Genotypic and Phenotypic Characteristics of Hereditary Colorectal Cancer (original) (raw)
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Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC)
Familial Cancer, 2008
The family histories of 130 individuals with documented hereditary non-polyposis colorectal cancer (HNPCC) (caused by mutations in mismatch-repair (MMR) genes MSH2 (n = 64), MLH1 (n = 62) or MSH6 (n = 4)) were obtained, and incidence of cancers in those families was compared to that in the general population. There were a total of 982 cancers in 723 individuals. Colorectal cancer (CRC) was the commonest type (64% and 55% in individuals from families with germline MLH1 and MSH2 mutations respectively). Median age at Keywords Lynch syndrome Á HNPCC Á Gene analysis Á Familial relative risk Á Clustering Abbreviations AER absolute excess risk CNS central nervous system
Hereditary non-polyposis colorectal cancer — morphologies, genes and mutations
Mutation Research-fundamental and Molecular Mechanisms of Mutagenesis, 1994
Mutations in human homologue of the yeast DNA mismatch repair gene MSH2 (equivalent to bacterial MutS) cause the condition heredity non-polyposis colorectal cancer (HNPCC). Cancers in HNPCC originate within bengin neoplastic polyps termed adenomas. Adenomas are clonal and each may serve as a marker of a single initiating mutation. The progression of adenomas is marked by increasing size, dysplasia and villosity. These characteristics can be taken as the morphological counterparts of the stepwise accumulations implicating ioncogenes and tumour suppressor genes. The aim of this study was to link the morphogenesis of heredity colorectal cancer with recent insights into the role of DNA mismatch repair genes. The frequency and anatomical distribution of adenomas in at-risk members of HNPCC families was the same as in an autopsy population. This suggests that the HNPCC gene does not initiate the process of neoplastic transformation. On the other hand, adenomas in at-risk members of HNPCC families were more likely to show villosity (p<0.001), high grade dysplasia (p=0.002) and probably increased size (p=0.15). These findings are consistent with the observation that the HNPCC gene causes DNA replication errors to develop and accumulate within neoplastic but not normal tissue. The effect of the HNPCC gene is to accelerate the progression of adenoma to carcinoma, but not to initiate adenoma development.
2008
Each year 3500 people in Switzerland are diagnosed with colorectal cancer. Approximately 20 percent of all affected patients have two or more first or second-degree relatives with colorectal cancer (at-risk family members). About five percent of these are inherited in an autosomal dominant manner. present in a hemizygous state in the tumor. Furthermore, 100 healthy probands did not carry the alteration and sequence and amino acid alignment with vertebrates showed that it is located in a conserved region of the gene. Taken together, our findings indicate that the alteration in MSH3 may indeed be pathogenic. Recently, another FAP susceptibility gene besides APC was identified. It was shown that biallelic germline mutations in the human homologue of the base excision repair gene MutY (MYH) cause a phenotype of multiple colorectal adenomas and carcinomas, thus describing for the first time an autosomal recessively inherited CRC predisposition. This third part of this thesis aimed to assess the frequency of MYH mutation carriers within a Swiss cohort of 79 unrelated polyposis patients. In addition, comparisons have been made between MYH mutation carriers and APC mutation-negative individuals to establish genotype-phenotype correlations in this cohort of patients. The results of the study were published
2002
Advances in the molecular biology of colorectal cancer (CRC) broadened our understanding of this disease, but also provided insight into the pathogenesis of sporadic and inherited CRC. Mutations of APC gene are responsible for familial adenomatous polyposis (FAP), but mutations in six mismatch repair (MMR) genes: MSH2, MLH1, PMS1, PMS2, MSH6 and MSH3 for hereditary non-polyposis colorectal cancer (HNPCC). Development of genetic tests for detection of reported mutations of genes would make it possible to diagnose gene carriers and to discover CRC in early stage.
Genetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis
British Medical Bulletin, 2002
Familial adenomatous polyposis and hereditary non-polyposis colorectal cancer are dominantly inherited conditions with 100% and 80% life-time risk of developing colorectal cancer, respectively. The genetic mutations responsible for these two conditions lie in the adenomatous polyposis coli (APC) and mismatch repair genes. These same genes also play a key role in the formation of sporadic colorectal cancers, which arise on a background of a similar spectrum of mutations to the hereditary cancers. This article examines the genetic mechanisms underlying the hereditary colorectal cancers, as well as genetic predisposition to colorectal cancer in the general population in the absence of a clear-cut genetic syndrome.
Three new mutations in hereditary nonpolyposis colorectal cancer (Lynch syndrome II) in Uruguay
Cancer Genetics and Cytogenetics, 2003
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colorectal cancer (CRC). Our purpose is to describe three extended HNPCC families, each of which manifests novel germline mutations in Uruguay, a small country that is a study model for cancer investigation given its high cancer incidence and mortality rate. This is a study of three extended HNPCC families in which extensive genealogic information, medical history, and pathology findings are critically reviewed. DNA testing was performed for evidence of HNPCC mutations. The findings reveal three novel germline mutations, namely MLH1 , with a deletion resulting in a frameshift and a premature stop codon (codon 228) in one of the families; in the second family, MSH2 exon 1, codon 61 at nucleotide 181, which results in immediate stop of translation; and in the third family, a mutation in MSH2 at exon 3: the amino acid at nucleotide 530, codon 117, causing a frameshift and a premature stop codon eight base pairs later. We conclude that it is important to study HNPCC mismatch repair genes because of emerging evidence for genotypic and phenotypic heterogeneity, which will harbor the potential to eventually translate this knowledge into specific screening and management protocols. Future projections for such mutations could even contribute to the emergence of molecular-based designer drugs developed through advances in genomics, proteomics, high-throughput screening, and bioinformatics, which would be effective therapeutically for these high-cancer risk patients.
HEREDITARY SYNDROMES ASSOCIATED WITH COLORECTAL CANCER (Atena Editora)
HEREDITARY SYNDROMES ASSOCIATED WITH COLORECTAL CANCER (Atena Editora), 2024
Cancer is a condition characterized by disordered and invasive cell growth in the tissues and organs of the human body. Hereditary intestinal cancer affects parts of the large intestine, such as the colon and rectum, and is influenced by hereditary genetic factors, benign lesions and polyps. Colorectal cancer (CRC) is the most common type, with a strong genetic predisposition related to several syndromes, such as familial adenomatous polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Lynch syndrome and Muir syndrome. -Tower. Familial adenomatous polyposis is marked by the formation of numerous polyps in the colon and rectum, increasing the risk of malignancy. Lynch Syndrome, related to mutations in DNA repair genes, increases the incidence not only of colorectal cancer, but also of other types, such as endometrium, ovary and stomach, standing out in the understanding and management of the genetic risk of CRC.