ret/PTC activation is not associated with individual radiation dose estimates in a pilot study of neoplastic thyroid nodules arising in Russian children and adults exposed to Chernobyl fallout.
BACKGROUND
Ionizing radiation is the strongest risk factor known for the development of thyroid neoplasia. While previous studies have demonstrated a high prevalence of ret/papillary thyroid cancer (PTC) activation in cohorts of patients developing thyroid nodules after childhood exposure to ionizing radiation, no study has directly compared ret/PTC activation with individual estimates of radiation dose to the thyroid. This study combines individual thyroid dosimetry data with molecular analysis of surgically removed thyroid nodules in order to determine if ret/PTC activation in thyroid nodules is associated with increasing estimated radiation dose from Chernobyl.


METHODS
This pilot study included adults and children diagnosed with PTC (n = 76) and children diagnosed with follicular adenomas (n = 24) during May 1986 through December 1999, who were living in the Bryansk Oblast of the Russian Federation at the time of the Chernobyl accident, who had paraffin-embedded thyroid surgical samples available and for whom an individual dose to the thyroid could be estimated. The frequency of ret/PTC activation was determined using RT-PCR analysis. Individual radiation doses to the thyroid were estimated using a semiempirical model, and data were collected by detailed interview, primarily of the participant's mother.


RESULTS
ret/PTC oncogene activation was detected in 23.8% (5/21) and 14.5% (8/55) of the childhood and adult PTC cases, respectively, and 8.3% (2/24) of the follicular adenoma cases. No statistically significant differences were noted in age at the time of exposure or diagnosis, gender, latency period, or estimated radiation dose between PTC patients with or without ret/PTC activation. Further, no significant dose-response relationship was detected among PTC patients with ret/PTC activation.


CONCLUSIONS
Factors other than individual thyroid radiation doses may influence the development and subsequent detection of ret/PTC oncogene activation in radiation related PTC arising in the Bryansk Oblast of the Russian Federation in the aftermath of the Chernobyl accident.
Tuttle
R Michael
RM
Endocrinology Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. tuttlem@mskcc.org
Lukes
Yvonne
Y
Onstad
Lynn
L
Lushnikov
Eugeni
E
Abrosimov
Alexander
A
Troshin
Vladislav
V
Tsyb
Anatoli
A
Davis
Scott
S
Kopecky
Kenneth J
KJ
Francis
Gary
G
D000328:Adult; D047852:Chernobyl Nuclear Accident; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D010865:Pilot Projects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000503:physiopathology*; D016606:Thyroid Nodule / Q000503:physiopathology*; D014455:Ukraine
D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C093573:ret-PTC fusion oncoproteins, human