Content area
Full Text
Hereditary non-polyposis colorectal cancer syndrome (HNPCC) (or Lynch syndrome) is the most common form of hereditary colorectal cancer (CRC), 1, 2 caused by autosomal dominantly inherited germline mutations in mismatch repair (MMR) genes. Mutation carriers have a lifetime risk of >80% of developing CRC, together with an excess of extracolonic cancers at an early age. 3, 4 MLH1 and MSH2 accounts for almost 90% of identified mutations while MSH6 accounts for approximately 10%; mutations in PMS2 , MLH3 , and EXO1 have also been reported. 1, 2 Early identification of HNPCC gene carriers is essential to reduce cancer incidence and overall mortality. 1, 3, 4 However, the germline mutations in MMR genes can be established in only about half of clinically diagnosed HNPCC families, 1 while with the single exception of the rare Muir-Torre syndrome (MTS) variant (OMIM #158230), 5, 6 no obvious phenotypical physical stigmata aiding in the diagnosis exist. As a consequence, the actual frequency of HNPCC in the general population remains unknown. Theoretical reasons indicate a prevalence of 1:350 to 1:1700, while more conservative estimates are 2-7% of the total CRC cases, which suggests that HNPCC is currently underdiagnosed, 4 with devastating clinical consequences.
Fordyce granules (FGs) 7, 8 (that is, intraoral ectopic sebaceous glands) are thought to be benign common lesions on the oral mucosa of adults subjects. Their prevalence rates increase from childhood (0.2%) 9 to adulthood (0.97%), and rates are slightly higher in adult males (1.77%) than females (0.52%). 10 No correlations between FGs and systemic diseases are known to date. Recent evidence indicates an increase in size and number of sebaceous glands following activation of the hedgehog (Hh) pathway, 11 a crucial signalling pathway for animal development that is aberrantly activated in several types of cancer. 12, 13 Here we sought to assess a possible association between HNPCC and FGs.
METHODS
A total of 15 surviving members of five different genetically unrelated HNPCC kindreds (seven males, eight females; age at examination 53.7 (SD15.1) years; family 1, n = 4; family 2, n = 4; family 3, n = 1; family 4, n = 3; family 5, n = 3) originating from the Taranto and Brindisi areas of southern Italy were examined. All families fulfilled the Amsterdam criteria,...