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

Colon carcinoma is the most common tumor of the gastrointestinal tract. According to some investigators, insulin, epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) man be involved in the neoplastic proliferation. Insulin-binding and receptor tyrosine kinase activity were investigated in colon carcinomas and in normal colons. The insulin receptor concentration, as shown by binding assays, was 17.4 +/- 4.3 fmol/micrograms in normal colon and 29.69 +/- 9.4 fmol/micrograms in colon carcinoma. Nevertheless, the insulin affinity of the receptor was similar in both groups (Kd identical to 1 nM). Both normal and neoplastic colon showed phosphorylation of the insulin receptor. The electrophoretic migration of the beta-subunit of the insulin receptors purified from colon carcinomas was similar to that of normal colon and both tissues demonstrated an insulin-dependent autophosphorylation. The receptor tyrosine kinase activity was measured by the incorporation of [gamma 32P]ATP into the beta-subunit. The basal and the insulin-stimulated tyrosine kinase activities were significantly higher in colon carcinomas compared to normal colon tissues (2.2 and 1.6 times, respectively). Understanding the metabolism of neoplastic cells may contribute to the development of prevention strategies as well as new therapies. It is now necessary to study other steps of the insulin signal transduction pathway, such as insulin receptor substrate 1 phosphorylation.
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PMID:Insulin receptor tyrosine kinase activity in colon carcinoma. 922 17

It has been hypothesized that levels of triglycerides, glucose, and insulin are associated with risk of colon cancer and that diets high in simple sugars increase risk of colon cancer because of their impact on these factors. Limited epidemiological evidence supports the association between simple carbohydrates and risk of colon cancer. Using data from a population-based case-control study (n = 1993 cases and 2410 controls), we examined the associations between dietary sugars, foods containing high level of sugars, and dietary glycemic index (GI) and colon cancer. A dietary GI was developed to estimate metabolic response to a diet that may increase plasma glucose levels. Dietary data were obtained using a validated diet history questionnaire. High levels of sucrose intake were associated with increased risk of colon cancer among younger men [odds ratio (OR) for highest quintile relative to lowest, 1.59; 95% confidence interval (CI), 1.07-2.37]. There was also a trend of increasing colon cancer risk associated with a higher sucrose:dietary ratio for proximal tumors in both men and women. Individuals with proximal tumors who consumed a diet ranked as having a high GI were at increased risk (for men, comparing highest quintile to lowest quintile: OR, 1.58; 95% CI, 1.06-2.36; P trend 0.04; for women: OR, 1.72; 95% CI, 1.11-2.67; P trend 0.04). Those at greatest risk from a high dietary GI were those who were sedentary (for men, relative to those who were most active and had a low-GI diet: OR, 3.46; 95% CI, 1.78-6.70; for women: OR, 2.00; 95% CI, 0.98-4.07). We also observed that people who had a high sucrose: dietary fiber ration and who also were sedentary and had a large body mass index were at increased risk (OR, 4.58; 95% CI, 2.33-8.98) relative to those who had a low sucrose:dietary fiber ratio, were active, and had low body mass indices. These findings support previous reports that dietary sugars, especially diet high in simple carbohydrates relative to complex carbohydrates, increase risk of colon cancer, possibly through their impact on plasma glucose levels.
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PMID:Dietary sugar and colon cancer. 929 74

McKeown-Eyssen and Giovannucci recently proposed that the etiology of insulin resistance (IR) and colorectal cancer (CRC) are related. They suggested that diets high in fat and energy and low in complex carbohydrates and a sedentary life-style lead to IR and that the associated hyperinsulinemia, hypertriglyceridemia, and glycemia lead to increased CRC risk through the growth-promoting effect of insulin or the increased availability of energy. We reasoned that if diet affects colon carcinogenesis through its effect on IR, evidence of colon cancer promotion would be preceded by evidence of IR. To test this expectation, we compared the effects of a high-fat (HF, 59% energy) diet and a low-fat (LF, 11% energy) diet on indirect measures of IR and promotion in azoxymethane-initiated F344 rats. Promotion was assessed as growth of aberrant crypt foci (ACF) at 100 days after initiation. The HF diet increased ACF size 1.4 times (95% confidence interval = 1.30-1.58) that of the LF diet. The HF diet also led to impaired oral glucose tolerance tests measured at 4, 32, 60, and 88 days and characterized by an average increased glucose concentration of 0.78 +/- 0.17 mmol/l (p < 0.001). It also resulted in an impaired intravenous glucose tolerance test and elevated levels of serum insulin after a glucose gavage. We concluded that with this model a high-fat diet leads to evidence of IR before it is possible to demonstrate CRC promotion, thus providing support, necessary but not sufficient, for the causal hypothesis linking IR and CRC. Possible mechanisms linking diet, IR, and promotion are considered.
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PMID:Insulin resistance and promotion of aberrant crypt foci in the colons of rats on a high-fat diet. 938 87

The relationship between diabetes mellitus and the risk of colorectal cancer was investigated in a multicenter case-control study, conducted in Italy between 1992 and 1996 on 1225 cases of incident, histologically confirmed colon cancer, 728 cases of rectal cancer, and 4154 controls, who were in the hospital for acute, nonneoplastic diseases. Overall, 66 (5.4%) cases of colon cancer, 50 (6.9%) cases of rectal cancer, and 185 (4.4%) controls reported a history of diabetes. The corresponding multivariate odds ratios (ORs) were 1.2 [95% confidence interval (CI), 0.8-1.6] for colon, 1.5 (95% CI, 1.1-2.2) for rectal, and 1.3 (95% CI, 1.0-1.6) for all colorectal cancers. No association was observed for subjects who were diagnosed with diabetes at ages of < 40 years (7 cases and 27 controls, OR = 0.9). The OR was 1.4 (95% CI, 1.1-1.7) for subjects who were diagnosed with diabetes at ages of > or = 40 years and were likely to have non-insulin-dependent diabetes. The association was also stronger (OR = 1.6; 95% CI, 1.1-2.3) among subjects whose diabetes was diagnosed 10 or more years in advance and who were > or = 60 years old at the time of colorectal cancer diagnosis. None of the other covariates, including sex, education, body mass index, physical activity, energy intake, alcohol drinking, and fiber intake, showed any appreciable modifying effect. Thus, this uniquely large case-control study of colorectal cancer confirms that subjects with non-insulin-dependent diabetes mellitus have a slightly increased risk of colorectal cancer. More importantly, allowance for a large number of identified potential confounding factors, including body mass index, diet, and physical activity, could not explain the excess colorectal cancer risk among subjects with diabetes mellitus. These findings have plausible biological correlations because insulin-like-growth factor-I is a promoter of colon tumor cell growth in vitro.
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PMID:Diabetes mellitus and colorectal cancer risk. 941 95

Colorectal cancer is a significant cause of morbidity and mortality in Western populations. This cancer develops as a result of the pathologic transformation of normal colonic epithelium to an adenomatous polyp and ultimately an invasive cancer. The multistep progression requires years and possibly decades and is accompanied by a number of recently characterized genetic alterations. Mutations in two classes of genes, tumor-suppressor genes and proto-oncogenes, are thought to impart a proliferative advantage to cells and contribute to development of the malignant phenotype. Inactivating mutations of both copies (alleles) of the adenomatous polyposis coli (APC) gene--a tumor-suppressor gene on chromosome 5q--mark one of the earliest events in colorectal carcinogenesis. Germline mutation of the APC gene and subsequent somatic mutation of the second APC allele cause the inherited familial adenomatous polyposis syndrome. This syndrome is characterized by the presence of hundreds to thousands of colonic adenomatous polyps. If these polyps are left untreated, colorectal cancer develops. Mutation leading to dysregulation of the K-ras protooncogene is also thought to be an early event in colon cancer formation. Conversely, loss of heterozygosity on the long arm of chromosome 18 (18q) occurs later in the sequence of development from adenoma to carcinoma, and this mutation may predict poor prognosis. Loss of the 18q region is thought to contribute to inactivation of the DCC tumor-suppressor gene. More recent evidence suggests that other tumor-suppressor genes--DPC4 and MADR2 of the transforming growth factor beta (TGF-beta) pathway--also may be inactivated by allelic loss on chromosome 18q. In addition, mutation of the tumor-suppressor gene p53 on chromosome 17p appears to be a late phenomenon in colorectal carcinogenesis. This mutation may allow the growing tumor with multiple genetic alterations to evade cell cycle arrest and apoptosis. Neoplastic progression is probably accompanied by additional, undiscovered genetic events, which are indicated by allelic loss on chromosomes 1q, 4p, 6p, 8p, 9q, and 22q in 25% to 50% of colorectal cancers. Recently, a third class of genes, DNA repair genes, has been implicated in tumorigenesis of colorectal cancer. Study findings suggest that DNA mismatch repair deficiency, due to germline mutation of the hMSH2, hMLH1, hPMS1, or hPMS2 genes, contributes to development of hereditary nonpolyposis colorectal cancer. The majority of tumors in patients with this disease and 10% to 15% of sporadic colon cancers display microsatellite instability, also know as the replication error positive (RER+) phenotype. This molecular marker of DNA mismatch repair deficiency may predict improved patient survival. Mismatch repair deficiency is thought to lead to mutation and inactivation of the genes for type II TGF-beta receptor and insulin-like growth-factor II receptor. Individuals from families at high risk for colorectal cancer (hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis) should be offered genetic counseling, predictive molecular testing, and when indicated, endoscopic surveillance at appropriate intervals. Recent studies have examined colorectal carcinogenesis in the light of other genetic processes. Telomerase activity is present in almost all cancers, including colorectal cancer, but rarely in benign lesions such as adenomatous polyps or normal tissues. Furthermore, genetic alterations that allow transformed colorectal epithelial cells to escape cell cycle arrest or apoptosis also have been recognized. In addition, hypomethylation or hypermethylation of DNA sequences may alter gene expression without nucleic acid mutation.
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PMID:Molecular biology of colorectal cancer. 943 4

To elucidate the influence of diet on colorectal carcinogenesis, 1225 subjects with cancer of the colon, 728 with cancer of the rectum and 4154 controls, hospitalized with acute non-neoplastic diseases, were interviewed between 1992 and 1996 in six Italian areas. The validated food frequency questionnaire included 79 questions on food items and recipes which were grouped into 16 food groups. After allowing for nondietary confounding factors and total energy intake, a significant trend towards an increasing risk of colorectal cancer with increasing intake was found for bread and cereal dishes (odds ratio for increase of one daily serving 1.11), cakes and desserts (odds ratio 1.02) and refined sugar (odds ratio 1.11). The intake of fish (odds ratio 0.53), raw and cooked vegetables (odds ratios 0.79 and 0.65, respectively) and fruit (odds ratio 0.93) showed an inverse association with risk. Wholemeal bread was consumed by only 12.5% of cases and 13.9% of controls and, at variance with refined bread, did not show a significant direct association with colorectal cancer risk (odds ratio 0.88). In view of these findings, current hypotheses on the carcinogenic effects of refined starchy foods and refined sugar should be revised to take into account the digestive physiology of carbohydrates and the possible relationship between insulin and colon cancer. The beneficial influence of most vegetables is confirmed, and a possible difference between refined and wholemeal bread is suggested.
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PMID:Italian study on colorectal cancer with emphasis on influence of cereals. 969 38

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.
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PMID:Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy. 977 41

In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.
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PMID:Dietary risk factors for colon cancer in a low-risk population. 978 31

Obesity is a known risk factor for a number of diseases with serious mortality and morbidity implications. Thus, obesity is an economic burden to communities, since it reduces quality of life and leads to premature mortality; in addition, healthcare resources are used to manage obesity-related disease. It was estimated that in 1989, management of disease due to obesity (defined as body mass index greater than 30) cost A$395 million. This estimate covers the healthcare costs for the management of obesity, non-insulin-dependent diabetes mellitus (NIDDM), gallstones, hypertension, coronary heart disease (CHD), breast cancer (among postmenopausal women), and colon cancer. As this estimate excludes the costs of some disease attributable to obesity, it is an underestimate of the true costs. Nonetheless, the estimated cost of the management of obesity-related conditions represents 86% of the healthcare costs used for the management of alcohol-related diseases in Australia. Healthcare costs attributable to obesity have not yet been estimated for countries elsewhere in Asia and the Pacific. However, it is acknowledged that obesity is a major problem in the Pacific, with exceptionally high prevalence rates and concomitant high rates of diseases for which obesity is a major risk factor, particularly NIDDM and CHD. It would, therefore, be useful to explore the cost of disease attributable to obesity in healthcare systems in these communities, and the potential for preventive programmes to reduce these costs.
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PMID:The cost of obesity: the Australian perspective. 1014 49

Energy balance results from the exact equilibrium between caloric intake and caloric expenditure. A caloric intake larger than caloric expenditure results in overweight, even obesity, but other determinants, like hormonal dysfunction and/or genetic traits may play a part in obesity syndrome. Obesity, and even overweight, have been recognized as risk factors for the development of cancers. Human epidemiological studies, which have tended to establish the nature of the relationship between energy balance and cancer, are summarized first, with the influence of the various factors which act both on obesity and on cancer risk. Among these factors are the macronutrients responsible for the caloric intake, and some lifestyle factors (physical activity, drinking habits and tobacco use). Second, the animal studies help to distinguish between different relevant factors, and to understand some of the underlying mechanisms. However, the insulin-resistance syndrome, which appears to underlie the relationship between obesity and hormone-dependent cancers, and possibly colon cancer, is only relevant to human physiology because hormonal alterations are part of it. Prevention of hyperinsulinemia, insulin resistance and the accompanying visceral obesity appears to be a major public health task for the prevention of cancers.
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PMID:Energy balance and cancers. 1033 54


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