BACKGROUND: Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. METHODS: Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of (131) I to the thyroid. Associations between mutation types and (131) I dose and other characteristics were explored. RESULTS: RET/PTC (ret proto-oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement were identified. A significant negative association with (131) I dose for BRAF and RAS point mutations and a significant concave association with (131) I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine-deficient Zhytomyr region, younger age at exposure or surgery, and male sex. CONCLUSIONS: These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with (131) I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and (131) I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients.
BACKGROUND: Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. METHODS: Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of (131) I to the thyroid. Associations between mutation types and (131) I dose and other characteristics were explored. RESULTS:RET/PTC (ret proto-oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement were identified. A significant negative association with (131) I dose for BRAF and RAS point mutations and a significant concave association with (131) I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine-deficient Zhytomyr region, younger age at exposure or surgery, and male sex. CONCLUSIONS: These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with (131) I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and (131) I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients.
Authors: Emanuela Roccato; Paola Bressan; Guido Sabatella; Cristiano Rumio; Laura Vizzotto; Marco A Pierotti; Angela Greco Journal: Cancer Res Date: 2005-04-01 Impact factor: 12.701
Authors: H M Rabes; E P Demidchik; J D Sidorow; E Lengfelder; C Beimfohr; D Hoelzel; S Klugbauer Journal: Clin Cancer Res Date: 2000-03 Impact factor: 12.531
Authors: Edna T Kimura; Marina N Nikiforova; Zhaowen Zhu; Jeffrey A Knauf; Yuri E Nikiforov; James A Fagin Journal: Cancer Res Date: 2003-04-01 Impact factor: 12.701
Authors: Marina N Nikiforova; Paul W Biddinger; Christy M Caudill; Todd G Kroll; Yuri E Nikiforov Journal: Am J Surg Pathol Date: 2002-08 Impact factor: 6.394
Authors: Scott Davis; Valery Stepanenko; Nikolai Rivkind; Kenneth J Kopecky; Paul Voillequé; Vladimir Shakhtarin; Evgeni Parshkov; Sergei Kulikov; Evgeni Lushnikov; Alexander Abrosimov; Vladislav Troshin; Galina Romanova; Vladimir Doroschenko; Anatoli Proshin; Anatoly Tsyb Journal: Radiat Res Date: 2004-09 Impact factor: 2.841
Authors: Valentin A Stezhko; Elena E Buglova; Larissa I Danilova; Valentina M Drozd; Nikolaj A Krysenko; Nadia R Lesnikova; Victor F Minenko; Vladislav A Ostapenko; Sergey V Petrenko; Olga N Polyanskaya; Valery A Rzheutski; Mykola D Tronko; Olga O Bobylyova; Tetyana I Bogdanova; Ovsiy V Ephstein; Iryna A Kairo; Olexander V Kostin; Ilya A Likhtarev; Valentin V Markov; Valery A Oliynik; Viktor M Shpak; Valeriy P Tereshchenko; Galina A Zamotayeva; Gilbert W Beebe; Andre C Bouville; Aaron B Brill; John D Burch; Daniel J Fink; Ellen Greenebaum; Geoffrey R Howe; Nickolas K Luckyanov; Ihor J Masnyk; Robert J McConnell; Jacob Robbins; Terry L Thomas; Paul G Voillequé; Lydia B Zablotska Journal: Radiat Res Date: 2004-04 Impact factor: 2.841
Authors: Jonathan M Samet; Amy Berrington de González; Lawrence T Dauer; Maureen Hatch; Ourania Kosti; Fred A Mettler; Merriline M Satyamitra Journal: Radiat Res Date: 2017-11-14 Impact factor: 2.841
Authors: Rebecca J Leeman-Neill; Lindsey M Kelly; Pengyuan Liu; Alina V Brenner; Mark P Little; Tetiana I Bogdanova; Viktoria N Evdokimova; Maureen Hatch; Liudmyla Y Zurnadzy; Marina N Nikiforova; Ning J Yue; Miao Zhang; Kiyohiko Mabuchi; Mykola D Tronko; Yuri E Nikiforov Journal: Cancer Date: 2013-12-10 Impact factor: 6.860
Authors: Bálint Tobiás; Csaba Halászlaki; Bernadett Balla; János P Kósa; Kristóf Árvai; Péter Horváth; István Takács; Zsolt Nagy; Evelin Horváth; János Horányi; Balázs Járay; Eszter Székely; Tamás Székely; Gabriella Győri; Zsuzsanna Putz; Magdolna Dank; Zsuzsanna Valkusz; Béla Vasas; Béla Iványi; Péter Lakatos Journal: Pathol Oncol Res Date: 2015-08-11 Impact factor: 3.201