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Fission and radiation protection

Radiation Exposures at an Early Age: Impact of Genotype on Breast Cancer Risk – Genes and Breast Cancer

Breast cancer is the most common cancer and a leading cause of cancer deaths among women worldwide. Known risk factors for breast cancer include genetic susceptibility and exposure to ionising radiation. The GENE-RAD-RISK project focuses on the conduct of multinational studies of pre-menopausal breast cancer risk in a variety of populations. These cohorts are chosen based on a high prevalence of radiation exposure and/or high prevalence of known mutations in susceptibility genes.

Evaluating exposure and susceptibility

Image of a digital phantom for calculating radiation doses received to the site of the breast cancer from radiotherapy, Institut Gustave Roussy, (IGR), France © Institut Gustave Roussy, Villejuif, France
Image of a digital phantom for calculating radiation doses received to the site of the breast cancer from radiotherapy, Institut Gustave Roussy, (IGR), France
© Institut Gustave Roussy, Villejuif, France
The aim of the project is to examine the joint roles of low-dose radiation exposure and genetic susceptibility in studying the cause of breast cancer in young women. Because of the nature of the question being addressed, the current project is based on a multinational collaboration as studies in single countries lack sufficient statistical power. The consortium brings together a powerful team with a wide range of expertise. The Radiation Group of the International Agency for Research on Cancer has considerable experience in the coordination of multi-centre international studies in radiation epidemiology, while the leading investigators for each of the cohorts included in the study are all established researchers in the field of cancer epidemiology or genetics.

Multinational studies

The project involves the conduct of separate but complementary multinational studies of breast cancer within different populations. This includes patient groups who survived a first cancer diagnosed before the age of 35 and were exposed to medical radiation and other groups with a known or suspected genetic predisposition to breast cancer - such as BRCA1 and 2 mutation carriers. The radiation dose to the breast from therapeutic and diagnostic exposures will be estimated and statistical methods developed to analyse the data collected in the studies and to integrate and exploit the results. This will allow derivation of risk estimates and consequences for radiation protection.

The study findings will be published in scientific symposia and research journals. Specific publications will be prepared, targeted towards oncologists and radiotherapists, in order to inform them of the results and assist them in implementing measures to reduce the risk of radio-induced breast cancer.

Identification of populations at a higher risk of cancer following irradiation

The project addresses specific issues of low-dose risks and identification of genes conferring predisposition to radiation-induced health effects. It will enhance our understanding of how ionising radiation influences the risk of breast cancer following exposure in childhood, adolescence and the early reproductive years, and will improve our understanding of mechanisms of cancer induction in general, particularly in relation to geneenvironment interactions. It will also assist in the identification of individuals who, because of a genetic alteration, have a potentially greater risk of radiationinduced cancer.

The subjects who participate in the project will not benefit directly from the results of this study. However, it is expected that breast cancer management in different populations (populations with high-dose environmental radiation exposure following nuclear accidents, patients treated for a first cancer and cohorts of BRCA1/2 mutation carriers) may be improved by the results. Moreover, the results will help to predict responses to radiotherapy and to identify high-risk populations among patients for whom cancer therapy needs to be tailored to take into account their inherent susceptibility to radiation-induced cancer.

Modified methodologies to reduce risk

Through the identification of susceptible groups, and the study of factors that may modify the effects of radiation exposure, the project has implications for assessing the adequacy and generalisation of current national and international radiation protection guidelines and recommendations. In the case of identifying susceptible groups, plans will be made with appropriate experts for disseminating risk information to relevant population groups, together with wider publicity on the project outcomes.

If specific interactions are found, and a higher risk of radiation-induced breast cancer risk is observed in populations with particular polymorphisms, screening or counselling can be adapted and breast cancer screening protocols (and possibly treatment) can be modified. In particular, diagnostic radiation exposures (mammography) for these populations may need to be restricted and therapeutic protocols, in the case of malignancies, adapted. As such this will also contribute to the debate about long-term risk of new radiotherapy techniques, such as Conformational Radiotherapy and Intensity Modulated Radiotherapy Treatment, as well as to the evaluation of the risk/benefit assessment of radiation therapy versus novel targeted chemotherapy agents.

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