Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer

Abstract

BACKGROUND: Lynch syndrome (LS; hereditary nonpolyposis colorectal cancer) is a common cause of hereditary colorectal cancer (CRC). CRC is the most common cancer diagnosed among males in Saudi Arabia but to the authors' knowledge there is a lack of data regarding the prevalence of LS in patients with CRC. There currently are no clear guidelines for the selection criteria for these patients to screen for LS. METHODS: A comprehensive molecular characterization was performed in a cohort of 807 CRC cases by immunohistochemical and microsatellite analysis using polymerase chain reaction. BRAF mutation screening, high CpG island methylator phenotype, and analysis for germline mutations were performed in 425 CRC samples. These were all high microsatellite instability (MSI-H) samples (91 cases), all low MSI samples (143 cases), and selected cases from the microsatellite stable group (191 cases) that met revised Bethesda guidelines. RESULTS: Polymerase chain reaction identified 91 MSI-H cases (11.3%) and sequencing revealed mismatch repair germline mutations in 8 CRC cases only. Of the total of 807 CRC cases, these 8 cases (0.99%) were MSI-H, met the revised Bethesda guidelines, and did not harbor BRAF mutations. CONCLUSIONS: The results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI-H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives. Cancer 2015;121:1762-71.

Prevalence of Lynch syndrome and Lynch-like syndrome among patients with colorectal cancer in a Japanese hospital-based population

“…This study demonstrated that the most commonly occurring deleterious germline mutation was that noted in MSH2 (56%, 5/9 cases), which was in agreement with other studies from the USA (8), Finland (33), Spain (11), Slovenia (34) and Saudi Arabia (35). The reason for the lower incidence of the MLH1 germline mutation (only one case) is unclear, despite the search for the possibility of germline MLH1 epimutations.…”

Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome

“…In general, published detection rates have ranged an average of 2% to 3% for individuals with either CRC or EC, although there is some variation between different reports. 6,7,11,[15][16][17][18][19][20][21][22] Our detection rate may be lower for several reasons. Only one-half of all patients who were referred for genetic counseling ultimately attended a counseling session.…”

Risk of subsequent primary malignancies among patients with prior colorectal cancer: a population-based cohort study

“…Most previous studies report a low incidence of hereditary CRC. Lynch syndrome, the most common hereditary malignancy, has an incidence of 1% and accounts for 2%–5% of all CRC cases,26,27 which is less than the cumulative incidence of multiple PMs. Hereditary CRC may be recognized as a typical representative group for multiple primary cancers.…”