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oai:repisalud.isciii.es:20.500.12105/272122026-02-07T01:19:46Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571

00925njm 22002777a 4500 dc Montero-Conde, Cristina author Ruiz-Llorente, Sergio author Montero-Conde, Cristina author Milne, Roger L author Moya, Christian M author Cebrián, Arancha author Letón, Rocío author Cascón, Alberto author Mercadillo, Fátima author Landa, Iñigo author Borrego, Salud author Pérez de Nanclares, Guiomar author Alvarez-Escolá, Cristina author Díaz-Pérez, José Angel author Carracedo, Angel author Urioste, Miguel author González-Neira, Anna author Benítez, Javier author Santisteban, Pilar author Dopazo, Joaquín author Ponder, Bruce A author Robledo Batanero, Mercedes author 2007-10-01 To date, few association studies have been done to better understand the genetic basis for the development of sporadic medullary thyroid carcinoma (sMTC). To identify additional low-penetrance genes, we have done a two-stage case-control study in two European populations using high-throughput genotyping. We selected 417 single nucleotide polymorphisms (SNP) belonging to 69 genes either related to RET signaling pathway/functions or involved in key processes for cancer development. TagSNPs and functional variants were included where possible. These SNPs were initially studied in the largest known series of sMTC cases (n = 266) and controls (n = 422), all of Spanish origin. In stage II, an independent British series of 155 sMTC patients and 531 controls was included to validate the previous results. Associations were assessed by an exhaustive analysis of individual SNPs but also considering gene- and linkage disequilibrium-based haplotypes. This strategy allowed us to identify seven low-penetrance genes, six of them (STAT1, AURKA, BCL2, CDKN2B, CDK6, and COMT) consistently associated with sMTC risk in the two case-control series and a seventh (HRAS) with individual SNPs and haplotypes associated with sMTC in the Spanish data set. The potential role of CDKN2B was confirmed by a functional assay showing a role of a SNP (rs7044859) in the promoter region in altering the binding of the transcription factor HNF1. These results highlight the utility of association studies using homogeneous series of cases for better understanding complex diseases. Cancer Res . 2007 Oct 1;67(19):9561-7. Cancer Research 17909067 https://hdl.handle.net/20.500.12105/27212 SINGLE-NUCLEOTIDE POLYMORPHISMS SUSCEPTIBILITY GENE SIGNALING PATHWAY HUMAN GENOME KAPPA-B CANCER PROTOONCOGENE RECRUITMENT METHYLATION P16(INK4A) Association study of 69 genes in the ret pathway identifies low-penetrance loci in sporadic medullary thyroid carcinoma.