Polymorphisms in selected DNA repair genes and cell cycle regulating genes involved in the risk of papillary thyroid carcinoma.
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed.


METHODS
Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTC patients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed.


RESULTS
XRCC1 T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics.


CONCLUSIONS
It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics.
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.|Department of Biochemistry, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Tereza
T
Halkova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
Sarka
S
Dvorakova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
Vlasta
V
Sykorova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
Eliska
E
Vaclavikova
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
Josef
J
Vcelak
Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic.
Petr
P
Vlcek
Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic.
Pavla
P
Sykorova
Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic.
Daniela
D
Kodetova
Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic.
Jan
J
Betka
Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic.
Petr
P
Lastuvka
Department of Surgery, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic.
Petr
P
Bavor
Department of Surgery, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic.
Jiri
J
Hoch
Department of ENT, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.
Rami
R
Katra
Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
Bela
B
Bendlova
D000328:Adult; D000483:Alleles; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
DNA repair; Papillary thyroid cancer; SNP; cell cycle regulator; molecular genetics