Lynch syndrome in a predominantly Afrocentric population: a clinicopathological and genetic study

We investigated the prevalence of Lynch syndrome as a hereditary cause of colon cancer in the young Jamaican colorectal cancer (CRC) population.

We identified patients aged 40 years or younger in whom primary CRC was diagnosed at the University Hospital of the West Indies from January 2004 to December 2008. We reviewed the medical records and hematoxylin and eosin (H&E)-stained histopathology slides. Tumour blocks were tested for microsatellite instability (MSI). Patients with MSI-high phenotype (MSI-H) tumours had genetic counselling, after which genomic DNA was extracted from peripheral blood to test for MLH1 and MSH2 germline mutations. Patients also had pedigree mapping.

There were 25 patients with CRC aged 40 years or younger with no history of hereditary colon cancer syndrome. The patients' mean age was 33 (range 21-40) years. Histopathologic review confirmed CRC in all patients; 8 of 25 (32%) showed morphologic features suggestive of MSI. We detected MSI-H in 5 of 23 (22%) tumour blocks tested. Review with H&E staining correctly identified 80% of cases positive for MSI-H. The false-positive rate and positive predictive value on H&E review was 50%. The negative predictive value of histomorphologic H&E review was 94%. Three patients were available for and had mutational analysis of DNA mismatch repair genes; 2 were positive for mutations in keeping with Lynch syndrome and 1 had MLH1 alterations of uncertain significance. All 3 met the Amsterdam criteria for hereditary nonpolyposis CRC.

Thirteen percent of the population had mutations in keeping with Lynch syndrome. This prevalence is similar to that reported for white populations.