The genetics of hereditary colon cancer

Abstract

The genetic basis of sporadic colorectal cancer has illuminated our knowledge of human cancer genetics. This has been facilitated and catalyzed by an appreciation and deep understanding of the forms of colorectal cancer that harbor an inherited predisposition, including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, the hamartomatous polyposis syndromes, and certain other rare syndromes. Identification of germline mutations in pivotal genes underlying the inherited forms of colorectal cancer has yielded many dividends, including functional dissection of critical molecular pathways that have been revealed to be important in development, cellular homeostasis, and cancer; new approaches in chemoprevention, molecular diagnostics and genetic testing, and therapy; and underscoring genotypic-phenotypic relationships.

Influence of miRNA-106b and miRNA-135a on butyrate-regulated expression of p21 and Cyclin D2 in human colon adenoma cells

“…It is estimated that 15-30 % of CRC cases exhibit a hereditary influence (Taylor et al 2010). The familial adenomatous polyposis (FAP), for example, is caused by a mutation in the adenomatous polyposis coli (APC) tumor suppressor gene, whereas a mutation in one of the DNA mismatch repair genes is related to hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome) (Rustgi 2007). These hereditary CRC forms as well as closely related variants comprise \5 % of all cancer cases (Fearon 2011;Taylor et al 2010).…”

CLC and IFNAR1 are differentially expressed and a global immunity score is distinct between early- and late-onset colorectal cancer

“…1 The fraction of patients assumed to have an increased genetic risk accounts for 20-30% of all CRC cases, and early onset of disease is one indication of genetic predisposition. 2 However, less than 5% of the cases can be ascribed to known hereditary cancer syndromes, such as familial adenomatous polyposis and Lynch syndrome, with germline mutations in high-penetrance genes (APC and DNA mismatch-repair genes, respectively). 3 Different strategies such as genetic linkage analysis, 4 DNA copy-number analysis, 5 gene expression analysis 6 and genome-wide association studies have been used to identify genetic factors that may predispose patients to cancer.…”

Discovery and validation of colonic tumor-associated proteins via metabolic labeling and stable isotopic dilution

“…Min mice develop tumors in the colon and small intestine and are moribund within 4 months of birth. Loss of APC function in humans causes familial adenomatous polyposis, a rare genetic form of colon cancer (6). More generally, the APC gene is the most frequently mutated gene in a genome-wide survey of spontaneous human colonic tumors (7).…”