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

Joseph M. Plummer, Sheray N. Chin, Melyssa Aronson, Rondell Graham, Nadia P. Williams, Bharati Bapat, Gillian Wharfe, Aaron Pollett, Steven Gallinger

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: We investigated the prevalence of Lynch syndrome as a hereditary cause of colon cancer in the young Jamaican colorectal cancer (CRC) population. Methods: 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. Results: 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. Conclusion: Thirteen percent of the population had mutations in keeping with Lynch syndrome. This prevalence is similar to that reported for white populations.

Original languageEnglish (US)
Pages (from-to)294-300
Number of pages7
JournalCanadian Journal of Surgery
Volume55
Issue number5
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
Colorectal Neoplasms
Population
Colonic Neoplasms
Hereditary Neoplastic Syndromes
West Indies
Neoplasms
Mutation
DNA Mismatch Repair
Germ-Line Mutation
Genetic Counseling
Hematologic Tests
Hematoxylin
Pedigree
Eosine Yellowish-(YS)
Medical Records
Staining and Labeling
Phenotype
DNA

ASJC Scopus subject areas

  • Surgery

Cite this

Plummer, J. M., Chin, S. N., Aronson, M., Graham, R., Williams, N. P., Bapat, B., ... Gallinger, S. (2012). Lynch syndrome in a predominantly Afrocentric population: A clinicopathological and genetic study. Canadian Journal of Surgery, 55(5), 294-300. https://doi.org/10.1503/cjs.037410

Lynch syndrome in a predominantly Afrocentric population : A clinicopathological and genetic study. / Plummer, Joseph M.; Chin, Sheray N.; Aronson, Melyssa; Graham, Rondell; Williams, Nadia P.; Bapat, Bharati; Wharfe, Gillian; Pollett, Aaron; Gallinger, Steven.

In: Canadian Journal of Surgery, Vol. 55, No. 5, 01.01.2012, p. 294-300.

Research output: Contribution to journalArticle

Plummer, JM, Chin, SN, Aronson, M, Graham, R, Williams, NP, Bapat, B, Wharfe, G, Pollett, A & Gallinger, S 2012, 'Lynch syndrome in a predominantly Afrocentric population: A clinicopathological and genetic study', Canadian Journal of Surgery, vol. 55, no. 5, pp. 294-300. https://doi.org/10.1503/cjs.037410
Plummer, Joseph M. ; Chin, Sheray N. ; Aronson, Melyssa ; Graham, Rondell ; Williams, Nadia P. ; Bapat, Bharati ; Wharfe, Gillian ; Pollett, Aaron ; Gallinger, Steven. / Lynch syndrome in a predominantly Afrocentric population : A clinicopathological and genetic study. In: Canadian Journal of Surgery. 2012 ; Vol. 55, No. 5. pp. 294-300.
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abstract = "Background: We investigated the prevalence of Lynch syndrome as a hereditary cause of colon cancer in the young Jamaican colorectal cancer (CRC) population. Methods: 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. Results: 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. Conclusion: Thirteen percent of the population had mutations in keeping with Lynch syndrome. This prevalence is similar to that reported for white populations.",
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N2 - Background: We investigated the prevalence of Lynch syndrome as a hereditary cause of colon cancer in the young Jamaican colorectal cancer (CRC) population. Methods: 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. Results: 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. Conclusion: Thirteen percent of the population had mutations in keeping with Lynch syndrome. This prevalence is similar to that reported for white populations.

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