BRCA mutations in women from Belarus exposed to radiation from Chernobyl compared to controls

Full text: There are several reports of studies that suggest a causal association between exposure to ionizing radiation and the subsequent development of breast cancer. Since the Chernobyl accident in 1986, there has been a dramatic increase in thyroid cancer after radiation exposure, especially among those who were exposed as young children and living in the areas with the greatest contamination. One early report found that women exposed to radiation from Chernobyl had a slight, but significant increase in the incidence of breast cancer. No other data are reported about additional risks for the development of breast cancer in this population. With funding from a NIH R03 grant application and the Child Health International Foundation, we are investigating the molecular epidemiology of breast cancer in Belarusian women exposed at ages < 40 years to high radiation doses from the Chernobyl accident compared to controls for the common Eastern European BRCA 1/2 mutations. As occurred 20+ years after exposure of Japanese women exposed to radiation fallout from atomic bombs in 1945, we expect to find a sustained increase in breast cancer for the coming decade and longer. We accomplished nearly all of the following objectives in the evaluation of Belarusian women with breast cancer and controls who were exposed to sustained high doses of ionizing radiation in 1986. When our US collaborators visited the Republic of Belarus, they (a) met with Belarusian consultants, co-investigators, other health care professionals and administrators and developed a formal collaboration to study breast cancer, BRCA mutations and radiation exposure; (b) recruited Belarusian cancer epidemiologists, Chernobyl radiation dosimetrists, and cancer registry/database management personnel; (c) began a collaboration with the Director of Breast Cancer Surgery for the Republic of Belarus and met several breast cancer specialists in surgery and oncology under his direction; and (d) met medical directors of the regions where control and radiation-exposed populations were later recruited into the study. Recruitment is complete, the data base is established, informed consents processed, and specimens collected for molecular analysis. Jointly we discussed the clinical and laboratory facilities that are utilized for the molecular studies at the International Sakharov Environmental University in Minsk and laboratories in the Department of Pathology in Gomel. We established collaborative agreements with medical, administrative and governmental organizations for implementation and continuation of the research pilot study; have organized the fiscal collaboration with the Belarus Committee Children of Chernobyl NGO at their office in Minsk; have established their acceptance by our collaborating organizations; and developed and implemented the instruments for data acquisition and storage, interview questionnaires in Russia and/or Belarus with accuracy of content confirmation through back translation by another group of translators and created questionnaires from currently NIH-funded studies as models for this study. We established the mechanism and implemented the collection of dried blood spotted filter paper specimens and blood collection in anticoagulant containing tubes for DNA extraction and storage in Minsk where the BRCA screening are performed. We are completing the analysis of the DNA extracted from these specimens for common BRCA1 and 2 mutations, and are comparing these findings with histology, biochemical markers and molecular data from breast cancer tissue. After specimens are tested and data analyzed for this research study, we shall continue these methods to screen large populations of women exposed to high radiation doses and controls for the common BRCA mutations. We are preparing the submission of our larger proposed study to an international donor organization and to the NIH/NCI as a R01 research grant application. (authors)