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Insights from studies with oral cleft genes suggest associations between WNT-pathway genes and risk of oral cancer

Andrade Filho, PA and Letra, A and Cramer, A and Prasad, JL and Garlet, GP and Vieira, AR and Ferris, RL and Menezes, R (2011) Insights from studies with oral cleft genes suggest associations between WNT-pathway genes and risk of oral cancer. Journal of Dental Research, 90 (6). 740 - 746. ISSN 0022-0345

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Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the malignant neoplasms that arise in the mucosa of the upper aerodigestive tract. Recent studies of cleft lip/palate have shown the association of genes involved in cancer. WNT pathway genes have been associated with several types of cancer and recently with cleft lip/palate. To investigate if genes associated with cleft lip/palate were also associated with oral cancer, we genotyped 188 individuals with OSCC and 225 control individuals for markers in AXIN2, AXIN1, GSK3β, WNT3A, WNT5A, WNT8A, WNT11, WNT3, and WNT9B. Statistical analysis was performed with PLINK 1.06 software to test for differences in allele frequencies of each polymorphism between cases and controls. We found association of SNPs in GSK3B (p = 0.0008) and WNT11 (p = 0.03) with OSCC. We also found overtransmission of GSK3B haplotypes in OSCC cases. Expression analyses showed up-regulation of WNT3A, GSK3B, and AXIN1 and down-regulation of WNT11 in OSCC in comparison with control tissues (P < 0.001). Additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting and oral cancer. © 2011 International & American Associations for Dental Research.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Andrade Filho, PA
Letra, A
Cramer, A
Prasad, JLjlp92@pitt.eduJLP92
Garlet, GP
Vieira, ARarv11@pitt.eduARV11
Ferris, RL
Menezes, R
Date: 1 June 2011
Date Type: Publication
Journal or Publication Title: Journal of Dental Research
Volume: 90
Number: 6
Page Range: 740 - 746
DOI or Unique Handle: 10.1177/0022034511401622
Schools and Programs: School of Dental Medicine > Dental Science
Refereed: Yes
ISSN: 0022-0345
MeSH Headings: Adaptor Proteins, Signal Transducing--genetics; Adult; Aged; Aged, 80 and over; Axin Protein; Carcinoma, Squamous Cell--genetics; Case-Control Studies; Cleft Lip--genetics; Cleft Palate--genetics; Female; Gene Frequency; Glycogen Synthase Kinase 3--genetics; Humans; Male; Middle Aged; Mouth Neoplasms--genetics; Neoplasm Proteins--genetics; Polymorphism, Single Nucleotide; Repressor Proteins--genetics; Signal Transduction--genetics; Wnt Proteins--genetics; Wnt3 Protein; Wnt3A Protein
Other ID: NLM NIHMS280471, NLM PMC3092817
PubMed Central ID: PMC3092817
PubMed ID: 21393552
Date Deposited: 24 Sep 2012 20:51
Last Modified: 20 Feb 2020 13:55


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