The incidence of Lynch syndrome
In 1990, the International Collaborating Group (ICG) on hereditary nonpolyposis colorectal cancer (HNPCC) met in Amsterdam and the ‘Amsterdam’ clinical criteria were developed to help coordinate research into this disease. By setting a threshold of three affected family members diagnosed with colorectal cancer over at least two generations , one of whom was a first-degree relative of the other two, and requiring that one of these be diagnosed less than 50 years of age with Familial Adenomatous Polyposis (FAP) having been excluded, it was envisioned that only families with a unique genetic background would be included. It was acknowledged that the Amsterdam criteria were very stringent and would exclude many cases of the disease if the family size was too small. The goal was identify families which were suitable for linkage analysis studies to find the causative gene(s).
In 1999, the ICG-HNPCC recognized the importance of non-colonic malignancies and revised the Amsterdam criteria to include tumours of the small intestine, ureter and renal pelvis to the spectrum associated with the syndrome (Amsterdam criteria II).
The cornerstone of both Amsterdam I & II criteria is the occurrence of a Lynch syndrome tumour in two close relatives of the proband, therefore, the smaller the family size the more unlikely the family tree will fulfil these criteria. An adopted child without knowledge of his biological family is an extreme example, false paternity, incomplete penetrance, outright denial and/or the lack of co-operation of family members are other reasons why documenting family histories will not be informative. As family size is generally decreasing, the family history based definitions for Lynch Syndrome will become less clear and less relevant.
The prevalence of Lynch Syndrome in colorectal and endometrial cancer patients is 1-3%. If one defines Lynch syndrome (LS) as carriership of a pathogenic mismatch repair (MMR) mutation, therefore in Ireland approximately 12 cases of endometrial cancer per annum and 75 cases of colon cancer per annum are due to Lynch syndrome.
On extrapolation to the entire population, the incidence of LS is between 1:2000 and 1:660 however as all screening methods are less than 100% sensitive, the above figures are underestimates.
Michael Farrell, RGN, M.Sc. in Molecular Medicine, CNS in Cancer Genetics. 4th October 2015.