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Radiation exposures at an early age: impact of genotype on breast cancer risk

Final Report Summary - GENE-RAD RISK (Radiation exposures at an early age: Impact of genotype on breast cancer risk)

Breast cancer is the most common cancer and a leading cause of cancer death for women worldwide. Among the known risk factors for breast cancer are genetic susceptibility and exposure to ionising radiation.

The GENE-RAD-RISK project focussed on the conduct of multinational studies of pre-menopausal breast cancer risk in different populations, chosen on the basis of high prevalence of radiation exposure and high prevalence of known mutations in susceptibility genes. The overall objective of the project was to conduct an epidemiological study, designed to examine the role of radiation exposure in the aetiology of breast cancer in young women and study its possible interaction with genetic susceptibility in the BRCA1 and BRCA2 mutation cohort. A supplementary objective was to study the possible modifying effects of other risk factors, including therapies other than radiation.

Overall, nearly 2000 cases of breast cancer, as well as their matched controls and unaffected mutation carriers from four European countries were included in the studies. The consortium brought together a powerful team, including epidemiologists, radiation oncologists and physicists, dosimetrists, molecular biologists and statisticians. The obtained results not only contributed to the understanding of the mechanisms of carcinogenesis, but also had important public health implications for the protection of patients treated with radiotherapy.

The project was structured in five distinct, yet interrelated, work packages, which undertook the following activities:
1. case control studies in populations with medical radiation exposures;
2. cohort study of populations of BRCA1 and BRCA2 mutation carriers;
3. dose reconstruction;
4. statistical analyses, risk estimates and consequences for radiation protection;
5. consortium management and coordination.

Core protocols for case control studies were developed, along with a questionnaire aiming to establish a set of questions related to potential risk factors for breast cancer. Standard forms were established to abstract information from medical records in different countries, as well as databases to enter such information for further processing. In addition, special software was developed to process the collected data and calculate individual radiotherapy doses. Uncertainty in the data was evaluated and taken into account during this process. A cumulative breast dose score as an approximation of organ dose from radiodiagnostic procedures was also calculated. Furthermore, analyses of the relation between radiation dose and breast cancer risk in three sub-populations were conducted.

In addition to the project activities, biological samples were collected to allow for further gene analyses, for which funding would be sought after the project completion. Moreover, methods for analysing epidemiological data were developed to be applied in future analyses of gene radiation interactions.