<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ruiz-Llorente, S.</style></author><author><style face="normal" font="default" size="100%">Montero-Conde, C.</style></author><author><style face="normal" font="default" size="100%">Milne, R. L.</style></author><author><style face="normal" font="default" size="100%">Moya, C. M.</style></author><author><style face="normal" font="default" size="100%">Cebrian, A.</style></author><author><style face="normal" font="default" size="100%">Leton, R.</style></author><author><style face="normal" font="default" size="100%">Cascon, A.</style></author><author><style face="normal" font="default" size="100%">Mercadillo, F.</style></author><author><style face="normal" font="default" size="100%">Landa, I.</style></author><author><style face="normal" font="default" size="100%">Borrego, S.</style></author><author><style face="normal" font="default" size="100%">Perez de Nanclares, G.</style></author><author><style face="normal" font="default" size="100%">Alvarez-Escola, C.</style></author><author><style face="normal" font="default" size="100%">Diaz-Perez, J. A.</style></author><author><style face="normal" font="default" size="100%">Carracedo, A.</style></author><author><style face="normal" font="default" size="100%">Urioste, M.</style></author><author><style face="normal" font="default" size="100%">Gonzalez-Neira, A.</style></author><author><style face="normal" font="default" size="100%">Benitez, J.</style></author><author><style face="normal" font="default" size="100%">Santisteban, P.</style></author><author><style face="normal" font="default" size="100%">Dopazo, J.</style></author><author><style face="normal" font="default" size="100%">Ponder, B. A.</style></author><author><style face="normal" font="default" size="100%">M. Robledo</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Association study of 69 genes in the ret pathway identifies low-penetrance loci in sporadic medullary thyroid carcinoma</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Res</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">80 and over Carcinoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Adolescent Adult Aged Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Proto-Oncogene Proteins c-ret/*genetics/metabolism Signal Transduction Thyroid Neoplasms/*genetics/metabolism Transcription</style></keyword><keyword><style  face="normal" font="default" size="100%">Medullary/*genetics/metabolism Case-Control Studies Cyclin-Dependent Kinase Inhibitor p15/biosynthesis/genetics Female Genetic Predisposition to Disease Germ-Line Mutation Haplotypes Humans Male Middle Aged Penetrance Polymorphism</style></keyword><keyword><style  face="normal" font="default" size="100%">Single Nucleotide Promoter Regions</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2007</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=17909067</style></url></web-urls></urls><number><style face="normal" font="default" size="100%">19</style></number><volume><style face="normal" font="default" size="100%">67</style></volume><pages><style face="normal" font="default" size="100%">9561-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">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.</style></abstract><notes><style face="normal" font="default" size="100%">Ruiz-Llorente, Sergio Montero-Conde, Cristina Milne, Roger L Moya, Christian M Cebrian, Arancha Leton, Rocio Cascon, Alberto Mercadillo, Fatima Landa, Inigo Borrego, Salud Perez de Nanclares, Guiomar Alvarez-Escola, Cristina Diaz-Perez, Jose Angel Carracedo, Angel Urioste, Miguel Gonzalez-Neira, Anna Benitez, Javier Santisteban, Pilar Dopazo, Joaquin Ponder, Bruce A Robledo, Mercedes Medullary Thyroid Carcinoma Clinical Group Research Support, Non-U.S. Gov’t United States Cancer research Cancer Res. 2007 Oct 1;67(19):9561-7.</style></notes></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Milne, R. L.</style></author><author><style face="normal" font="default" size="100%">Ribas, G.</style></author><author><style face="normal" font="default" size="100%">Gonzalez-Neira, A.</style></author><author><style face="normal" font="default" size="100%">Fagerholm, R.</style></author><author><style face="normal" font="default" size="100%">Salas, A.</style></author><author><style face="normal" font="default" size="100%">Gonzalez, E.</style></author><author><style face="normal" font="default" size="100%">Dopazo, J.</style></author><author><style face="normal" font="default" size="100%">Nevanlinna, H.</style></author><author><style face="normal" font="default" size="100%">M. Robledo</style></author><author><style face="normal" font="default" size="100%">Benitez, J.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">ERCC4 associated with breast cancer risk: a two-stage case-control study using high-throughput genotyping</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Res</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">80 and over Breast Neoplasms/epidemiology/*genetics/pathology Case-Control Studies DNA-Binding Proteins/genetics/*physiology Female Finland/epidemiology Genes</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult Aged Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Recessive Genetic Predisposition to Disease Genotype Humans Introns/genetics Linkage Disequilibrium Middle Aged Neoplasm Proteins/genetics/*physiology Neoplasm Staging *Polymorphism</style></keyword><keyword><style  face="normal" font="default" size="100%">Single Nucleotide Risk Spain/epidemiology</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2006</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=17018596</style></url></web-urls></urls><number><style face="normal" font="default" size="100%">19</style></number><volume><style face="normal" font="default" size="100%">66</style></volume><pages><style face="normal" font="default" size="100%">9420-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The failure of linkage studies to identify further high-penetrance susceptibility genes for breast cancer points to a polygenic model, with more common variants having modest effects on risk, as the most likely candidate. We have carried out a two-stage case-control study in two European populations to identify low-penetrance genes for breast cancer using high-throughput genotyping. Single-nucleotide polymorphisms (SNPs) were selected across preselected cancer-related genes, choosing tagSNPs and functional variants where possible. In stage 1, genotype frequencies for 640 SNPs in 111 genes were compared between 864 breast cancer cases and 845 controls from the Spanish population. In stage 2, candidate SNPs identified in stage 1 (nominal P &lt; 0.01) were tested in a Finnish series of 884 cases and 1,104 controls. Of the 10 candidate SNPs in seven genes identified in stage 1, one (rs744154) on intron 1 of ERCC4, a gene belonging to the nucleotide excision repair pathway, was associated with recessive protection from breast cancer after adjustment for multiple testing in stage 2 (odds ratio, 0.57; Bonferroni-adjusted P = 0.04). After considering potential functional SNPs in the region of high linkage disequilibrium that extends across the entire gene and upstream into the promoter region, we concluded that rs744154 itself could be causal. Although intronic, it is located on the first intron, in a region that is highly conserved across species, and could therefore be functionally important. This study suggests that common intronic variation in ERCC4 is associated with protection from breast cancer.</style></abstract><notes><style face="normal" font="default" size="100%">Milne, Roger Laughlin Ribas, Gloria Gonzalez-Neira, Anna Fagerholm, Rainer Salas, Antonio Gonzalez, Emilio Dopazo, Joaquin Nevanlinna, Heli Robledo, Mercedes Benitez, Javier Comparative Study Multicenter Study Research Support, Non-U.S. Gov’t United States Cancer research Cancer Res. 2006 Oct 1;66(19):9420-7.</style></notes></record></records></xml>