title: CCND1gene polymorphic variants in patients with differentiated thyroid carcinoma.
abstract: Alterations in theCCND1gene affect the cell cycle and are frequently observed in a variety of cancers. While the most frequent mutations that occur in thyroid tumor tissue have been characterized, the genetic factors that predispose individuals to differentiated thyroid cancer (DTC) remain to be elucidated. The present study examined whether theCCND1c.723G>A (rs9344; p.Pro241=) and c.669C>T (rs3862792; p.Phe223=) variants have an impact on DTC susceptibility. A cohort consisting of 652 patients diagnosed with DTC were analyzed and comapred with a reference group of 799 subjects from the general population. Pyrosequencing was used as the genotyping technique. In order to determine the statistical significance of differences observed in the genotypic and allelic frequencies between the compared groups, GraphPad Prism 4 was used. At the rs9344 locus in the DTC patients, a higher frequency of allele A [P=0.032; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.014-1.361] and the AA homozygous genotype (P=0.028; OR, 1.41; 95% CI, 1.059-1.989) was observed compared with the control population group. The differences were stronger for papillary carcinomas (OR 1.45; 95% CI, 1.059-1.989), but were not significant in follicular tumors. No statistically significant differences were noted in the frequency of genotypes or alleles at the rs3862792 locus in the examined groups. The present findings indicate that the c.723A variant of theCCDN1gene may be a susceptibility low penetrance allele in the development of papillary thyroid cancer in the population studied, however it does not impact on multifocality, metastatic ability or age at diagnosis. A cumulative effect of the analyzedCCND1gene variants was also excluded.
authors.affiliation: NanoBioMedical Center, Adam Mickiewicz University, Poznań 61-614, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Hryhorowicz
authors.affiliation: Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Ziemnicka
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kaczmarek-Ryś
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Hoppe-Gołębiewska
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pławski
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Skrzypczak-Zielińska
authors.affiliation: Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szkudlarek
authors.affiliation: Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Gołąb
authors.affiliation: Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Poland.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Budny
authors.affiliation: Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Ruchała
authors.affiliation: NanoBioMedical Center, Adam Mickiewicz University, Poznań 61-614, Poland ; Institute of Human Genetics, Polish Academy of Sciences, Poznań 60-479, Poland ; Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań 60-632, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Słomski
keywords: CCND1 gene; cancer susceptibility alleles with low penetrance; differentiated thyroid carcinoma; papillary thyroid carcinoma