The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose.

Abstract

In papillary thyroid carcinogenesis, the constitutively activated mitogen-activated protein (MAP) kinase signaling pathway caused by a genetic alteration such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be a major early event. Among these, the recently identified BRAF(V600E) mutation has been found at high frequency in adult patients with papillary thyroid carcinoma (PTC). However, the association between this mutation and radiation exposure in adult PTC is still unknown. In this study, we examined the BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima, Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation with clinico-pathological and epidemiological variables. The median radiation dose in PTCs with the BRAF(V600E) mutation was significantly lower than that without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A significant difference was found in the median latency period (years elapsed from atomic bombing to diagnosis) between exposed patients with and without BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These findings were further confirmed by logistic regression analysis with BRAF(V600E) mutation status as a dependent variable and taking into account possible interactions between the variables. We found that the log-transformed radiation dose and latency period were independently associated with the BRAF(V600E) mutation (P=0.039 and P=0.010, respectively). These results suggest that involvement of BRAF mutation in thyroid carcinogenesis in exposed people may differ from that in the nonexposed people.

• Authors: Keiko Takahashi, Hidetaka Eguchi, Koji Arihiro, Reiko Ito, Kojiro Koyama, Midori Soda, John Cologne, Yuzo Hayashi, Yoshihiro Nakata, Kei Nakachi, Kiyohiro Hamatani
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 46 Issue 3 Pg. 242-8 (Mar 2007) ISSN: 0899-1987 [Print] United States
• PMID: 17186541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2006 Wiley-Liss, Inc.

Chemical References

• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Papillary (epidemiology, genetics)
• DNA Mutational Analysis
• Female
• Humans
• Japan (epidemiology)
• Male
• Middle Aged
• Neoplasms, Radiation-Induced (epidemiology, genetics)
• Nuclear Warfare (statistics & numerical data)
• Point Mutation (genetics)
• Proto-Oncogene Proteins B-raf (genetics)
• Radiation Dosage
• Survivors (statistics & numerical data)
• Thyroid Neoplasms (epidemiology, genetics)