open access: Perspectives - Diagnosing Lynch Syndrome: More Light at the End of the Tunnel

Diagnosing Lynch Syndrome: More Light at the End of the Tunnel

"Lynch syndrome is one of the most commonly inherited
cancer conditions, accounting for 2% to 4% of colorectal
cancer (CRC) cases. The population frequency of Lynch
syndrome is slightly more than one in 500 individuals (1).
In addition to a 50% to 80% lifetime risk of CRC, patients
with Lynch syndrome have a 40% to 60% risk of uterine
cancer and an elevated risk of ovarian, pancreatic, gastric,
upper-urinary tract, renal, biliary, small bowel, and central
nervous system (CNS) malignancies.

"Colorectal surveillance of persons with this condition leads to greatly reduced CRC incidence and mortality. Appropriately timed hysterectomy and ovarectomy likewise results in a reduced incidence of malignancies in these organs. The diagnosis of Lynch syndrome is thus critical to the prevention and early detection of cancer in affected persons and families, notwithstanding that the effectiveness of screening patients with Lynch syndrome for non colorectal and non uterine malignancies remains uncertain. As will be discussed later, the article by Yurgelun and colleagues in this issue of the journal provides an important new tool for the diagnosis of Lynch syndrome (2).
The major issue in Lynch syndrome remains failure to
diagnose for a variety of reasons......."

".....It seems that MSI or immunohistochemical
testing in uterine cancers may be as effective as in
CRCs and therefore should also be considered in evaluating
persons and families for Lynch syndrome (17, 18). Whether
tumor testing in other (nonuterine or noncolorectal)
Lynch-associated malignancies would be as effective is
unclear....."

"............Next generation sequencing also may soon
be available for individual testing at reasonable costs.
Such new testing developments may well make direct-to-genetic
testing based on risk increasingly attractive. At
some point, general testing for an inherited syndrome
without regard to risk may even become a reality, which would get the diagnosis of Lynch syndrome out of the tunnel altogether."