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Published January 1, 2018 | Version v1
Journal article Open

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

Creators

  • 1. Univ Texas Hlth Sci Ctr Houston, Sch Dent, Ctr Craniofacial Res, Houston, TX 77054 USA
  • 2. Univ Iowa, Coll Dent, Iowa Inst Oral Hlth, Iowa City, IA 52242 USA
  • 3. Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol & Human Genet, Houston, TX 77054 USA
  • 4. Tufts Univ, Dept Orthodont, Boston, MA 02111 USA
  • 5. Istanbul Univ, Sch Med, Dept Med Genet, TR-34093 Istanbul, Turkey

Description

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 x 10(-10)) and DUSP10 rs6687758 (P = 1.25 x 10(-9)), and positive association found with CASC8 rs10505477 (P = 8.2 x 10(-5)). 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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