
The major biological effects of ionizing radiation are mediated through DNA damage. The lethal
consequences of ionizing radiation are due to how the DNA damage is processed, either by DNA repair or
triggering cell death. There are effects of ionizing radiation that may be mediated by non-nuclear effects,
in particular damage to the cell membrane that can trigger cell death in certain tissue types.
Epidemiological studies demonstrate short and long-term consequences of ionizing radiation. Short-term
effects tend to be from high dose effects of radiation, which are not seen outside of the use of either
nuclear weapons or nuclear accidents. Clinical use of radiation therapy delivers high doses of radiation to
selected volumetric targets within the body, which creates different dose-relationships than is observed
for whole body irradiation. A surprising feature of radiation exposure, which is not well understood, is
why the same dose of radiation can produce a widely differing severity of responses in the exposed normal
tissues. The predisposition to radiation-induced cancers seen in large population studies could potentially
extrapolate into characteristics that predict for side effects of therapeutic radiation. Although there are
non-genetic components that contribute to individual variations in radiation sensitivity, the predominant
driver is thought to be genetic. In order to understand the nature of individual differences in the radiation
damage response or radiation sensitivity, we tested the DNA damage response of the 1000 Genomes
lymphoblastoid cell lines in order to elucidate genetic loci linked to the response to ionizing radiation.
Although there are difficulties with carrying out a genome wide association study, we have identified a
number of loci and target genes that have naturally occurring polymorphisms that may drive radiation
sensitivity in epidemiologic studies as well as in clinical radiation tolerance. Using a high-throughput assay
based on γH2AX, we have observed a naturally occurring 3-fold range of sensitivity to radiation. We are
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Memorial Sloan Kettering Cancer Institute, New York, NY
Few epidemiologic studies on radiation effects for cancer and non-cancer outcomes have
successfully incorporated biologic measures with sound epidemiologic methods and radiation
measurements. Within the context of providing an overview of the few studies conducted to date, this
talk will focus on the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study, an
international multi-center population-based case-control study designed specifically to examine the joint
roles of interaction of gene carrier status and radiation exposure in the etiology of breast cancer. The
study population, includes 1,508 women with asynchronous contralateral breast cancer (CBC) who serve
as cases and 2,200 women with unilateral breast cancer (UBC) who serve as matched controls. The
underlying hypothesis is that a woman who carries certain genetic mutations will be more susceptible to
radiation-associated breast cancer than a woman who is not a carrier. Biologic specimens are obtained
from each woman, each woman is interviewed, and medical records are used to reconstruct the location-
specific radiation dose received to the contralateral breast. A genetic profile for each women is obtained,
i.e., the germline (inherited) characteristics of major breast cancer genes such as BRCA1, BRAC2, and ATM,
and contrasted with estimated dose. New findings relating to risk of developing CBC among carriers of
mutations in the ATM (for ataxia-telangiectasia mutated) gene who were treated with radiation for their
first primary breast cancer will be discussed with a view to understanding low dose-response relationships
in carcinogenesis and the interplay of genetic susceptibility.
(S2303) Integrating Basic Radiobiological Science and Epidemiological Studies (RRS/NCRP Symposium):
Clinical Relevance. Simon Powell, Memorial Sloan Kettering Cancer Center, New York, NY
The major biological effects of ionizing radiation are mediated through DNA damage. The lethal
consequences of ionizing radiation are due to how the DNA damage is processed, either by DNA repair or
triggering cell death. There are effects of ionizing radiation that may be mediated by non-nuclear effects,
in particular damage to the cell membrane that can trigger cell death in certain tissue types.
Epidemiological studies demonstrate short and long-term consequences of ionizing radiation. Short-term
effects tend to be from high dose effects of radiation, which are not seen outside of the use of either
nuclear weapons or nuclear accidents. Clinical use of radiation therapy delivers high doses of radiation to
selected volumetric targets within the body, which creates different dose-relationships than is observed
for whole body irradiation. A surprising feature of radiation exposure, which is not well understood, is
why the same dose of radiation can produce a widely differing severity of responses in the exposed normal
tissues. The predisposition to radiation-induced cancers seen in large population studies could potentially
extrapolate into characteristics that predict for side effects of therapeutic radiation. Although there are
non-genetic components that contribute to individual variations in radiation sensitivity, the predominant
driver is thought to be genetic. In order to understand the nature of individual differences in the radiation
damage response or radiation sensitivity, we tested the DNA damage response of the 1000 Genomes
lymphoblastoid cell lines in order to elucidate genetic loci linked to the response to ionizing radiation.
Although there are difficulties with carrying out a genome wide association study, we have identified a
number of loci and target genes that have naturally occurring polymorphisms that may drive radiation
sensitivity in epidemiologic studies as well as in clinical radiation tolerance. Using a high-throughput assay
based on γH2AX, we have observed a naturally occurring 3-fold range of sensitivity to radiation. We are
84 | P a g e
