Autosomal dominant condition, most often linked to colorectal and endometrial cancer.
Also known as hereditary non polyposis colorectal cancer (HNPCC).
UTUC is the 3rd most common cancer in Lynch syndrome.
Also increased risk of ovarian, stomach, small bowel, HPB, CNS, skin and other urological cancers.
Pathogenesis:
Germline mutation in one of 4 mismatch repair (MMR) genes – MLH1, MLH2, MSH6 or PMS2
These mutations cause a defect in the proof reading system of DNA replication resulting in errors -> most often in regions of short repeating sequences called microsatellites (microsatellite instability)
Cumulative lifetime risk of 2.9 % for UTUC in patients with Lynch syndrome (RR at least 14 to normal population)
- Compared to ‘normal’ UTUC – more commonly women and younger age
- Estimate maybe 1 – 5 % of UTUC is Lynch driven
Emerging evidence of bladder cancer and prostate cancer involvement in Lynch syndrome also.
Pragmatic points:
- Consider asking pathologist to look for mismatch repair gene mutations if suspicious (young age, strong family history)
- Consider genetic testing, counselling and implications for families
- How to screen patients with known Lynch syndrome?
- Yearly urine microscopy?
- Delayed phase imaging in conjunction with follow up for CRC?