The aim of the study was to determine the relationship between gene polymorphism Glu39Gly (c.116G>A) of the hMSH6 gene and the modulation of the risk of sporadic colorectal cancer in the Polish population.
To explore this possibility, we screened tumors from 41 patients with MSI-L CRC for hMSH6 mutations with conformation-sensitive gel electrophoresis (CSGE) and for hMSH6 protein expression by immunohistochemistry.
The three pathogenic variants included two colorectal cancers with MLH1 loss and high MSI and one endometrial cancer with MSH6 loss and microsatellite stability.
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline mutations in MisMatch Repair (MMR) genes, particularly in MLH1, MSH2 and MSH6.
CRC patients carrying monoallelic MUTYH mutations harbor more frequently concomitant MSH6 mutations than patients without them, thus suggesting that both genes could act cooperatively and confer together an increased CRC risk.
Hereditary non-polyposis colorectal cancer is the most common known genetic syndrome that predisposes to various types of cancer including gastric cancer and occures mainly due to pathogenic germline mutations in DNA mismatch repair (MMR) genes, such as MLH1, MSH2 and MSH6.
Approximately 15% of colorectal cancers (CRC) display MSI owing either to epigenetic silencing of MLH1 or a germline mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2.
CRC risks for POLE mutation carriers are sufficiently high to warrant consideration of colonoscopy screening and implementation of management guidelines recommended for MSH6 mutation carriers in cases of Lynch syndrome.
Eight novel MSH6 germline mutations in patients with familial and nonfamilial colorectal cancer selected by loss of protein expression in tumor tissue.
Germline mutations in the DNA mismatch repair (MMR) genes MSH2, MSH6, or MLH1 predispose to colorectal cancer (CRC) with an autosomal dominant inheritance pattern.
Most recently, MYH-associated polyposis (MAP) and an "atypical Lynch syndrome" related to the presence of MSH6 mutations have been linked to an increased risk of CRC.
The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals [CI], 25%-70%) for MLH1 mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6.
Lynch Syndrome (LS) is the most common dominantly inherited colorectal cancer (CRC) predisposition and is caused by a heterozygous germline defect in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2.
We identified 27 germ-line MMR variants in the 167 patients with a high-risk for HNPCC while only one germ-line mutation in hMSH6 was found in the late-onset CRC group.Of those, 23 were pathogenic mutations.
Data suggest that the frequency of MSH6 mutation is higher in hereditary non-polyposis colorectal cancer patients than in atypical hereditary non-polyposis colorectal cancer and sporadic patients.
The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2.
Twenty-nine patients (52.7%) developed CRC and extra-colonic tumors; of these, 15 patients (48.3%) had mutations in MLH1, 10 (58.8%) in MSH2, and 4 (57.1%) in MSH6.