Familial adenomatous polyposis of the colon

Abstract

Familial adenomatous polyposis (FAP) is a well-defined autosomal dominant predisposition to the development of polyposis in the colon and rectum at unusually early ages. The first symptoms of FAP are diarrhea and blood in the stool. Weight loss and weaknesses occur after the development of advanced tumour. The incidence of the FAP disorder is one per 10000 newborns. There are high levels of heterogeneity with regard to the number and timing of the occurrence of polyps. The classical form of FAP is characterized by the presence of more than 100 polyps, which appear in the second decade of life. The average time of occurrence of polyps is 15 years. The earliest symptoms of polyposis have been observed in a three-year-old child. The polyps are characterized by large potential for the development towards malignant tumour. Malignancy can occur from late childhood onwards. Attenuated adenomatous polyposis coli is characterized by a more benign course of disease in contrast to classical FAP. The occurrence of FAP is associated with mutations in the APC tumour suppressor gene, which was described in 1991. The APC gene is located on chromosome 5q21 and is involved in cell proliferation control. A recessive form of adenomatous polyposis is caused by mutations in the base excision repair gene - MUTYH gene. The MUTYH gene is involved in repairing DNA lesions as a result of oxidative DNA damage. MUTYH associated polyposis (MAP) is a predisposition to the development of polyps of the colon but the number of polyps is lower in comparison to classical FAP. The high risks of cancer observed in these two diseases make them important medical issues. Molecular studies of colonic polyposis have been performed in Poland for over fifteen years. A DNA Bank for Polish FAP patients was established at the Institute of Human Genetics in Poznan in which DNA samples from 600 FAP families have been collected.

Identification a nonsense mutation of APC gene in Chinese patients with familial adenomatous polyposis

“…disorders and desmoid tumors (9). APC is a tumor suppressor gene located on the long arm of chromosome 5 in band q21, whose mutation is responsible for CFAP and AFAP.…”

Multistage vector delivery of sulindac and silymarin for prevention of colon cancer

“…This disorder arises from germline mutations in the adenomatous polyposis coli (APC) gene that acts as a tumor suppressor [2]. Patients with this disease eventually develop colorectal cancer and other cancers of the digestive tract, which typically present themselves in the mid-teens [1]. Prophylactic surgery is the current standard of care to prevent malignancy.…”

“…Familiar adenomatous polyposis (FAP) is a genetic condition with a prevalence of one in 10,000 newborns [1]. This disorder arises from germline mutations in the adenomatous polyposis coli (APC) gene that acts as a tumor suppressor [2].…”

Codon-level co-occurrences of germline variants and somatic mutations in cancer are rare but often lead to incorrect variant annotation and underestimated impact prediction

“…SNVs are present even in the coding regions of genes related to cancer—amongst germline mutations gathered from the first phase of the 1000 Genomes Project [1], variants can be detected in more than eighty percent of COSMIC census cancer genes [3]. How these variants contribute on their own to cancer risk and development has long been a topic of interest, from family-based studies to identify rare variants that dramatically increase cancer risk [4–5] to GWAS to identify common SNPs that may modulate disease [6–7]. However, less is known about how inherited germline variants interact with the somatic variants gained during tumor development.…”