Hereditary non-polyposis colorectal cancer (HNPCC) results from inactivating germline mutations in a set of DNA-mismatch-repair genes, of which the most clinically relevant are hMSH2 and hMLH1. Computer-assisted pedigree risk assessment tools are available to assist in the calculation of an individual's likelihood of bearing such a deleterious mutation. One such tool, cancergene version 3.4 (ht...

Recently, Zecevic et al. ( 1 ) reported an association between the size of the CArepeat sequence residing in the 5 ′ untranslated promoter region upstream of the start site of the IGF-1 gene and age of disease onset in 121 hereditary nonpolyposis colorectal cancer patients who harbored germline mutations in the mismatch repair (MMR) genes hMLH1 or hMSH2 ( 1 ). In their study, an association bet...

Background and aims: Germline mutations in mismatch repair (MMR) genes cause a greatly increased risk of cancer of the gastrointestinal and female reproductive tracts (hereditary non-polyposis colorectal cancer (HNPCC)). Loss of MMR expression is common in colorectal cancer (CRC) overall. Such loss is assumed to be acquired predominantly, although a population of CRC cases will include individu...

OBJECTIVES We studied the role of minor mismatch repair proteins (MMR) human MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes of renal cell carcinoma (RCC). METHODS Expression of MMR proteins hMLH1 and hMSH2 were investigated in 166 RCC tumors, containing the main subtypes by immunohistochemistry. Furthermore, each tumor was screened for microsatellite instabil...

The aim of this study was to investigate the clinical value of different criteria and to understand the relationship between genotype and phenotype in Chinese hereditary nonpolyposis colorectal cancer (HNPCC). A total of 116 unrelated probands of suspected HNPCC families from the Fudan Colorectal Registry were studied. A total of 32, 28, and 56 families fulfilled the Amsterdam criteria, the Fud...

BACKGROUND Hereditary non-polyposis colorectal cancer (HNPCC) is caused by germline mutations of mismatch repair genes, usually in hMLH1 or hMSH2. All earlier studies on penetrance except one population based study were conducted in HNPCC families and did not correct for the way in which these families were ascertained. OBJECTIVE To obtain estimates of the risk of colorectal cancer (CRC) and ...

There is conflicting evidence for the role of the mismatch repair (MMR) genes hMLH1 and hMSH2 in the transcription-coupled repair (TCR) pathway of nucleotide excision repair. In the present work, we have examined the role of these MMR genes in nucleotide excision repair using two reporter gene assays. AdHCMVlacZ is a replication-deficient recombinant adenovirus that expresses the beta-galactosi...

Alterations of the length of simple repetitive genomic sequences (microsatellite instability, MSI) characterize a distinct mechanism of colorectal carcinogenesis. Such MSI has been found to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) that involves mutation of the human mismatch repair genes hMSH2 and hMLH1 as well as many sporadic cancers of most tissue types. Although ...

CONTEXT Genetic testing for cancer predisposition is evolving from purely research applications to affecting clinical management. OBJECTIVE To determine how often genetic test results for hereditary nonpolyposis colorectal cancer (HNPCC) can be definitively interpreted and used to guide clinical management. DESIGN Case-series study conducted in 1996 to 1998 in which a complete sequence anal...