COLORECTAL CANCER

Fordyce granules and hereditary non-polyposis colorectal cancer syndrome

C De Felice¹, S Parrini², G Chitano³, M Gentile⁴, L Dipaola³, G Latini⁵

¹ Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese, Policlinico "Le Scotte", Siena, Italy
² Department of Odontostomatological Sciences, University of Siena, Italy
³ Euro Mediterranean Scientific Biomedical Institute (ISBEM), Brindisi, Italy
⁴ Medical Genetic Unit, Hospital Di Venere, Bari, Italy
⁵ Division of Neonatology, Perrino Hospital, Brindisi, Italy, and Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), Lecce Section, Italy

Correspondence to:
Dr C De Felice
Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale M Bracci, 16-I-53100 Siena, Italy; defelice.claudio{at}libero.it

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.

Aims: 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.

Abbreviations: HNPCC, hereditary non-polyposis colorectal cancer; MMR, mismatch repair; CRC, colorectal carcinoma; FGs, Fordyce granules; Hh, hedgehog; MSI, microsatellite instability; MTS, Muir-Torre syndrome

Keywords: colorectal neoplasms; hereditary non-polyposis/diagnosis; fordyce granules; sebaceous glands; physical examination

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller
Gut 2005 54: 1209. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• De Felice, C, Gentile, M, Barducci, A, Bellosi, A, Parrini, S, Chitano, G, Latini, G (2006). Abnormal oral mucosal light reflectance: a new clinical marker of high risk for colorectal cancer. Gut 55: 1436-1439 [Abstract] [Full Text]