title: Are pre-miR-146a and PTTG1 associated with papillary thyroid cancer?
abstract: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. The predisposition to developing this carcinoma by the heterozygous state of rs2910164 within the precursor of the miR-146a has been reported, but recently not confirmed. Interestingly, on the same chromosome, almost 50 kb separate the pre-miR-146a from the pituitary tumor-transforming gene 1 (PTTG1), a proto-oncogene involved in several tumors, including thyroid cancers. In this study, we analyzed, using a case-control design, the genetic association between PTC and the genomic region encompassing pre-miR-146a rs2910164 and PTTG1 rs1862391 and rs2910202. We enrolled 307 affected patients and 206 healthy controls. The possible presence of thyroid nodules in controls was excluded by ultrasonography. All the cases were submitted to single-nucleotide polymorphism (SNP) genotyping of pre-miR-146a and PTTG1, and risk association analyses were carried out. The genotypic and allelic frequencies of pre-miR-146a rs2910164 were not statistically different in the patients and controls, and this SNP was not in linkage disequilibrium with the investigated PTTG1 SNPs. Consistently, meta-analyses, the first including all the affected cases published to date, did not confirm the previously reported association of the heterozygous CG genotype with PTC. The PTTG1 SNPs exhibited the same allelic frequency in the patients and controls and were not associated with the disease. In conclusion, in a well-selected Italian population, neither pre-miR-146a rs2910164 nor PTTG1 rs1862391 and rs2910202 were found to be associated with the risk of developing PTC.
authors.affiliation: Unit and Chair of Endocrinology and MetabolismNOCSAE, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Pietro Giardini 1355, 41126 Modena, Italy Center for Genomic ResearchUniversity of Modena and Reggio Emilia, Modena, Italy Department of Clinical Sciences and Community HealthUniversity of Milan, Milan, Italy Endocrine UnitFondazione IRCCS Ca' Granda Milan, Milan, Italy Azienda USL of ModenaModena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Marino
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirello
authors.forename: Valentina
authors.initials: V
authors.lastname: Gnarini
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
authors.forename: Elisa
authors.initials: E
authors.lastname: Pignatti
authors.forename: Livio
authors.initials: L
authors.lastname: Casarini
authors.forename: Chiara
authors.initials: C
authors.lastname: Diazzi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rochira
authors.forename: Katia
authors.initials: K
authors.lastname: Cioni
authors.forename: Bruno
authors.initials: B
authors.lastname: Madeo
authors.forename: Cesare
authors.initials: C
authors.lastname: Carani
authors.forename: Manuela
authors.initials: M
authors.lastname: Simoni
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
keywords: PTTG1; SNP; miRNA; papillary thyroid carcinoma; polymorphism; pre-mir-146a; rs1862391; rs2910164; rs2910202