Abstract
BackgroundThe prevalence of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is 2 to 5% in the Caucasian population. HNPCC is caused by genomic mutations in DNA mismatch repair genes (MMR), namely MLH1, MSH2, MSH6, PMS2, and EPCAM. A non-hereditary, acquired process of hypermethylation of the MLH1 promoter can also lead to silencing of MLH1 protein expression. Diagnosis of HNPCC in patients with colorectal and other related cancers is important in the clinical treatment and surveillance of related cancers. The prevalence and clinical characteristics of HNPCC in Asian colorectal cancer patients has been reported in small studies and unique features have been suggested.MethodsWe retrospectively reviewed the clinical characteristics of Asian patients who were diagnosed of colon cancer between 1/2002 and 6/2015, and performed IHC for four MMR protein expressions on tumor specimens as a screening test for HNPCC, followed by confirmatory tests of genomic sequencing and hypermethylation analysis.ResultsOne hundred forty-three patients were identified. Thirty-one patients were diagnosed younger than 50 years old, while 112 patients were diagnosed older than 50 years old. Six cases of HNPCC were found with a prevalence of 4.19%. The prevalence in the group of patients diagnosed younger than 50 years old is 16.1%, and that in patients diagnosed older than 50 years old is 0.89%. All patients with HNPCC had family histories of colon or gastric cancer. Tumor locations in the HNPCC patients were predominantly in the descending or sigmoid colon (67%). Half of the HNPCC patients had MSH6 mutations. Hypermethylation of the MLH1 gene was only present in 2.80% of the patients.ConclusionThe prevalence of HNPCC is high in patients younger than 50 years old and extremely low in those older than 50 years old. These results may be useful in the future development of guidelines for HNPCC laboratory screening among Asian patients. The pathological and clinical features of HNPCC in this group of Asian immigrant patients are more similar to those reported on Asian patients in their home countries than to Caucasian patients in Western countries, and will warrant further large-scale evaluation.
Highlights
The prevalence of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is 2 to 5% in the Caucasian population
We evaluated the prevalence, clinical characteristics, and mutation preferences of HNPCC in immigrant Asian patients newly diagnosed of colorectal cancer
To assess whether there is a difference in the clinical presentation of Asian patients with HNPCC versus Caucasian patients, we reviewed our data in the context of several published studies on Asian patients including patients from the Northern or Southern part of Mainland China [17,18,19, 21,22,23]
Summary
The prevalence of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is 2 to 5% in the Caucasian population. HNPCC is caused by genomic mutations in DNA mismatch repair genes (MMR), namely MLH1, MSH2, MSH6, PMS2, and EPCAM. Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch Syndrome is an inherited cancer susceptibility syndrome that predisposes individuals to colorectal cancer as well as extra-colonic cancers, such as endometrial, gastric, ovarian, urothelial and others, with an onset usually before 50 years old [1]. It is characterized by germline mutations in one of the several DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6, PMS2, and EPCAM. While the gold standard for HNPCC diagnosis is genomic sequencing, screening strategies testing for loss of protein expression by IHC versus polymerase chain reaction detection of the MSI panel are considered to be equivalent [4, 5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
