Molecular Epidemiology of Radiation-Associated Cancers

Several analytic efforts are underway in the U.S. Radiologic Technologist cohort involving nested case-control studies of breast, thyroid, and skin cancer as well as benign breast disease. In a study of several ATM missense mutations, an individual variant was associated with breast cancer risk, a result that was replicated in a large breast cancer case-control study conducted by DCEG in Poland. Another rare missense mutation was associated with a significant increased risk in the radiologic technologists but not in Poland. These associations were somewhat stronger in subjects under age 50..

Variation in the detection, signaling, and repair of DNA damage contributes to human cancer risk. DNA damage in multiple cancer cases and controls was quantified using the alkaline comet assay. Increased DNA damage, as measured by this assay, was most consistently associated with breast followed by another cancer, early-onset breast cancer (less than or equal to 35 years old) and thyroid cancer, and with decreased risk among the long-lived cancer-free group. Measuring DNA damage phenotype may contribute to the identification of susceptible sub-groups since it appeared that there was a continuum of endogenous DNA damage that was highest among cancer cases, less in controls, and suggestively lowest in long-lived individuals. Genes involved in apoptosis and DNA repair are both essential for maintaining genomic integrity, thus genetic variants in apoptosis and DNA repair may increase susceptibility to radiation carcinogenesis. We therefore evaluated potential modification of the relationship between ionizing radiation exposure and breast cancer risk by polymorphic apoptosis and DNA repair gene variants. We found that the dose-response relationship between cumulative personal diagnostic radiation and breast cancer risk was significantly modified by variants in WRN, BRCA1, PRKDC, and IL1A, after adjusting for occupational dose.

The opportunity exists for a post-doctoral fellow to examine thyroid cancer risk in relation to germline variation in over 1000 candidate genes encompassing numerous pathways related to carcinogenesis. In addition, analytic opportunities will be available for a pooled genetic study of thyroid cancer using existing data from several international groups collaborating on studying germline polymorphisms. A study of skin cancers (melanoma, basal cell, squamous cell) are planned for which biospecimens will be collected.

Research Training in Radiation Epidemiology