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Colorectal Cancer-Associated Genes Are Associated with Tooth Agenesis and May Have a Role in Tooth Development
Journal article   Open access   Peer reviewed

Colorectal Cancer-Associated Genes Are Associated with Tooth Agenesis and May Have a Role in Tooth Development

Meredith A Williams, Claudia Biguetti, Miguel Romero-Bustillos, Kanwal Maheshwari, Nuriye Dinckan, Franco Cavalla, Xiaoming Liu, Renato Silva, Sercan Akyalcin, Z Oya Uyguner, …
Scientific reports, Vol.8(1), pp.2979-10
02/14/2018
DOI: 10.1038/s41598-018-21368-z
PMCID: PMC5813178
PMID: 29445242
url
https://doi.org/10.1038/s41598-018-21368-zView
Published (Version of record) Open Access

Abstract

Previously reported co-occurrence of colorectal cancer (CRC) and tooth agenesis (TA) and the overlap in disease-associated gene variants suggest involvement of similar molecular pathways. Here, we took an unbiased approach and tested genome-wide significant CRC-associated variants for association with isolated TA. Thirty single nucleotide variants (SNVs) in CRC-predisposing genes/loci were genotyped in a discovery dataset composed of 440 individuals with and without isolated TA. Genome-wide significant associations were found between TA and ATF1 rs11169552 (P = 4.36 × 10 ) and DUSP10 rs6687758 (P = 1.25 × 10 ), and positive association found with CASC8 rs10505477 (P = 8.2 × 10 ). Additional CRC marker haplotypes were also significantly associated with TA. Genotyping an independent dataset consisting of 52 cases with TA and 427 controls confirmed the association with CASC8. Atf1 and Dusp10 expression was detected in the mouse developing teeth from early bud stages to the formation of the complete tooth, suggesting a potential role for these genes and their encoded proteins in tooth development. While their individual contributions in tooth development remain to be elucidated, these genes may be considered candidates to be tested in additional populations.

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