Low Dose Radiation Effect on Cancer Risk
Analysis of Dose-Response Relationship for Cancer Occurrence among Workers of Nuclear Industry of the Russian Federation: Solving the Problem on the Radiation-Epidemiological and Molecular-Genetic Approach-Based Prediction of Individual Risk
Tech Area / Field
- MED-DIS/Disease Surveillance/Medicine
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
- ENV-MRA/Modelling and Risk Assessment/Environment
3 Approved without Funding
Medical Radiological Scientific Center, Russia, Kaluga reg., Obninsk
- Central Medical Sanitary Institution (CMSI-8), Russia, Kaluga reg., Obninsk\nFEI (IPPE), Russia, Kaluga reg., Obninsk
- Nagasaki University / Graduate School of Biomedical Sciences, Japan, Nagasaki\nNagasaki University / School of Medicine, Japan, Nagasaki
Project summaryIntroduction and review.
The aim of the project is research into effects of ionizing radiation on cancer incidence from small prolonged doses of exposure (below 0.2 Sv). The importance of the problem is obvious; since millions people handling nuclear technologies are exposed to low dose for a long time.
Despite a lot of effort has been put into solving the problem, so far reliable data on the relationship between radiation dose and cancer incidence are absent in the dose interval under consideration. The most of developed standards of radiation protection are based on results derived from cohort study of Japanese atomic bomb survivors (LSS cohort). Statistically reliable data on dose-response relationship was obtained for doses higher than 0.2 Sv [4, 5].
The proposed research into relationship between cancer incidence and dose from ionizing radiation will be carried out by experts of the RNMDR (candidates and doctors of science), who have generally recognized experience in analysis of dose-response relationship for cancer.
It does not raise doubts that key event in malignant transformation of a cell is genetic and structural mutations .
Because somatic mutations play a key part in malignization of cells it is planned to estimate the frequency of different mutations in cells of nuclear workers in relation to radiation dose.
If attributable risk for cancer among nuclear workers has been estimated it will be possible to use inpidual molecular-genetic data for estimation of inpidual risk of cancer.
Subjects of the proposed study are employees of SUE SSC IPPE. The Institute is one of the largest enterprises of nuclear industry in Russia.
The number of employees of SSC IPPE has changed considerably for the period of its operating, it varied from 5 to 10 thousand people, 20% of them were under inpidual dosimetric monitoring. Mean annual dose to a person is 2-3 mSv.
Expected Results and their Application.
The work to be done under the proposed project is related to basic and applied research.
In the category of basic research: analysis of the dose-response relationship will allow estimating radiation risk values and radiation risk coefficients (radiation risk per dose unit). New knowledge about radiobiological effects of low radiation doses on human health and results drawn from the study will allow estimating the effect of radiation at doses of 0.05-1 Gy on genome of somatic cells.
In the category of applied research: cancer occurrence among nuclear workers and non-exposed population of Russia belonged to the same age groups will be compared. Results of the study are suggested to serve as methodological basis for working-out molecular epidemiological approaches to detection of inpiduals at high risk of cancer following the exposure to low dose radiation.
Criteria for selection of group at risk of cancer development based on results of epidemiological and molecular genetic investigation are expected to be worked out.
Realization of the ISTC objectives and tasks:
The proposal conforms fully to the objectives of the ISTC
- Provide weapons scientists in the CIS the opportunity to conduct research directed to peaceful activities
- Foster the integration of scientists from Russia into the global scientific community
- Support basic and applied research and technology development for peaceful purposes: environmental protection, nuclear industry and radiation protection
Scope of activity:
The proposal is a complex of basic and applied research including the following items:
1. Analysis of results of radiation epidemiological studies conducted by scientists of different countries for further estimation of dose-response relationship for cancer incidence caused by low radiation doses.
2. Design of radiation epidemiological cohort study of nuclear workers; design of molecular-genetic study of the group at risk and control group.
3. Retrospective cohort study of cancer incidence among nuclear workers including collection, treatment and verification of inpidual medical, demographic and dosimetric information.
4. Formation of the group at high risk of induction of cancer out of the cohort of nuclear workers based on inpidual attributable risk estimated with UNSCEAR models for further molecular-genetic study. Control group will be selected from the subjects under study.
5. Collection of peripheral blood drawing from the subjects at high risk and controls for molecular genetic studies.
6. Quantitative analysis of gene and structural mutations in nuclear DNA in somatic cells of subjects and controls exposed to low dose and low dose-rate radiation.
7. Evaluation of mutation status of mitochondrial DNA in peripheral blood of "cases" and "controls" exposed to low dose and low dose-rate radiation.
8. Analysis of dose-response relationship for cancer occurrence among nuclear workers exposed to low dose-rate radiation. Determination of inpidual criteria for formation of group at high risk of development of cancer on the basis of results of radiation-epidemiological and molecular genetic studies.
Technical approach and methodology
Cohort method as the most precise one will be applied to the analysis of dose-response relationship for cancer incidence. To calculate radiation risk and its coefficients standard statistical software (EPICURE package) will be used.
Estimates of dose-response relationship for cancer incidence will allow forming the group at risk from healthy people for the molecular genetic investigation.
Specialists of Radiation-Epidemiological Sector of MRRC RAMS involved in the study are experts on Radiation Epidemiology. Radiation-Epidemiological Sector of MRRC RAMS is the only World Health Organization’s collaborative center in Russia in radiation epidemiology.
To investigate genome of somatic cells in exposed people complex approach is suggested to be used. It includes estimation of mutations in nuclear and mitochondrial DNA. The work will be done at MRRC RAMS, which possesses the set of methods which allow determining structural and gene mutation in somatic cells. The Center is a leader in basic and clinical Radiobiology and Radiation Oncology.
Expected results will be used for clearing up correlation between epidemiological and molecular-genetic indicators for cancer risk.
MRRC RAMS is a supervisor and principle investigator of National programs related to minimization of health effects of the Chernobyl accident. The study of gene mutations in liquidators of the accident, who had received doses below 0.25 Gy is carried out there.
Role of foreign collaborators
Estimation of mutations in mitochondrial DNA in peripheral blood cells in exposed people will be made in Japan at the Department of molecular medicine of the institute of Atomic Disease, Medical school of Nagasaki University, Japan. Blood will be sampled, treated and aliquots will be sent to Japan. Nuclear DNA extracted from the same samples will be investigated at the MRRC RAMS. Exchange and comparison of information about detected mutations in nuclear and mitochondrial DNAs and data of cytogenetic analysis in relation to radiation dose and the age of subjects under study will be made.