title: DLX1 and MMP3 contribute to oral clefts with and without positive family history of cancer.
abstract: OBJECTIVE
  It has been suggested that oral clefts and cancer share a common genetic background. This study aimed to investigate the epidemiological and molecular association between oral clefts and cancer.
  
  
  METHODS
  One hundred forty-eight nuclear families with oral clefts and 162 subjects with no birth defect were recruited. Data on self-reported family history of cancer among first, second, and third degree relatives of each patient were collected via a structured questionnaire. We also investigated the association between polymorphisms in the genes AXIN2, BMP2, BMP4, BMP7, DLX1, DLX2, and MMP3 and oral cleft with and without history of cancer. Markers in these genes were genotyped using real time PCR. Chi-square and t-test were used to assess the differences about self-reported family history of cancer between oral cleft and non-cleft individuals. The transmission disequilibrium test (TDT) was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring.
  
  
  RESULTS
  Families with oral clefts had an increased risk of having a family history of cancer (p=0.01; odds ratio=1.79; 95% confidence interval, 1.07-1.87). TDT results showed an association between DLX1 and cleft lip and palate, in which the A allele was undertransmited (p=0.022). For MMP3, G was undertransmited among affected progeny (p=0.019) in cleft palate subgroup.
  
  
  CONCLUSIONS
  Oral clefts were associated with positive self-reported family history of cancer and with variants in DLX1 and MMP3. The association between oral clefts and cancer raises interesting possibilities to identify risk markers for cancer.
authors.affiliation: Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, RJ, Brazil.
authors.forename: Ticiana M
authors.initials: TM
authors.lastname: Sabóia
authors.affiliation: Unit of Clinical Research, Fluminense Federal University, Niterói, RJ, Brazil.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Reis
authors.affiliation: Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, RJ, Brazil.
authors.forename: Ângela M C
authors.initials: ÂM
authors.lastname: Martins
authors.affiliation: Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, RJ, Brazil.
authors.forename: Helena F
authors.initials: HF
authors.lastname: Romanos
authors.affiliation: Discipline of Pediatric Dentistry, School of Dentistry, Veiga de Almeida University, RJ, Brazil.
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tannure
authors.affiliation: Unit of Clinical Research, Fluminense Federal University, Niterói, RJ, Brazil; Bioengineering Program, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ, Brazil.
authors.forename: José Mauro
authors.initials: JM
authors.lastname: Granjeiro
authors.affiliation: Department of Oral Biology and Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
authors.affiliation: Unit of Clinical Research, Fluminense Federal University, Niterói, RJ, Brazil; Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, RJ, Brazil. Electronic address: leonardoantunes@id.uff.br.
authors.forename: Leonardo S
authors.initials: LS
authors.lastname: Antunes
authors.affiliation: Department of Oral Biology and Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Küchler
authors.affiliation: Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, RJ, Brazil.
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Costa
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011795:Surveys and Questionnaires; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: Cancer; Genes; Oral clefts