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open access
Background
Lynch
syndrome is a multi-tumor syndrome with the highest risks for
colorectal cancer and endometrial cancer though a number of other tumor
types, e.g. cancer of the urinary tract, the small bowel and the
ventricle, ovarian cancer, brain tumors and skin tumors develop at
increased incidence [1, 2].
Other tumor types assumed to represent sporadic tumors in families with
hereditary cancer, e.g. breast cancer, pancreatic cancer and sarcoma
may indeed develop as part of the syndrome. This is suggested based on
identification of mismatch repair (MMR) defective tumors of these
subtypes and demonstration of an increased risk of these tumor types in
mutation carriers [3–10].
Prostate
cancer is the most common tumor type in men in the Western world with
an estimated lifetime risk of 18 % and a median age at diagnosis of
67 years [1]. Worldwide, prostate cancer is the sixth common tumor with more than 250,000 deaths annually [11].
In Denmark, prostate cancer constitutes 23 % of all male cancers with
an estimated risk of 10 % for disease development before age 75 [12].
The role of prostate cancer in Lynch syndrome is unresolved though
molecular investigations and epidemiologic studies have suggested a
potential link to the syndrome [1, 8, 13].
The MMR system has been suggested to influence prostate carcinogenesis
e.g. through an increased risk of prostate cancer linked to single
nucleotide polymorphisms in MLH1 and MSH3, and a role for complex structural rearrangements in MSH2 and MSH6 as a mechanism underlying the hypermutation in aggressive prostate cancer [14–20].
We assessed the role of prostate cancer in the Danish Lynch syndrome
cohort with characterization of MMR status and risk estimates.....
Conclusions
The
Danish Lynch syndrome cohort contains 28 prostate cancers that
developed at a median age of 63 years, showed high Gleason scores and
frequent TILs. The tumors were predominantly linked to MSH2
mutations. Frequent MMR defects consistent with the underlying germline
defects suggest that prostate cancer is included in Lynch syndrome
tumor spectrum and should be considered during genetic counseling.
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