TP53 codon 72 polymorphism in radiation-associated human papillary thyroid cancer.
The study investigated an association between the germline polymorphism at TP53 codon 72 and the development of papillary thyroid cancer (PTC) following exposure to radiation from the Chernobyl accident. TP53 genotype was examined in 48 pediatric/adolescent (age at diagnosis <18 years) and 68 adult post-Chernobyl patient with PTC, 53 adult patients with sporadic PTC and 313 healthy individuals from Russian-Ukrainian population. In addition, we evaluated loss of heterozygosity for TP53 and the allele expression ratio. The genotype of the patients was correlated with clinicopathological data. Arg TP53 homozygotes were found to be significantly underrepresented among adults with post-Chernobyl PTC, but not in children and adolescents when compared with sporadic PTC cases and the general population. In the tumors, cell transformation did not lead to allelic loss or biased TP53 allele expression in heterozygous individuals. None of TP53 genotypes specifically associated with tumor stage and morphology, however there were particular correlations with lymph node status in certain age groups of radiation-associated cases not seen in sporadic PTCs. The findings suggest TP53 allele combinations other than Arg/Arg may contribute to the risk of development of PTC in individuals exposed to radiation during their late childhood, adolescence or in young adulthood.
Rogounovitch
Tatiana I
TI
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
Saenko
Vladimir A
VA
Ashizawa
Kiyoto
K
Sedliarou
Ilya A
IA
Namba
Hiroyuki
H
Abrosimov
Aleksandr Yu
AY
Lushnikov
Eugeny F
EF
Roumiantsev
Pavel O
PO
Konova
Marina V
MV
Petoukhova
Natalia S
NS
Tchebotareva
Irina V
IV
Ivanov
Viktor K
VK
Chekin
Sergei Yu
SY
Bogdanova
Tatiana I
TI
Tronko
Mykola D
MD
Tsyb
Anatoly F
AF
Thomas
Gerry A
GA
Yamashita
Shunichi
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics / Q000528:radiation effects; D009367:Neoplasm Staging; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000473:pathology*; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D016159:Tumor Suppressor Protein p53