Abstract 2544: Associations between RET/PTC rearrangements, BRAF and RAS mutations and radiation dose, age at exposure, and latency in post-Chernobyl thyroid cancer

Abstract

Abstract Introduction: Childhood exposure to I-131 from the Chernobyl accident was associated with a dramatic increase in incidence of papillary thyroid cancer (PTC). PTCs are characterized by several genetic alterations including RET/PTC rearrangements and point mutations of BRAF and RAS. Association between mutations and radiation doses has not been studied in post-Chernobyl tumors. Design: We analyzed 70 PTCs diagnosed in a Ukrainian-American cohort who were < 18 y.o. at the time of Chernobyl and received 0.008-8.6 Gy of I-131 to the thyroid. Thyroid doses were estimated based on radioactivity measurements taken shortly after the accident, environmental transport models, and interview data. BRAF and RAS mutations were identified by melting curve analysis and RET/PTC1 and RET/PTC3 by real-time RT-PCR. All mutations were confirmed by sequencing. Results: Identified mutations and patient characteristics are shown in Table 1. Logistic regression analysis demonstrated a significant decrease in I-131 dose for both BRAF and RAS mutations (p=0.005 and 0.026). There were highly statistically significant (p<0.001) differences between the trends with dose for BRAF and RAS vs RET/PTC. Comparing with BRAF and RAS mutations, the age at exposure was lower in cases with RET/PTC (p=0.001). RET/PTC3 was associated with a shorter latency period as compared to other mutations (p<0.02). Table 1. Genetic alterations and corresponding patient characteristics Conclusions: Our results demonstrate for the first time that prevalence of BRAF or RAS point mutations in post-Chernobyl tumors significantly decreases with increasing radiation dose, in contrast to the lack of decrease for RET/PTC. RET/PTC rearrangements are associated with younger age at exposure than point mutations of BRAF and RAS. These data provide support for the potential relationship between chromosomal rearrangements, but not point mutations, and radiation exposure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2544. doi:1538-7445.AM2012-2544