title: Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas.
abstract: A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to (131)iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The 'Genrisk-T' cohort consisted of 45 PTCs and the 'UkrAm' cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation.
authors.affiliation: Research Unit Radiation Cytogenetics and.
authors.forename: Martin
authors.initials: M
authors.lastname: Selmansberger
authors.affiliation: Institute of Radiation Protection, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85674 Neuherberg, Germany, christian.kaiser@helmholtz-muenchen.de.
authors.forename: Jan Christian
authors.initials: JC
authors.lastname: Kaiser
authors.affiliation: Research Unit Radiation Cytogenetics and.
authors.forename: Julia
authors.initials: J
authors.lastname: Hess
authors.affiliation: Institute of Radiation Protection, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85674 Neuherberg, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Güthlin
authors.affiliation: Radiation Protection Institute, Ukrainian Academy of Technological Sciences, 04050 Kyiv, Ukraine.
authors.forename: I
authors.initials: I
authors.lastname: Likhtarev
authors.affiliation: Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of the Ukraine, 254114 Kyiv, Ukraine.
authors.forename: Victor
authors.initials: V
authors.lastname: Shpak
authors.affiliation: Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of the Ukraine, 254114 Kyiv, Ukraine.
authors.forename: Mykola
authors.initials: M
authors.lastname: Tronko
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MD 20892, USA.
authors.forename: Alina
authors.initials: A
authors.lastname: Brenner
authors.affiliation: Bundeswehr Institute of Radiobiology, 80937 Munich, Germany and.
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
authors.affiliation: Institut für Medizinische Biometrie, Epidemiologie und Informatik (IMBEI), Johannes Gutenberg Universität, 55131 Mainz, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Blettner
authors.affiliation: Research Unit Radiation Cytogenetics and.
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.affiliation: Institute of Radiation Protection, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85674 Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Jacob
authors.affiliation: Research Unit Radiation Cytogenetics and.
authors.forename: Horst
authors.initials: H
authors.lastname: Zitzelsberger
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D002291:Carcinoma, Papillary; D047852:Chernobyl Nuclear Accident; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D016015:Logistic Models; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism / Q000601:surgery; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D008869:Microtubule-Associated Proteins; C109878:cytoplasmic linker protein 115