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

Abstract

Objective: We investigated the prevalence of Lynch syndrome and Lynch-like syndrome among Japanese colorectal cancer patients, as there have been no credible data from Japan. Methods: Immunohistochemical analyses for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were carried out in surgically resected, formalin-fixed paraffin-embedded specimens obtained from 1,234 newly diagnosed colorectal cancer patients between March 2005 and April 2014. The presence/absence of the BRAF V600E mutation and hypermethylation of the MLH1 promoter was analyzed where necessary. Genetic testing was finally undertaken in patients suspected as having Lynch syndrome. Results: By the universal screening approach with immunohistochemical analysis for mismatch repair proteins followed by analyses for the BRAF V600E mutation and MLH1 promoter methylation status, 11 (0.9%) of the 1,234 patients were identified as candidates for genetic testing. Out of the 11 patients, 9 (0.7%) were finally diagnosed as having Lynch syndrome; the responsible genes included MLH1 (n = 1), MSH2 (n = 4), EPCAM (n = 1) and MSH6 (n = 3). The remaining two patients (0.2%) were regarded as having Lynch-like syndrome, since biallelic somatic deletion of the relevant mismatch repair genes was detected in the absence of germline mismatch repair alterations. None of the cases was identified as having germline MLH1 epimutation. Conclusions: The prevalence of Lynch syndrome among all newly diagnosed cases of colorectal cancer in Japan is in the same range as that recently reported by studies in Western population. The prevalence of Lynch-like syndrome seems to be extremely low.

Secondary Breast, Ovarian, and Uterine Cancers After Colorectal Cancer: A Nationwide Population-Based Cohort Study in Korea

“…22 However, HNPCC is a very rare disease, accounting for <1% of all CRC cases. 23 Evans et al 16 reported that patients with HNPCC had a 0.2% to 2% risk of developing primary carcinomas, with the exception of ovarian cancer. Women harboring a deleterious mutation in BRCA1 or BRCA2 , which encodes tumor suppressors, have an elevated risk of developing breast or ovarian cancer, as well as an elevated risk of CRC.…”

Population-based Screening for Hereditary Colorectal Cancer Variants in Japan

“…The prevalence of hereditary cancers varies significantly in different populations, and Japanese CRC patients have approximately 1% prevalence of MMR gene mutations. 10 Variant data of non-European populations are still limited, 11 leading to difficulties in interpreting variants of cancer-predisposing genes in multiethnic populations.…”

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

“…Furthermore, approximately 61.9% of deficient MMR tumors were indeed attributable to germline MMR gene mutations by in-depth molecular analysis, and Latino patients with Lynch syndrome develop cancer at a younger age and have a higher percentage of rectal cancers and advanced disease, which is consistent with observations in other studies [ 40 ]. The incidence of Lynch syndrome among diagnosed CRC patients in Japan is 0.7%, which is slightly lower than that reported previously but within the same range (0.7–3.7%) as that in recent investigations [ 41 ]. The CRC incidence in Finnish MLH1 mutation carriers was lower than that in non-Finnish carriers, but not significantly [ 42 ].…”