Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A common inherited RFLP of the L-myc proto-oncogene has been reported to correlate with cancer susceptibility or prognosis for some tumors. Using a PCR-based RFLP assay on DNA extracted from peripheral blood samples, we determined the L-myc EcoRI genotype of patients with HCC, patients with other liver tumors, and healthy controls. In this polymorphism there are 2 alleles, L and S, which define 3 possible genotypes: LL, LS, and SS. While the genotype distribution of patients with other liver tumors and healthy controls do not differ from one another, both differ significantly from the genotype distribution of patients with HCC. This difference is primarily the result of a low frequency of the SS genotype among HCC patients compared to controls or other liver tumor patients. Persons with the SS genotype appear to be protected against HCC and have roughly one-ninth the risk of persons who carry one or more copies of the L allele. Within HCC cases, patients with different L-myc genotypes show slight, but not statistically significant, differences in tumor characteristics and survival.
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PMID:L-myc proto-oncogene alleles and susceptibility to hepatocellular carcinoma. 839 82

Cancer is a multistep disease with a multifactorial aetiology. Among the avoidable causes of human cancer are exposure to environmental carcinogens, ionizing and non-ionizing radiation, chronic inflammatory states (viruses and parasites) and life style factors, in particular diet. There is increasing evidence that these aetiologic factors may interact with each other resulting in a more than additive cancer risk. This has been demonstrated for example with hepatitis B virus and aflatoxins in hepatocellular carcinoma and alcohol and tobacco in cancer of the esophagus. The integration of molecular markers of exposure, biological effect and individual susceptibility into epidemiological studies can contribute to strengthening the causal link between exposure and disease and thus help assess the relative contribution of multiple risk factors to the aetiology of a specific cancer. For some genotoxic carcinogens the sequence of events leading to tumour formation is well understood from exposure, to metabolism and ultimately to specific mutations in transformation-associated genes. The mechanisms of action of carcinogens which do not interact directly with DNA but exert adverse effects through receptor-mediated modulation of intercellular signal pathways is far less well understood and an example of this is the interaction between diet and hormones. Furthermore, there is increasing awareness that individual response to environmental agents may depend to a significant extent on the genetic background of the individual or population. This has long been known from animal experiments but human cancer susceptibility is a complex genetic trait involving genes responsible for carcinogen metabolism, DNA repair and as yet unidentified cell specific susceptibility genes. Phenotypic changes observed during tumour progression reflect the sequential acquisition of genetic alterations. To assess the contribution of mutations in the various genes involved in the carcinogenic process may require their expression in transgenic animals or knock out mice. This has again placed animal experimentation into the forefront of mainstream cancer research.
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PMID:Etiology of cancer in humans and animals. 867 81

We have cloned a cDNA from chromosome band 17p13.3, designated as HCAP1 (HCC-associated protein 1, originally named HC56). Database searches revealed that HCAP1 shares most of its open reading frame with GEMIN4. Single nucleotide polymorphism (SNP) screening revealed a high incidence of SNP in the coding region of HCAP1 (12 SNP sites). A collection of 140 controls and 22 cases from the Qidong area was genotyped at 6 SNP sites. The 22 cases exhibited higher frequencies of minor alleles than did the controls, and 2 sites revealed significant differences between the controls and the cases. We constructed 2 haplotypes, HCAP1-N (with common alleles at 5 SNP sites) and HCAP1-M (with minor alleles at 5 SNP sites), in a mammalian expression system. Both haplotypes resulted in a remarkable reduction in colony formation and suppression of cell growth after being transfected into the human hepatocellular carcinoma (HCC) cell line. The inhibitory effect of HCAP1-N was stronger than that of HCAP1-M. Different haplotypes also resulted in different gene expression profiles in the Hep3B cell line according to an examination of 588 genes on an Atlas membrane. The expression induced by HCAP1-M caused an up-regulation of genes involved in cellular proliferation and a down-regulation of genes involved in cellular apoptosis and DNA repair. These results, in addition to the statistical data, are biological evidence that the HCAP1-M variant of HCAP1 has a reduced inhibitory effect on hepatocarcinoma cell growth and an impaired DNA repair system. This suggests that HCAP1-M may be related to cancer susceptibility.
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PMID:Two variants of the human hepatocellular carcinoma-associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B. 1460 41

The C3H/HeJ (C3H) and CBA/J (CBA) mouse strains are classical mouse models of cancer susceptibility, exhibiting high risks for both spontaneous and chemically induced liver cancer. By analysis of backcrosses and intercrosses between C3H or CBA and resistant B6 mice, we have mapped a potent modifier of hepatocellular carcinoma development to distal chromosome 1, linked to the marker D1Mit33 with combined LOD(W) scores of approximately 5.9 (C3H) and 6.5 (CBA). We previously identified this region as one of two that modify susceptibility in the more distantly related C57BR/cdJ (BR) strain. Congenic B6.C3H(D1Mit5-D1Mit17) and B6.BR(D1Mit5-D1Mit17) mice developed significantly more liver tumors than B6 mice did (6- to 13-fold, P < 10(-11), in males; 3- to 4-fold, P < 10(-3), in females). Thus, distal chromosome 1 carries one or more genes that are sufficient to confer susceptibility to liver cancer.
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PMID:A potent modifier of liver cancer risk on distal mouse chromosome 1: linkage analysis and characterization of congenic lines. 1523 34

Age is the major risk factor for cancer, but few genetic pathways that modify cancer incidence during aging have been described. Bin1 is a prototypic member of the BAR adapter gene family that functions in vesicle dynamics and nuclear processes. Bin1 limits oncogenesis and is often attenuated in human cancers, but its role in cancer suppression has yet to be evaluated fully in vivo. In the mouse, homozygous deletion of Bin1 causes developmental lethality, so to assess this role, we examined cancer incidence in mosaic null mice generated by a modified Cre-lox technology. During study of these animals, one notable phenotype was an extended period of female fecundity during aging, with mosaic null animals retaining reproductive capability until the age of 17.3 +/- 1.1 months. Through 1 year of age, cancer incidence was unaffected by Bin1 ablation; however, by 18 to 20 months of age, approximately 50% of mosaic mice presented with lung adenocarcinoma and approximately 10% with hepatocarcinoma. Aging mosaic mice also displayed a higher incidence of inflammation and/or premalignant lesions, especially in the heart and prostate. In mice where colon tumors were initiated by a ras-activating carcinogen, Bin1 ablation facilitated progression to more aggressive invasive status. In cases of human lung and colon cancers, immunohistochemical analyses evidenced frequent attenuation of Bin1 expression, paralleling observations in other solid tumors. Taken together, our findings highlight an important role for Bin1 as a negative modifier of inflammation and cancer susceptibility during aging.
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PMID:Bin1 ablation increases susceptibility to cancer during aging, particularly lung cancer. 1769 64

Adhesion molecules are essential for a wide range of biological and physiological functions, including cell-cell interactions, cell interactions with the extracellular matrix, cell migration, proliferation and survival. Defects in cell adhesion have been associated with pathological conditions such as neoplasia, and neurodegenerative diseases. We have identified a new adhesion molecule of the immunoglobulin family, GlialCAM. The same protein was recently published under the name hepaCAM and was suggested to be associated with hepatocellular carcinoma. Here we have expressed and purified the extracellular domain of this molecule in two mammalian expression systems, HEK and CHO cells. A three step purification protocol gave an over 95% pure protein. The extracellular domain of GlialCAM possesses several potential N- and O-glycosylation sites. Glycosylation is one of the most common post-translational modifications of secreted proteins and of the extracellular domains of membrane bound proteins. It can influence both the activity and the stability of the protein. The glycosylation pattern has been shown to depend on the cell type where the protein is expressed. We examined if differences in the glycosylation of this protein could be detected when it was expressed in the two commonly used mammalian expression systems, HEK and CHO. Differences in the glycosylation were detected.
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PMID:Purification of the extracellular domain of the membrane protein GlialCAM expressed in HEK and CHO cells and comparison of the glycosylation. 1808 21

Previously, we reported the identification of a novel immunoglobulin-like cell adhesion molecule hepaCAM that is frequently downregulated and inhibits cell growth in hepatocellular carcinoma. In this study, we show that the expression of hepaCAM is suppressed in diverse human cancers. Aiming to evaluate the biological role of hepaCAM in breast cancer, we stably transfected the MCF7 cell line with either wild-type hepaCAM or its mutant hCAM-tailless that lacked the cytoplasmic domain. We found that hepaCAM inhibited colony formation and cell proliferation and arrested cells in the G(2)/M phase. Intriguingly, hepaCAM was capable of inducing cellular senescence as defined by the enlarged cell morphology and increased beta-galactosidase activity. Furthermore, hepaCAM elevated the expression levels of senescence-associated proteins including p53, p21 and p27. In contrast, cell growth inhibition and senescence were less apparent in cells overexpressing hCAM-tailless mutant. To determine if the p53-mediated pathway was involved in hepaCAM-induced senescence, we used the small-interfering RNA system to knock down endogenous p53 expression. In the presence of hepaCAM, downregulation of p53 resulted in a clear reduction of p21, insignificant change in p27 and alleviated senescence. Together, the results suggest that the expression of hepaCAM in MCF7 cells not only inhibits cell growth but also induces cellular senescence through the p53/21 pathway.
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PMID:Expression of hepaCAM is downregulated in cancers and induces senescence-like growth arrest via a p53/p21-dependent pathway in human breast cancer cells. 1884 60

EGF promoter polymorphisms are observed to modulate EGF levels and thought to have effect on susceptibility to various carcinomas but the results are inconsistent. In this meta-analysis, we assessed published studies of the association between three EGF polymorphisms and cancer risk from 21 studies with 14,609 subjects for EGF G61A, from two studies with 2,535 subjects for G-1380A and A-1744G, respectively. For EGF G61A, the contrast of homozygote (OR=0.80, 95% CI=0.65-0.98), allele (OR=0.90, 95% CI=0.81-0.99) and dominant model (OR=0.86, 95% CI=0.74-0.99) produced significant association among 21 studies with relatively large heterogeneity (Pheterogeneity<0.001). Through the stratified analysis, heterogeneity decreased significantly. In the stratified analysis by racial descent, the significant risks were found among Asians for homozygote contrast (OR=0.83, 95% CI=0.69-0.99, Pheterogeneity=0.506) and Americans for the contrast of homozygote (OR=0.50, 95% CI=0.30-0.84, Pheterogeneity=0.051), allele (OR=0.70, 95% CI=0.51-0.96, Pheterogeneity=0.008) and dominant model (OR=0.57, 95% CI=0.42-0.77, Pheterogeneity=0.28). No significant associations were found in all Caucasians genetic models. In the subgroup analyses by cancer types, for gastric cancer and esophageal cancer significant associations were found in all genetic models without heterogeneity. Significant risk was also found in the contrast of homozygote (OR=0.41, 95% CI=0.20-0.81, Pheterogeneity=0.184) and recessive model (OR=0.53, 95% CI=0.33-0.85, Pheterogeneity=0.384) for hepatoma and recessive model (OR=0.72, 95% CI=0.53-0.99, Pheterogeneity=0.474) for glioma. For EGF G-1380A and A-1744G, no significant associations were found in all genetic models. This meta-analysis suggests that the EGF G61A polymorphism most likely contributes to decreased susceptibility to cancers among Asians and Americans, and A allele may be a protective factor for gastric cancer, esophageal cancer, hepatoma and glioma. Both EGF G-1380A and A-1744G is marginally associated with cancer susceptibility.
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PMID:Association between EGF promoter polymorphisms and cancer risk: a meta-analysis. 2003 94

Accumulated evidence suggested that cytotoxic T-lymphocyte antigen 4 (CTLA4) plays an important role in the negative regulation of T-cell proliferation and activation, and thus participates in antitumor immunity and cancer surveillance. Previously we reported that the CTLA4 49A/G (rs231775) single nucleotide polymorphism (SNP) was a candidate cancer susceptibility marker for breast, lung, esophageal, and gastric cancers. In the present study, we expanded our study to two infection-related cancers, namely, hepatocellular carcinoma (HCC) and cervical cancer. We genotyped rs231775 in two independent case-control studies of 864 HCC patients and 864 control subjects, and 719 cervical cancer patients and 719 control subjects. In the multivariate logistic regression models, CTLA4 +49 A/G variant genotype was associated with increased risk (AA vs GG) by 1.43-fold (95% CI = 0.94-2.17) for HCC, and 1.66-fold (95% CI = 1.13-2.44) for cervical cancer. Taken together, the results suggest that CTLA4 rs231775 may serve as a common cancer susceptibility marker.
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PMID:CTLA-4 gene polymorphism +49 A/G contributes to genetic susceptibility to two infection-related cancers-hepatocellular carcinoma and cervical cancer. 2053 28

Arg72Pro is a common polymorphism in TP53, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of Arg72Pro in cancer, although the results are conflicting and heterogeneous. Here, we analyzed pooled data from case-control studies to determine the role of Arg72Pro in different cancer sites. We performed a systematic review and meta-analysis of 302 case-control studies that analyzed Arg72Pro in cancer susceptibility. Odds ratios were estimated for different tumor sites using distinct genetic models, and the heterogeneity between studies was explored using I(2) values and meta-regression. We adopted quality criteria to classify the studies. Subgroup analyses were done for tumor sites according to ethnicity, histological, and anatomical sites. Results indicated that Arg72Pro is associated with higher susceptibility to cancer in some tumor sites, mainly hepatocarcinoma. For some tumor sites, quality of studies was associated with the size of genetic association, mainly in cervical, head and neck, gastric, and lung cancer. However, study quality did not explain the observed heterogeneity substantially. Meta-regression showed that ethnicity, allelic frequency and genotyping method were responsible for a substantial part of the heterogeneity observed. Our results suggest ethnicity and histological and anatomical sites may modulate the penetrance of Arg72Pro in cancer susceptibility. This meta-analysis denotes the importance for more studies with good quality and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of Arg72Pro in cancer.
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PMID:Arg72Pro TP53 polymorphism and cancer susceptibility: a comprehensive meta-analysis of 302 case-control studies. 2088 96


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