RET/PTC and PAX8/PPARγ chromosomal rearrangements in post‐Chernobyl thyroid cancer and their association with iodine‐131 radiation dose and other characteristics1. Issue 10 (21st February 2013)

• Record Type: Journal Article
• Authors: Leeman‐Neill, Rebecca J.; Brenner, Alina V.; Little, Mark P.; Bogdanova, Tetiana I.; Hatch, Maureen; Zurnadzy, Liudmyla Y.; Mabuchi, Kiyohiko; Tronko, Mykola D.; Nikiforov, Yuri E.
• Is Part Of: Cancer. Volume 119:Issue 10(2013)
• Page Start: 1792
• Page End: 1799
• Publication Date: 2013-02-21
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.27893
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>BACKGROUND:</title> <p>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.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>METHODS:</title> <p>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 <sup>131</sup>I to the thyroid. Associations between mutation types and <sup>131</sup>I dose and other characteristics were explored.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>RESULTS:</title> <p> <italic>RET/PTC</italic> (ret proto‐oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by <italic>BRAF</italic> (15%) and <italic>RAS</italic> (8%) point mutations. Two tumors carrying <italic>PAX8/PPAR</italic>γ (paired box 8/peroxisome proliferator‐activated receptor gamma) rearrangement were identified. A significant negative association with <sup>131</sup>I dose for <italic>BRAF</italic> and <italic>RAS</italic> point mutations and a significant concave association with <sup>131</sup>I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear‐quadratic model for <italic>RET/PTC</italic> and <italic>PAX8/PPAR</italic>γ 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.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>CONCLUSIONS:</title> <p>These results provide the first demonstration of <italic>PAX8/PPAR</italic>γ rearrangements in post‐Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with <sup>131</sup>I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and <sup>131</sup>I exposure and point to a possible role of iodine deficiency in generation of <italic>RET/PTC</italic> rearrangements in these patients. Cancer 2013. © 2013 American Cancer Society.</p> </sec> </abstract>