We screened 251 patients with hereditary non-polyposis colorectal cancer who were unrelated, had pathogenic germline mutations in MSH2 (n=141) or MLH1 (n=110), and had colorectal carcinoma as the first tumour, for variation at codon 462 of RNASEL and compared them with 439 healthy controls.
Lynch syndrome is one of the most common hereditary colorectal cancer (CRC) syndrome and is caused by germline mutations of MLH1, MSH2 and more rarely MSH6, PMS2, MLH3 genes.
When considering the genetics of CRC, only 10% of cases are inherited and only 2-6% can be ascribed to the highly penetrant genes, such as APC, hMLH and hMSH2.
The objective of the study was to investigate the prevalence of MLH1/MSH2 mutation carriers among Moroccan patients with colorectal cancer (CRC) in a hospital-based cohort.
In addition, MSH2 1168T showed trends toward association with CRC and GC in young (<50 yr) sporadic disease patients (OR = 10.97 and 17.15, respectively).
MSH6 mutation carriers have later age of onset of both colorectal cancer (62 vs. 51 years) and endometrial cancer (58 vs. 48 years) and a larger proportion of endometrial cancer than MLH1 or MSH2 mutation carriers.
The discovery of DNA mismatch repair (MMR) genes, inclusive of hMSH2, hMLH1, hPMS2, and hMSH6, has enabled the identification of who has and who does not have inordinately increased susceptibility to CRC as well as a litany of extracolonic cancers.
Lynch syndrome (hereditary nonpolyposis colorectal cancer; HNPCC) is an autosomal-dominant cancer predisposition syndrome that increases risk for multiple cancers, including colon, endometrial, and ovarian cancer.
Purpose Most existing literature describes Lynch syndrome (LS) as a hereditary syndrome leading to high risks of colorectal cancer (CRC) and endometrial cancer mainly as a result of mutations in MLH1 and MSH2.
Our aim was to elucidate the molecular basis of MSH2-deficient LS-suspected cases using a comprehensive analysis of colorectal cancer (CRC)-associated genes at germline and somatic level.
Overall, the penetrance of colorectal cancer appears to be significantly decreased (p<0.001) among the MSH6 mutation carriers in this family when compared with MSH2 and MLH1 carriers (32% by the age of 80 v >80%).
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.
The higher gene expression of MSH2 in responders and the trend for predicting overall survival indicates a predictive value of this marker in the treatment of advanced CRC with capecitabine.
We genotyped the MLH1 and MSH2 genes in patients suffering from Lynch syndrome and in 11 unrelated patients who were diagnosed with colorectal cancer and had subsequently undergone surgery.
The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumours.
Our results indicate that mutations in the promoter region of hMSH2 have a limited role in development of suspected HNPCC and sporadic early onset colorectal cancer.
Compared to MSH2 mutation carriers, MLH1 mutation-positive individuals were more likely to have a strong family history of CRC and LS associated cancers.
Human MutS homologue 2 (hMSH2), originally identified as a human homologue of the bacterial MutS, is a tumour suppressor gene frequently mutated in hereditary non-polyposis colorectal cancer.
Based upon these results, we conclude that most MLH1 and MSH2 missense changes are unlikely to act as major causative factors in colorectal cancer susceptibility and development.