Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for familial adenomatous polyposis coli (APC or FAP), which has previously been linked to chromosome 5q21 has been identified. The APC gene has been found to be altered by point mutations in the germ line of both adenomatous polyposis coli and Gardner's syndrome patients and somatically in tumors from sporadic colorectal cancer patients. During the hunt for the APC gene, the closely linked MCC (mutated in colorectal cancer) gene was identified and found to be altered somatically in tumors from sporadic cancer patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal carcinogenesis and that mutations at the APC gene can cause both adenomatous polyposis coli and Gardner's syndrome. The identification of these genes should aid in the counseling of patients with genetic predispositions to colorectal cancer. Progress has also been made in identifying specific genetic changes that occur in other gastrointestinal cancers. A mutational "hotspot" in the p53 gene in human hepatocellular carcinomas has been identified that could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1.
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PMID:Cell and molecular biology of gastrointestinal tract cancer. 132 39

Mutation of the p53 gene and loss of heterozygosity of the p53, Rb, APC, and MCC genes were examined in 14 hepatocellular carcinomas (HCCs) diagnosed at the third department of internal medicine in Asahikawa Medical College. Mutations in the p53 gene were detected in 4 HCCs out of 14 (25%) using polymerase chain reaction-single strand conformational polymorphism. The sites of the mutations showed a random distribution from exon 6 to 8. No mutation was observed at codon 249, which has been considered as a mutational hot spot caused by aflatoxin B1. All of the mutations occurred at a G:C base pair site, while two mutations were C:G to T:A transitions and other two mutations were G:C to T:A transversions. Pathological examination showed that the 14 HCCs consisted of 7 moderately and 7 poorly differentiated HCCs. All of the 4 HCCs which showed mutations were poorly differentiated and the frequency of the mutations were 0% in moderately and 57% in poorly differentiated HCCs. Loss of heterozygosity of the p53, Rb and APC genes were examined in the 14 HCCs using restriction fragment length polymorphism analysis. Frequencies of the loss of the p53, Rb, APC, and MCC genes were 2 out of 7 informative cases (2/7), 1/6, 0/4, and 0/7, respectively. Frequency of loss of the p53 gene in four HCCs carrying a mutated p53 gene was 1/3. These data suggest that inactivation of the p53 gene is involved in human hepatocarcinogenesis, but the APC/MCC genes are not.
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PMID:[Aberrations of tumor suppressor genes in hepatocellular carcinomas]. 786 63

Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas (HCC) from southern Africa and Qidong in China. The objective of the present work was to test the hypothesis that exposure to aflatoxin B1 either alone or coincident with other environmental carcinogens might be associated with allelic losses occurring during development of human hepatocarcinogenesis in China. The HCCs were obtained from two different areas in China: Qidong, where exposure to hepatitis B virus (HBV) and aflatoxin B1 is high; and Beijing, where exposure to HBV is high but that of aflatoxin B1 is low. We analyzed the tumors for mutations in the p53 gene and loss of heterozygosity for the p53, Rb, and APC genes and at marker loci on chromosomes 4, 13, and 16. Frequencies of mutation, loss, and aberration (mutation and loss) of the p53 gene in 25 HCCs from Qidong were 60, 58, and 80%, respectively. The frequencies in 9 HCCs from Beijing were 56, 57, and 78%. However, the frequency of a G to T transversion at codon 249 in HCCs from Qidong and Beijing were 52 and 0%, respectively. These data indicate that mutation and/or loss of heterozygosity in the p53 gene, independent of the 249 mutation, play a critical role in the development of hepatitis B virus-associated HCCs in China. Loss of the Rb and APC genes was observed in 44 and 7% of HCCs from Qidong, respectively. Allelic losses on chromosome 4 and especially on chromosome 16 were frequent in HCCs from Qidong but were not observed in HCCs from Beijing, while loss of heterozygosity on chromosome 13 occurred at similar frequency in both Qidong and Beijing. These results show a distinct difference in the pattern of allelic losses between HCCs in Qidong and Beijing and suggest that aflatoxin B1 and/or other environmental carcinogens may contribute to this difference.
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PMID:Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China. 806 70

The susceptibility of an individual to oral cancer is mediated by genetic factors and carcinogen-exposure behaviors such as betel quid chewing, tobacco use, and alcohol consumption. This pilot study was aimed to identify the genetic alteration in 100 bp upstream and downstream flanking regions in addition to the exonic regions of 169 cancer-associated genes by using Next Generation sequencing with aim to elucidate the molecular pathogenesis of tobacco- and betel quid-associated oral cancer of Northeast India. To understand the role of chemical compounds present in tobacco and betel quid associated with the progression of oral cancer, single nucleotide polymorphisms (SNPs) and insertion and deletion (Indels) found in this study were analyzed for their association with chemical compounds found in tobacco and betel quid using Comparative Toxogenomic Database. Genes (AR, BRCA1, IL8, and TP53) with novel SNP were found to be associated with arecoline which is the major component of areca nut. Genes (BARD1, BRCA2, CCND2, IGF1R, MSH6, and RASSF1) with novel deletion and genes (APC, BRMS1, CDK2AP1, CDKN2B, GAS1, IGF1R, and RB1) with novel insertion were found to be associated with aflatoxin B1 which is produced by fermented areca nut. Genes (ADH6, APC, AR, BARD1, BRMS1, CDKN1A, E2F1, FGFR4, FLNC, HRAS, IGF1R, IL12B, IL8, NBL1, STAT5B, and TP53) with novel SNP were found to be associated with aflatoxin B1. Genes (ATM, BRCA1, CDKN1A, EGFR, IL8, and TP53) with novel SNP were found to be associated with tobacco specific nitrosamines.
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PMID:A pilot study evaluating genetic alterations that drive tobacco- and betel quid-associated oral cancer in Northeast India. 2494 87