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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Involvement of diet and nutrition as risk factors for human cancers has been established by two general types of evidence. Epidemiological studies in human populations have identified associations between patterns of incidence for various forms of cancer and diet composition or food consumption patterns. Such associations are particularly evident in studies on migrant populations and in patterns of geographic localization of specific forms of cancer. Reduction in gastric cancer (and increase in colon cancer) incidence has been observed in immigrants from Japan to the U.S. via Hawaii with concurrent change in dietary habits. High fat consumption has been linked to increased incidence of breast and colon cancer, and evidence is accumulating that suggests increased intake of dietary fiber (or some specific component of it) may be associated with diminished risk of colorectal cancer. Laboratory studies have demonstrated the existence of dietary constituents that might impact cancer risk in people consuming them. Substances in this class fall into two general categories: genotoxic carcinogens/mutagens; and protective factors which inhibit experimentally-induced chemical carcinogenesis in animals. Numerous naturally-occurring carcinogens/mutagens have been identified. Examples include aflatoxins, cycasin, and bracken fern carcinogen(s), among others. Genotoxic substances associated with the use of intentional food additives are the N-nitroso compounds formed as nitrosation products from nitrite. Potential carcinogenic risk from food constituents also comes from mutagens found in foods as natural components, or formed in the course of cooking.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diet and nutrition as risk factors for cancer. 302 65

Historically, the field of experimental chemical carcinogenesis began in Japan with Yamagiwa and has been a traditional subject of study since that time. In Prof. Nakahara's lifetime, he and his disciples have contributed much to an understanding of the basic mechanisms of carcinogenesis. Most types of human cancer are likely associated with chemical carcinogens. In part, we understand the mechanisms whereby carcinogens lead to neoplasia. The overall process involves agents with distinct properties, 1) those modifying the genome with specific consequences, and 2) those controlling the growth and development of latent tumor cells with such an abnormal genome. The genotoxic pathway and the subsequent promoting process proceed by distinct mechanisms and thus have different consequences as regards health risk, especially with respect to dosage and time requirements for effective carcinogenesis. Through multidisciplinary approaches, it has been established that cancer of the stomach and esophagus, prevalent in certain parts of the world, depend on the presence in salted, pickled, or smoked foods of specific chemicals, that are genotoxic and the structure of which is a function of local conditions. Salt can have a cocarcinogenic or promoting role. In much of the Western World, cancers of the colon, pancreas, breast, ovary, endometrium, and prostate are linked to nutritional traditions. The genotoxic carcinogens for several of these neoplasms may be formed during cooking, especially broiling or frying. There is evidence for extensive promoting process, in turn, a function of the total dietary fat intake, through partially understood mechanisms. Additional modifying factors include cereal (bran) fiber, but perhaps not other types of fibers, that reduce the risk for colon cancer. Further modifying elements are discussed in this Symposium. Fair understanding has been achieved of the underlying basic mechanisms, relative to the formation of carcinogens during food preparation and processing, and on the role of certain promoting or inhibiting elements such as fat, fiber, or components of fruits and vegetables. Certain of these elements are sufficiently well established for application to the prevention of specific cancers in various parts of the world.
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PMID:Nakahara memorial lecture. Application of the mechanisms of nutritional carcinogenesis to the prevention of cancer. 391 90

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.
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PMID:Biologic markers in cancer diagnosis and treatment. 702 76

Colon cancer is one of the most frequent causes of cancer death in western countries. Epidemiological studies suggest that colorectal cancer can be attributed, at least in part, to carcinogens and mutagens present in the diet and/or the environment. The covalent binding of these xenobiotics or their reactive metabolites to DNA is believed to initiate this chemical carcinogenesis. In the present study, using a 32P-postlabeling method, we investigated DNA adduct levels in control colons from patients without colorectal adenocarcinoma and in nontumoral and tumoral tissues from patients with colorectal adenocarcinoma. Our results show that the DNA adduct level is significantly higher (P < 0.001) in nontumoral than in control or tumoral colon samples. For the first time, we demonstrate in humans that the presence of numerous adducts in colonic mucosa is associated with colorectal cancer, a finding in agreement with the importance of chemical factors in causing this disease; therefore, after confirmation of the link between DNA adducts and colorectal cancer, the measurement of DNA adduct levels in colon samples could constitute a useful approach to the early detection of colorectal cancer.
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PMID:High levels of DNA adducts in human colon are associated with colorectal cancer. 758 42

D-Glucaric acid (GA) is a nontoxic, natural compound. One of its derivatives is the potent beta-glucuronidase inhibitor D-glucaro-1,4-lactone (1,4-GL). The goal of this study was to demonstrate the in vivo formation of 1,4-GL from a D-glucarate salt and determine its metabolism, uptake by selected organs, and excretion following oral administration of potassium hydrogen D-[14C]glucarate to male and female Sprague-Dawley rats. 1,4-GL increases detoxification of carcinogens and tumor promoters/progressors by inhibiting beta-glucuronidase and preventing hydrolysis of their glucuronides. 1,4-GL and its precursors, such as potassium hydrogen D-glucarate and calcium D-glucarate, may exert their anticancer action, in part, through alterations in steroidogenesis accompanied by changes in the hormonal environment and the proliferative status of the target organ. Thus, GA derivatives may be useful as new or adjuvant cancer preventive and therapeutic agents. In our study, 1,4-GL was found to be formed from the D-glucarate salt in the stomach of rats. It was apparently absorbed from the gastrointestinal tract, transported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant differences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from D-glucaric acid derivatives may be prerequisite for their inhibition of chemical carcinogenesis in rodents and prevention of breast, prostate, and colon cancer in humans.
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PMID:Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention. 910 Oct 79

The mechanism by which vitamin A prevents or delays chemical carcinogenesis remains unclear. In addition to these antimutagenic and antiproliferative activities, vitamin A seems able to induce programmed cell death. In this study, we assess the suggested role of vitamin A on the in vitro apoptosis induction in a rat colonic tumor cell line. Several concentrations of retinyl palmitate were added in the culture media. We observed cell proliferation by measuring the (3H)thymidine incorporation, cell differentiation by measuring the intestinal alkaline phosphatase expression, and apoptosis induction by DNA fragmentation and morphological evolution of adherent and floating cells. The results show that vitamin A decreases (3H)thymidine incorporation after 1 day of treatment, induces alkaline phosphatase expression, and increases the number of cells falling in apoptosis. This report confirms the role of vitamin A on the induction of cell differentiation, on the inhibition of cell proliferation and shows the vitamin A capacity to induce apoptosis. These results could be attractive to prevent development of colon cancer by vitamin A supplemented diets.
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PMID:Vitamin A and apoptosis in colonic tumor cells. 928 52

It has become clear that several polymorphisms of human drug-metabolizing enzymes influence an individual's susceptibility for chemical carcinogenesis. This review gives an overview on relevant polymorphisms of four families of drug-metabolizing enzymes. Rapid acetylators (with respect to N-acetyltransferase NAT2) were shown to have an increased risk of colon cancer, but a decreased risk of bladder cancer. In addition an association between a NAT1 variant allele (NAT*10, due to mutations in the polyadenylation site causing approximately two fold higher activity) and colorectal cancer among NAT2 rapid acetylators was observed, suggesting a possible interaction between NAT1 and NAT2. Glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) are polymorphic due to large deletions in the structural gene. Meta-analysis of 12 case-control studies demonstrated a significant association between the homozygous deletion of GSTM1 (GSTM1-0) and lung cancer (odds ratio: 1.41; 95% CI: 1.23-1.61). Combination of GSTM1-0 with two allelic variants of cytochrome P4501A1 (CYP1A1), CYP1A1 m2/m2 and CYP1A1 Val/Val further increases the risk for lung cancer. Indirect mechanisms by which deletion of GSTM1 increases risk for lung cancer may include GSTM1-0 associated decreased expression of GST M3 and increased activity of CYP1A1 and 1A2. Combination of GST M1-0 and NAT2 slow acetylation was associated with markedly increased risk for lung cancer (odds ratio: 7.8; 95% CI: 1.4-78.7). In addition GSTM1-0 is clearly associated with bladder cancer and possibly also with colorectal, hepatocellular, gastric, esophageal (interaction with CYP1A1), head and neck as well as cutaneous cancer. In individuals with the GSTT1-0 genotype more chromosomal aberrations and sister chromatid exchanges (SCEs) were observed after exposure to 1,3-butadiene or various haloalkanes or haloalkenes. Evidence for an association between GSTT1-0 and myelodysplastic syndrome and acute lymphoblastic leukemia has been presented. A polymorphic site of GSTP1 (valine to isoleucine at codon 104) decreases activity to several carcinogenic diol epoxides and was associated with testicular, bladder and lung cancer. Microsomal expoxide hydrolase (mEH) is polymorphic due to amino acid variation at residues 113 and 139. Polymorphic variants of mEH were associated with hepatocellular cancer (His-113 allele), ovarian cancer (Tyr-113 allele) and chronic obstructive pulmonary disease (His-113 allele). Three human sulfotransferases (STs) are regulated by genetic polymorphisms (hDHEAST, hM-PST, TS PST). Since a large number of environmental mutagens are activated by STs an association with human cancer risk might be expected.
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PMID:Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. 1002 93

While calcium D-glucarate was shown to inhibit chemical carcinogenesis in various animal models, the effect of potassium hydrogen D-glucarate has not been extensively investigated. In the present study, potassium hydrogen D-glucarate markedly inhibited azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. Potassium hydrogen D-glucarate (PHG) or potassium hydrogen carbonate (PHC) were administered to rats in a diet (140 mmol/kg). Continual post-initiation treatment with potassium hydrogen D-glucarate reduced both tumor incidence and multiplicity at sacrifice by ca. 60%, while PHC had no effect. amelioration of overexpression of the betaG gene in rat colon carcinomas was observed using RT-PCR and Northern blot analysis. We hypothesize that previously demonstrated conversion of PHG to D-glucaro-1,4-lactone, a potent inhibitor of beta-glucuronidase (betaG), may be responsible for this effect. The mechanism of PHG inhibition of colon carcinogenesis may also involve suppression of cell proliferation and possibly alterations in cholesterol synthesis or cholesterol metabolism to bile acids. In conclusion, PHG possesses excellent potential as a natural, apparently non-toxic inhibitor to prevent colon cancer.
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PMID:Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate. 1060 47

Mutations in the human adenomatous polyposis (APC) gene are causative for familial adenomatous polyposis (FAP), a rare condition in which numerous colonic polyps arise during puberty and, if left untreated, lead to colon cancer. The APC gene is a tumor suppressor that has been termed the "gatekeeper gene" for colon cancer. In addition to the 100% mutation rate in FAP patients, the APC gene is mutated in >80% of sporadic colon and intestinal cancers. The Apc gene in mice has been mutated either by chemical carcinogenesis, resulting in the Min mouse Apcdelta850, or by heterologous recombination, resulting in the Apcdelta716 or Apedelta1368 mice (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). Although homozygote Apc-/- mice are embryonically lethal, the heterozygotes are viable but develop numerous intestinal polyps with loss of Apc heterozygosity within the polyps (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). The proinflammatory, prooncogenic protein cyclooxygenase (COX)-2 has been shown to be markedly induced in the Apcdelta716 polyps at an early stage of polyp development (M. Oshima et al., Cell, 87: 803-809, 1996). We demonstrate here that treatment with the specific COX-2 inhibitor rofecoxib results in a dose-dependent reduction in the number and size of intestinal and colonic polyps in the Apcdelta716 mouse. The plasma concentration of rofecoxib that resulted in a 55% inhibition of polyp number and an 80% inhibition of polyps > 1 mm in size is comparable with the human clinical steady-state concentration of 25 mg rofecoxib (Vioxx) taken once daily (A. Porras et al., Clin. Pharm. Ther., 67: 137, 2000). Polyps from both untreated and rofecoxib- or sulindac-treated Apcdelta716 mice expressed COX-1 and -2, whereas normal epithelium from all mice expressed COX-1 but minimal amounts of COX-2. Polyps from either rofecoxib- or sulindac-treated mice had lower rates of DNA replication, expressed less proangiogenic vascular endothelial-derived growth factor and more membrane-bound beta-catenin, but showed unchanged nuclear localization of this transcription factor. This study showing the inhibition of polyposis in the Apcdelta716 mouse suggests that the specific COX-2 inhibitor rofecoxib (Vioxx) has potential as a chemopreventive agent in human intestinal and colon cancer.
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PMID:Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. 1124 90

The pyruvate kinase isoenzyme M2-PK is known to be associated with a metabolic shift that is characteristic for tumor cells. Meanwhile, the universal expression of this isoenzyme is the basis for the detection of various tumor diseases in human clinical diagnosis. Other enzymes which are known to be essential for this tumor specific metabolic shift in rat chemical carcinogenesis are the NADP-dependent enzymes malic enzyme, isocitrate dehydrogenase and glucose 6-phosphate dehydrogenase. To evaluate the role of these enzymes in human carcinogenesis, we compared their enzymatic activities in normal colon mucosa and tissues derived from primary colon tumors. Histochemical staining showed that the enzyme activities were restricted to mucosal colon cells and colon cancer cells. The enzymes were strongly but heterogeneously expressed in the tumor tissues, whereas staining of normal mucosa was weak. Tumor M2-PK showed the most prominent differences in normal colon mucosa and colon cancer cells.
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PMID:Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. 1132 87


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