TP53, ATM and HDM2 SNP profiling in radiation-related human thyroid cancer

Abstract

Thyroid gland is an organ particularly vulnerable to radiation as known from previous studies that investigated relationship between thyroid neoplastic disorders and radiation exposure in man. In particular, there is an evidence of increased risk of papillary thyroid cancer (PTC) in the individuals exposed to ionizing radiation especially if exposure had taken place at the young age. In spite of extensive investigations, specific molecular events underlying radiation-related carcinogenesis are not fully understood. Mutation patterns of the oncogenes implicated in thyroid carcinogenesis (ret/PTC and TRK rearrangements, BRAF, RAS, Gsa) or TP53 tumor suppressor gene have not proved a distinctive molecular signature that may unambiguously be associated with radiation-induced thyroid tumors.An alternative approach to elucidation of the basics of thyroid cancer development in radiation victims may be the identification of individual genetic characteristics of the patients with radiation-associated PTCs. In our work, we have profiled a set of SNPs in several genes whose products are involved in the DNA damage pathway, TP53, ATM and HDM2. As a result, several SNPs displaying a significant association with radiation-related or sporadic adult or childhood PTC have been detected. These findings demonstrate that molecular epidemiology studies hold a promise in the problem of detection of the genetic traits potentially contributing to or modifying the susceptibility to radiation-induced thyroid carcinogenesis in humans.