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

Fecapentaenes are strong fecal mutagenic compounds presumably occurring in the majority of Western human individuals, and are possibly essential initiators of colon carcinogenesis. Dietary factors have been shown to influence colorectal cancer risk and to modulate both fecal mutagenicity and fecapentaene concentrations. Therefore, in this study, excretion of fecapentaenes is determined in humans consuming either vegetarian or omnivorous diets. The results show that the most predominant fecapentaene forms are excreted in higher concentrations by vegetarians. Consumption of cereal fiber, calcium and carotene as well as fecal concentrations of iso-lithocholic acid were found to correlate positively with excreted concentrations of one or more fecapentaene analogues. On average, 22% of excreted fecapentaene concentrations was found to be related to nutrient intake in stepwise regression models. Dietary calcium intake was found to be the most significant factor positively correlating with excreted fecapentaene concentrations. Intake of mono-unsaturated fatty acids or fiber from vegetables and fruit could be shown to correlate with fecapentaene excretion to a lesser degree. Despite high fecapentaene concentrations in fecal dichloromethane extracts, only 1 out of 20 samples revealed significant mutagenic activity in Salmonella typhimurium TA 100. Further, aqueous extracts of feces from omnivores appeared to be equally mutagenic as feces from vegetarians and contained non-detectable concentrations of fecapentaenes. It is concluded that dietary factors do affect excreted fecapentaene levels, but only to a relatively minor extent. Since vegetarians at low risk for colorectal cancer excrete higher concentrations of fecapentaenes, it could be hypothesized that relatively increased fecapentaene excretion in combination with antimutagenic compounds in feces represents colon cancer prevention.
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PMID:Fecapentaene excretion and fecal mutagenicity in relation to nutrient intake and fecal parameters in humans on omnivorous and vegetarian diets. 154 Sep 28

Cancer is caused by the malfunction of genes that regulate cell proliferation. Two kinds of regulatory genes have been discovered in the search for cancer genes: those that promote growth, called oncogenes, and those that suppress growth, called anti-oncogenes or cancer suppressor genes. The retroviruses that cause animal cancers contain oncogenes coding for growth-promoting signals. These retroviruses rarely cause human cancer but study of their oncogenes has allowed identification of many human cancer genes. These genes code for growth factors, growth factor receptors, cytoplasmic proteins, and nuclear proteins. The complete sequence of cellular growth control begins when a growth factor binds to its receptor and acts directly or indirectly through a G protein and second messenger to induce phosphorylation (activation) of an intracellular protein that ultimately alters the expression of the genes necessary to initiate cell division. At each step in the complex sequence that up-regulates cell division, there is an opposite down-regulating activity produced by the protein products of anti-oncogenes or cancer suppressor genes. These proteins do this by binding to and inactivating transcription factors that initiate DNA synthesis or by directly inactivating the molecules activated by the oncogene products. When this carefully orchestrated and regulated cell control process goes awry because one or more of the proteins in the sequence has been altered by a mutated gene, the cell divides in an uncontrolled manner and malignancy results. It is thought that most human cancers result from a combination of genetic changes that must include both the absence of the protein products of cancer suppressor genes and the presence of abnormal products of oncogenes. The work of Volgelstein and coworkers at Johns Hopkins University has provided the best insight so far into the complex pathogenesis of a common tumor, colon cancer. Carcinogenesis in colon cancer requires a sequence of events that involves more than five genes. Understanding of these pathogenic mechanisms should improve cancer diagnosis and treatment.
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PMID:Oncogenes and cancer suppressor genes. 154 17

Molecules of the cadherin and integrin families involved in cell-cell and cell-matrix adhesion have been implicated in epithelial differentiation, carcinogenesis and metastasis. Having observed that a colon cancer cell line bound avidly to collagen type I, inducing integrin-triggered glandular differentiation, we investigated the regulation of integrin function in these cells. We modified a mammalian expression cloning system that used monoclonal antibody selection to clone cell surface molecules. Using attachment to collagen type I to select for adhesive phenotype, we isolated a complementary DNA clone that increases cell adhesion to components of the extracellular matrix. The corresponding gene (cell adhesion regulator, CAR) is located on the long arm of chromosome 16 (16q) and encodes a protein of 142 amino acids, which has an N-terminal myristoylation motif and a consensus tyrosine-kinase phosphorylation site at the C terminus. Removal of this tyrosine residue abolishes enhancement of cell-matrix adhesion. This gene may encode an adhesion signal transduction molecule that functions in the suppression of tumour invasion.
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PMID:Cloning and characterization of a gene that regulates cell adhesion. 842 14

Aberrant crypt foci represent the earliest detectable lesions of colon cancer. The expression of c-fos in these aberrant crypts was determined by in situ hybridization and immunohistochemistry. These lesions were induced in the colonic epithelium with azoxymethane using the rat model system. Expression of c-fos was markedly increased in the aberrant colonic crypts. Increases of approximately 60 and approximately 70% in the proportion of epithelial cells labelled were observed in the early and advanced aberrant crypts respectively. This was found to be statistically significant (P less than 0.001). Consistent with cell proliferation patterns in the colonic crypts, the epithelial cells of the lower crypt had greater levels of c-fos mRNA than those of the upper part of the crypts. In addition, immunohistochemical staining with c-fos polyclonal antibodies demonstrated increased levels of c-fos protein in aberrant crypts. This combined approach using in situ hybridization and immunohistochemistry has shown that increased c-fos expression at the RNA level in these lesions is associated with increased amounts of c-fos protein. Since c-fos has been implicated in the process of cell proliferation and differentiation, modifications in its expression may be significant to understanding the mechanisms whereby preneoplastic lesions transform to neoplastic lesions in colon cancer.
Carcinogenesis 1992 Apr
PMID:Colonic aberrant crypt foci are associated with increased expression of c-fos: the possible role of modified c-fos expression in preneoplastic lesions in colon cancer. 157 9

Our previous studies have shown that dietary piroxicam, a non-steroidal anti-inflammatory drug (NSAID), and D,L-alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, act as potential chemopreventive agents in inhibiting azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. The present study was designed to determine the effect of these chemopreventive agents on intermediate biomarkers, namely colonic epithelial cell proliferation and levels of prostaglandins, which can be used as effective predictors of colon cancer. Starting at 6 weeks of age, groups of animals were fed the control diet and experimental diets containing piroxicam or DFMO. At 7 weeks of age, all animals, except the vehicle controls, were injected s.c. with AOM at a dose level of 15 mg/kg body wt/week for 4 weeks. Vehicle controls received an equal volume of normal saline. Groups of animals were then killed at the end of last AOM or saline injection (baseline) and at week 4, 16, 24 and 32 following the last AOM or saline treatment. Animals intended for cell proliferation study were injected with bromodeoxyuridine (BrdU) at a dose level of 20 mg/kg body wt 1 h prior to being killed. The rate of colonic cell proliferation at all time points was assessed immunohistochemically using anti-BrdU. The levels of colonic mucosal prostaglandins were estimated by radioimmunoassay. The results indicate that carcinogen treatment increased the colonic cell proliferation measured as the crypt labeling index in proximal and distal colons and the concentrations of colonic prostaglandin E2 (PGE2) and 6-keto PGF1 alpha. The data demonstrate that DFMO significantly inhibited the AOM-induced labeling index in the distal and proximal colon at all time points, whereas piroxicam slightly decreased the labeling index. On the other hand, piroxicam exerted a pronounced inhibitory effect on the levels of both PGE2 and 6-keto PGF1 alpha. DFMO suppressed the colonic PGE2 levels to a lesser degree than piroxicam. The results demonstrate that DFMO, an inhibitor of ODC, suppresses cell proliferation, whereas piroxicam, a NSAID, inhibits prostaglandins, and emphasize the need to develop agent-dependent intermediate biomarker(s) to validate the efficacy of chemopreventive agent(s) in colon carcinogenesis.
Carcinogenesis 1992 Jun
PMID:Effect of the chemopreventive agents piroxicam and D,L-alpha-difluoromethylornithine on intermediate biomarkers of colon carcinogenesis. 160 Jun 22

To investigate an association between colon cancer and obesity during early adulthood--a potentially important period in the etiology of this disease--the authors assembled, by computer linkage, a population-based historical cohort of 52,539 men born between 1913 and 1927 residing in Hawaii (USA), for whom weight and height had been recorded in 1942-43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 737 incident cases of colorectal cancer for 1972-86. An average of 3.8 cancer-free controls were matched to each case on month and year of birth and ethnicity of the parents. A case-control analysis in each anatomic subsite of the large bowel revealed that both early and middle-age body mass increased the risk of sigmoid cancer in men in a dose-dependent fashion. The odds ratios (OR) for sigmoid cancer for the highest compared with the lowest tertiles of Quetelet index were: 2.1 (95 percent confidence interval [CI] = 1.4-3.2) and 1.7 (CI = 1.1-2.5), at ages 15-29 and in prediagnostic years, respectively. These associations were additive and independent of socioeconomic status. Men who were above the median Quetelet index in 1942 and 1972 had an OR of 2.7 (CI = 1.8-4.0), compared with those who were below the median in both periods. This study provides further evidence for an association of obesity with colon cancer in men and suggests that this association is limited to the sigmoid colon and may be related to both early and late events of colon carcinogenesis.
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PMID:Obesity in youth and middle age and risk of colorectal cancer in men. 161 22

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.
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PMID:Evidence that the MCC-APC gene region in 5q21 is not the site for susceptibility to hereditary nonpolyposis colorectal carcinoma. 164 45

In 1971, Denis Burkitt put forward his now famous hypothesis of a fibre-depleted aetiology for colorectal cancer. This was based on his careful clinical observations of the difference in patterns of diseases between Western and traditional African societies. He noted the rarity of colorectal cancer in African countries compared to the West and found that African diets were generally higher in dietary fibre and lower in refined carbohydrates. Since these pioneering observations there have been numerous epidemiological studies but many have failed to support Burkitt's attractive hypothesis. The purpose of this review is to examine the role of dietary fibre in the animal model of colon cancer and to assess critically the findings in the light of current knowledge of the theory of carcinogenesis. The findings from the studies of the experimental model of colon cancer did not support the theory of a fibre-depleted diet as a causative factor in the aetiology of colorectal cancer in man. However, the experimental evidence did suggest that an increase in dietary fibre does have a role in protection from this disease. It was concluded that in colorectal cancer, the effect of a fibre-depleted diet was through a mechanism of promotion (co-carcinogenesis) and that the protective effect of a high fibre diet was by an anticarcinogenic mechanism.
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PMID:Is there a fibre-depleted aetiology for colorectal cancer? Experimental evidence. 165 29

The concept of multistage carcinogenesis is one of the central dogmas of cancer research today. Recent laboratory work suggests that many specific genetic changes are associated with carcinogenesis. At the same time, there is increasing evidence that cell proliferation kinetics are important in carcinogenesis. In 1971, Knudson proposed his now celebrated two-mutation model for embryonal tumors. In fact, a two-mutation model that explicitly considers cell kinetics is the most parsimonious model consistent with the incidence of both childhood and adult cancer in human populations. This model has been known to be consistent, as well, with other epidemiologic and experimental data. But can such a model be reconciled with the laboratory evidence suggesting that many genetic alterations are required for malignant transformation? In this paper, I examine multistage carcinogenesis from the population perspective. Can cancer incidence data in populations provide some insight into the number and nature of stages involved in malignant transformation? I focus attention on carcinoma of the colon because of the considerable amount of information that is now available on the genetics of these tumors. Also, as is the case with retinoblastoma, colon cancer occurs in sporadic and dominantly inherited forms. A comparison of the incidence of these two forms of colon cancer suggests that mutation at the familial adenomatous polyposis (FAP) locus is not necessary for colon cancer, and that inheritance of the gene for FAP is not equivalent to inheriting one of the essential steps on the pathway to colon cancer. Thus, colon cancer does not follow the retinoblastoma paradigm. The incidence of colon cancer in the general population and among polyposis subjects is consistent with two or three mutations on the pathway to malignancy. A three-mutation model is more consistent with the genetic alterations observed in colon carcinogenesis. I present and discuss a working model for colon cancer.
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PMID:A population perspective on multistage carcinogenesis. 166 93

The inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid against colon carcinogenesis was investigated in rats. Four groups of 26 F344 rats each received an intrarectal dose of 2 mg of N-methyl-N-nitrosourea 3 times a week for 2 weeks, and received a diet containing 12% perilla oil, 6% or 12% safflower oil (rich in the n-6 polyunsaturated fatty acid linoleic acid), or 12% palm oil (rich in saturated and monounsaturated fatty acids). At week 35, the incidence of colon cancer was significantly lower in perilla oil-fed rats than in other dietary groups; 19% vs. 46%, 56% and 58%. When examined at week 10, the concentration of fecal bile acids, known to be tumor promoters, was not significantly different among the dietary groups, and the intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity, a marker of tumor promotion, was significantly lower in perilla oil-fed group than in other groups. The serum and colonic mucosal fatty acid compositions and the blood plasma prostaglandin E2 level directly reflected the fatty acid composition of each dietary fat. The results suggest that the anti-tumor-promoting effect of dietary perilla oil was a result of a decreased sensitivity of colonic mucosa to tumor promoters arising from the altered fatty acid composition in membrane phospholipid of colonic epithelial cells, and was not a consequence of a decrease of promoters such as bile acids.
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PMID:Inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid on colon carcinogenesis in rats. 168 47


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