title: Fordyce granules and hereditary non-polyposis colorectal cancer syndrome.
abstract: BACKGROUND
  Germline mutations in mismatch repair (MMR) genes are found in only about half of clinically diagnosed families with hereditary non-polyposis colorectal cancer syndrome (HNPCC) (or Lynch syndrome). Early identification of gene carriers is essential to reduce cancer incidence and overall mortality.
  
  
  OBJECTIVE
  Recent evidence indicates an increase in size and number of sebaceous glands following activation of the hedgehog pathway, a crucial signalling pathway for animal development that is aberrantly activated in several types of cancer. Here we sought to assess a possible association between Fordyce granules (FGs-that is, ectopic sebaceous glands on the oral mucosa) and HNPCC.
  
  
  METHODS
  A total of 15 members of five different genetically unrelated HNPCC kindreds (MLH1 gene mutation n = 8; undetectable MLH1 protein at immunochemistry n = 4; clinical diagnosis n = 3) and 630 genetically unrelated age and sex matched healthy controls were examined. Following examination of the oral mucosa surface, subjects were categorised as either FGs positive or FGs negative.
  
  
  RESULTS
  Evidence of FGs was significantly associated with HNPCC (13/15 (86.7%) affected patients v 6/630 (0.95%) controls; p<0.0001), with a relative risk of 91.0 (95% confidence interval 40.05-206.76). The observed difference remained significant when carriers of germline mutations in MMR genes were considered (8/15 v 6/630; p<0.0001). The most common site for the FGs in HNPCC patients was the lower gingival and vestibular oral mucosa.
  
  
  CONCLUSIONS
  Our findings suggest that a previously unrecognised activation of the sebaceous glands system occurs in HNPCC. The observation could be of value for attending physicians in identifying affected families and/or increase the accuracy of the currently available molecular genetics screenings.
authors.affiliation: Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale M Bracci, 16-I-53100 Siena, Italy. defelice.claudio@libero.it
authors.forename: C
authors.initials: C
authors.lastname: De Felice
authors.forename: S
authors.initials: S
authors.lastname: Parrini
authors.forename: G
authors.initials: G
authors.lastname: Chitano
authors.forename: M
authors.initials: M
authors.lastname: Gentile
authors.forename: L
authors.initials: L
authors.lastname: Dipaola
authors.forename: G
authors.initials: G
authors.lastname: Latini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology*; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D012627:Sebaceous Glands / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1