Location of Repository

Polymorphisms in CTNNBL1 in relation to colorectal cancer with evolutionary implications

By Stefanie Huhn, Dierk Ingelfinger, Justo Lorenzo Bermejo, Melanie Bevier, Barbara Pardini, Alessio Naccarati, Verena Steinke, Nils Rahner, Elke Holinski-Feder, Monika Morak, Hans K Schackert, Heike Görgens, Christian P Pox, Timm Goecke, Matthias Kloor, Markus Loeffler, Reinhard Büttner, Ludmila Vodickova, Jan Novotny, Kubilay Demir, Cristina-Maria Cruciat, Rebecca Renneberg, Wolfgang Huber, Christof Niehrs, Michael Boutros, Peter Propping, Pavel Vodička, Kari Hemminki and Asta Försti

Abstract

Colorectal cancer (CRC) is a complex disease related to environmental and genetic risk factors. Several studies have shown that susceptibility to complex diseases can be mediated by ancestral alleles. Using RNAi screening, CTNNBL1 was identified as a putative regulator of the Wnt signaling pathway, which plays a key role in colorectal carcinogenesis. Recently, single nucleotide polymorphisms (SNPs) in CTNNBL1 have been associated with obesity, a known risk factor for CRC. We investigated whether genetic variation in CTNNBL1 affects susceptibility to CRC and tested for signals of recent selection. We applied a tagging SNP approach that cover all known common variation in CTNNBL1 (allele frequency >5%; r2>0.8). A case-control study was carried out using two well-characterized study populations: a hospital-based Czech population composed of 751 sporadic cases and 755 controls and a family/early onset-based German population (697 cases and 644 controls). Genotyping was performed using allele specific PCR based TaqMan® assays (Applied Biosystems, Weiterstadt, Germany). In the Czech cohort, containing sporadic cases, the ancestral alleles of three SNPs showed evidence of association with CRC: rs2344481 (OR 1.44, 95%CI 1.06-1.95, dominant model), rs2281148 (OR 0.59, 95%CI 0.36-0.96, dominant model) and rs2235460 (OR 1.38, 95%CI 1.01-1.89, AA vs. GG). The associations were less prominent in the family/early onset-based German cohort. Data derived from several databases and statistical tests consistently pointed to a likely shaping of CTNNBL1 by positive selection. Further studies are needed to identify the actual function of CTNNBL1 and to validate the association results in other populations

Topics: Original Article
Publisher: e-Century Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3077237
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.