Sixty years of follow-up of Hiroshima and Nagasaki survivors: Current progress in molecular epidemiology studies

Title: Sixty years of follow-up of Hiroshima and Nagasaki survivors: Current progress in molecular epidemiology studies
Author: Nakachi, Kei / Hayashi, Tomonori / Hamatani, Kiyohiro / Eguchi, Hidetaka / Kusunoki, Yoichiro

Reference: Mutation Research/Reviews in Mutation Research, 659 (1-2), p.109-117, Jul 2008
doi: 10.1016/j.mrrev.2008.02.001

Keywords: Radiation; Atomic-bomb survivors; Somatic mutation; Oxidative stress; Colorectal carcinogenesis; Microsatellite instability; Thyroid carcinogenesis

Abstract: This article provides an overview of the on-going molecular epidemiology studies among atomic-bomb survivors conducted at the Radiation Effects Research Foundation in Japan. The focus is on: (a) inter-individual variations in sensitivity to radiation-induced somatic mutations (glycophorin A (GPA) mutations) and their potential relevance to differences in susceptibility to radiation-related cancers and (b) the role of specific mutations/rearrangements in radiation-induced thyroid and colorectal cancers. The glycophorin A mutant fractions showed large differences between the survivors at each of the estimated bone marrow doses. Of note is the finding at doses ≥1 Gy; that the slope of the mutant fraction was significantly higher in the ‘cancer group’ than in the ‘non-cancer group’. This study provided the basis for validating the use of γH2AX and reticulocyte micronucleus assays for evaluating radiosensitivity differences and genetic instability, respectively, in our studies in the coming years. Preliminary results from our molecular oncology studies on adult-onset papillary thyroid cancer provide evidence for the induction of RET/PTC rearrangements and BRAF point mutation (both known to be early stage events in adult-onset papillary thyroid cancer) but with a difference: cases associated with the rearrangements were more frequent at high doses, and developed sooner than those with BRAF mutation. In the case of colorectal cancer, the results suggest that radiation exposure might influence microsatellite instability (MSI) status through MSI-related epigenetic and genetic alterations—processes that might occur in the early stage of colorectal carcinogenesis.

…spontaneous thyroid cancer in the Japanese…variant papillary thyroid cancer was not found in…although this cancer has been frequently…observed among post-Chernobyl children. A major…event in papillary thyroid carcinogenesis is…

URL: http://www.sciencedirect.com/science/article/pii/S1383574208000318

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