Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited predisposition to colorectal cancer, which is caused by germline mutations in the adenomatous polyposis coli (APC) gene.
However, the majority of sporadic forms of colorectal cancer are characterized by inactivation of the tumor suppressor gene APC due to loss of heterozygosity (LOH), resulting in deregulation of the protein β-catenin.
In a large cohort of patients with early-onset colorectal cancer, germline TP53 mutations were detected at a frequency comparable with the published prevalence of germline APC mutations in colorectal cancer.
Genes underlying these cancers are now recognized in colorectal cancer (APC, mismatch repair genes, LKB1) and in breast cancer (BRCA1, BRCA2) whereas, in prostate cancer, a locus in chromosome 1 (HPC1) has been proposed on the basis of linkage analysis.
This allele significantly decreased the luciferase reporter's activity CONCLUSION: Our results indicate that many SNPs in APC promoters 1A and 1B are functionally relevant and that allele G of rs79896135 may be associated with the predisposition to colorectal cancer.
We sequenced the entire open reading frame of the APC gene and tested for two common MYH mutations in a population-based series of patients with colorectal cancer and 5 to 99 adenomas.
Furthermore, we found that PGT expression decreased in premalignant adenomas in APC(min) mice and was partially restored (in human colorectal cancer cell lines) by treatment with a DNA demethylating agent or histone deacetylase inhibitor.
These data not only allow use of flanking markers for presymptomatic diagnosis of FAP but also provide a high-density map of the region for isolation of the APC gene itself and for further assessment of the role of chromosome 5 deletions in the biology of sporadic colorectal cancer.
The I1307K allele of the APC gene has been shown to confer a modestly elevated risk of colorectal cancer in the Ashkenazi Jewish population (relative risk, 1.5-1.7).
Familial adenomatous polyposis (FAP) is a dominant inherited colorectal cancer syndrome which is caused by germline mutations in the adenomatous polyposis coli (APC) gene.
This is significant because the spatial dysregulation of [Formula: see text]-catenin by the mutated tumor suppressor gene/protein APC in human colonic crypts is responsible for the initiation and growth of colorectal cancer.
Elevated deoxycholic acid (DCA), mutations in the adenomatous polyposis coli (APC) gene and chronic inflammation are associated with increased risk of colorectal cancer.
IMPLICATIONS: The tumor-suppressive function of APC, the most frequently mutated gene in colorectal cancer, is mainly attributed to its role in β-catenin/Wnt signaling.
Given the significance of APC in colorectal cancer, we investigated the association between common single-nucleotide polymorphisms (SNP) in the APC gene and the odds of developing metachronous colorectal adenomas as a surrogate measure of colorectal cancer risk.