Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modifiable risk factors in colorectal cancer etiology and their interactions with genetic susceptibility are of particular interest. Functional vitamin D receptor (VDR) gene polymorphisms may influence carcinogenesis through modification of cell growth, protection from oxidative stress, cell-cell matrix effects, or insulin and insulin-like growth factor pathways. We investigated interactions between foods (dairy products, red and processed meat, and whole and refined grains) and dietary patterns (sucrose-to-fiber ratio and glycemic index) associated with insulin resistance with the FokI polymorphism of the VDR gene and colon and rectal cancer risk. Data (diet, anthropometrics, and lifestyle) and DNA came from case-control studies of colon (1,698 cases and 1,861 controls) and rectal cancer (752 cases and 960 controls) in northern California, Utah, and the Twin Cities metropolitan area, Minnesota (colon cancer study only). Unconditional logistic regression models were adjusted for smoking, race, sex, age, body mass index, physical activity, energy intake, dietary fiber, and calcium. The lowest colon cancer risk was observed with the Ff/ff FokI genotypes and a low sucrose-to-fiber ratio. Rectal cancer risk decreased with greater consumption of dairy products and increased with red or processed meat consumption and the FF genotype. Modifiable dietary risk factors may be differentially important among individuals by VDR genotype and may act through the insulin pathway to affect colon cancer risk and through fat, calcium, or other means to influence rectal cancer risk.
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PMID:Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer. 1696 39

Initially, it was hoped that resistant starches (ie, starches that enter the colon) would have clear advantages in the reduction of colon cancer risk and possibly the treatment of ulcerative colitis. Recent studies have confirmed the ability of resistant starch to increase fecal bulk, to increase the molar ratio of butyrate in relation to other short-chain fatty acids, and to dilute fecal bile acids. However, reduction in fecal ammonia, phenols, and N-nitroso compounds have not been achieved. At this point the picture from the standpoint of colon cancer risk reduction is not clear. Nevertheless, there is a fraction of what has been termed resistant starch (RS1), which enters the colon and acts as slowly digested, or lente, carbohydrate. Foods in this class are low glycemic index and have been shown to reduce the risk of chronic disease. They have been associated with systemic physiologic effects such as reduced postprandial insulin levels and higher high-density lipoprotein cholesterol levels. Consumption of low glycemic index foods has been shown to be related to a reduced risk of type 2 diabetes. Type 2 diabetes has in turn been related to a higher risk of colon cancer, especially colon cancer deaths. If carbohydrate has a protective role in colon cancer prevention, it may lie in the systemic effects of low glycemic index foods. The colonic advantages of different carbohydrates, therefore, remain to be documented. However, there is reason for optimism about the possible health advantages of so-called resistant starches that are slowly digested in the small intestine.
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PMID:Resistant starches. 1702 38

The metabolic syndrome is composed of cardiovascular risk factors including increased body mass index/waist circumference, blood pressure, plasma glucose, and triglycerides, as well as decreased high-density lipoprotein cholesterol. The essence of the metabolic syndrome lies in the clustering of these risk factors, which are associated with cardiovascular disease. Interestingly, most of the components of the metabolic syndrome have individually been linked in some way to the development of cancer. However, epidemiological studies linking the metabolic syndrome to cancer are scarce. Nevertheless, two such studies indicate that the clustering of metabolic syndrome components significantly increases the risk of colon cancer mortality compared with the individual components. The purpose of this review is to further explore the potential relationship between the metabolic syndrome and cancer risk. Specifically, we examine the hypothesis that individual components of the metabolic syndrome contribute to the development of several processes, including insulin resistance, aromatase activity, adipokine production, angiogenesis, glucose utilization, and oxidative stress/DNA damage, which can work together to increase cancer risk beyond that of the individual components alone. We propose that the metabolic syndrome be considered as a high-risk state for certain types of cancer and that this relationship should be systematically explored across cancer types.
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PMID:The metabolic syndrome: A high-risk state for cancer? 1707 76

Adjuvants are essential components of vaccines that augment an immunological reaction of organism. New vaccines based on recombinant proteins and DNA, are more save than traditional vaccines but they are less immunogenic. Therefore, there is an urgent need for the development of new, improved vaccine adjuvants. There are two classes of adjuvants: vaccine delivery systems (e.g. emulsions, microparticles, immune-stimulating complexes ISCOMs, liposomes) and immunostimulatory adjuvants (e.g. lipopolysaccharide, monophosphoryl lipid A, CpG DNA, or muramylpeptides). The discovery of more potent and safer adjuvants may allow to development better prophylactic and therapeutic vaccines against chronic infectious (e.g., HSV, HIV, HCV, HBV, HPV, or Helicobacter pylori) and noninfectious diseases as multiple sclerosis, insulin-dependent diabetes, rheumatoid arthritis, allergy and tumors (e.g., melanoma, breast, or colon cancer).
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PMID:[Adjuvants--essential components of new generation vaccines]. 1707 10

While the fundamental metabolic function of calcium is to serve as a second messenger, coupling intracellular responses to extracellular signals, nutritional deficiency of calcium is manifested at a higher level of organization: 1) depletion of the calcium nutrient reserve; 2) inadequate complexation of digestive byproducts; and 3) collateral effects of hormones produced primarily to compensate for low calcium intake. The first mechanism contributes to the osteoporosis problem, the second to kidney stones and colon cancer, and the third to hypertension, preeclampsia, obesity, and insulin resistance, among others. Adequate calcium intakes (1000-1500 mg/d) in adults have been shown in controlled trials to lower the risk of osteoporotic fractures, kidney stones, obesity, and hypertension. The best source of calcium is dairy foods, largely because the disorders concerned depend upon multiple nutrients, not just calcium, and dairy provides a broad array of essential nutrients in addition to calcium, and at low cost.
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PMID:Calcium intake and disease prevention. 1711 94

Diets with a high glycemic index and glycemic load have been hypothesized to be implicated in the etiology of colorectal cancer owing to their potential to increase postprandial glucose and insulin levels. Prospective data on glycemic index and glycemic load in relation to colorectal cancer risk are limited and inconsistent. Therefore, the authors prospectively investigated the associations of dietary carbohydrate, glycemic index, and glycemic load with the incidence of colorectal cancer among 61,433 Swedish women who were free of cancer in 1987-1990 and completed a 67-item food frequency questionnaire. During follow-up through June 2005, 870 incident cases of colorectal adenocarcinoma were diagnosed. Carbohydrate intake, glycemic index, and glycemic load were not associated with risk of colorectal cancer, colon cancer, or rectal cancer. The multivariate hazard ratios for colorectal cancer comparing the highest with the lowest quintile were 1.10 (95% confidence interval: 0.85, 1.44) for carbohydrate intake, 1.00 (95% confidence interval: 0.75, 1.33) for glycemic index, and 1.06 (95% confidence interval: 0.81, 1.39) for glycemic load. Results did not vary by body mass index. The findings from this prospective study do not support the hypothesis that a high carbohydrate intake, a high glycemic index, and a high glycemic load increase the risk of colorectal cancer.
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PMID:Dietary carbohydrate, glycemic index, and glycemic load in relation to risk of colorectal cancer in women. 1711 65

The physical inactivity and obesity involved in hyperglycemia and hyperinsulinemia is supposed to lead to an increased bioavailability of insulin-like growth factor-I (IGF-I). The carcinogenic effect of IGF-I may be influenced by IGF binding proteins. We investigated the association between plasma levels of C-peptide, a surrogate biomarker of insulin, IGFBP-1, IGF-I or IGFBP-3, and the risk of colorectal cancer in a nested case-control study. During an 11.5-year follow-up, 375 newly diagnosed colorectal cancers were identified in a cohort of 38,373 adults who had returned the baseline questionnaire and provided blood samples. Two matched-controls for each case were selected from the cohort. The odds ratio (OR) of colorectal cancer for plasma levels of each protein was estimated using the conditional logistic regression model adjusted for potential confounding factors. We observed a statistically significant association of plasma C-peptide with colorectal cancer only in men. The ORs were 1.0, 2.3, 2.8 and 3.2 along with quartiles (p trend, 0.0072). The association was stronger in colon cancer (p trend, 0.025) than in rectal cancer (p trend, 0.24). Other peptides were not associated with the risk in either men or women. The results did not change when repeatedly analyzed by tumor invasion levels, tumor sites or follow-up periods. In conclusion, a higher plasma C-peptide may indicate a subsequent risk of colorectal cancer in Japanese men.
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PMID:Plasma C-peptide, insulin-like growth factor-I, insulin-like growth factor binding proteins and risk of colorectal cancer in a nested case-control study: the Japan public health center-based prospective study. 1726 31

Energy-adjusted magnesium intake was nonsignificantly inversely related to risk of colorectal cancer (n=2328) in the Netherlands Cohort Study on Diet and Cancer that started in 1986 (n=58 279 men and 62 573 women). Statistically significant inverse trends in risk were observed in overweight subjects for colon and proximal colon cancer across increasing quintiles of magnesium uptake (P-trend, 0.05 and 0.02, respectively). Although an overall protective effect was not afforded, our results suggest an effect of magnesium in overweight subjects, possibly through decreasing insulin resistance.
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PMID:Magnesium intake and colorectal cancer risk in the Netherlands Cohort Study. 1728 23

Insulin-like growth factors are known to inhibit apoptosis and promote tumour angiogenesis. Previously we have shown that insulin-like growth factor binding protein-4 (IGFBP-4) gene therapy increased apoptosis and decreased mitosis in colon cancer. In this experiment we used HT-29 colon cancer cells to induce subcutaneous cancers in nude mice and administered either the mammalian expression vector with IGFBP-4 insert or vector only around the tumour site. Three weeks after gene transfer, tumours were harvested and expressions of Bax, Bcl-2 and IGF-I receptor in tumours were determined by Western blotting and immunofluorescence. Micro-vessel counting was performed by immunostaining with CD34 and von Willebrand antibodies. Results showed that tumours treated with IGFBP-4 gene had higher expression of Bax, lower expression of Bcl-2 and IGF-I receptor. Bcl-2 was localised to tumour cell cytoplasm while Bax was expressed both in the interstitial area and cytoplasm. IGFBP-4 treatment also decreased micro-vessel count in tumour tissues. Micro-vessels were mainly located in the periphery and interstitial area. This experiment shows that IGFBP-4 gene therapy increases tumour apoptosis via altering the expressions of Bcl-2 and Bax and decreasing the angiogenesis in colorectal cancer.
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PMID:Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer. 1733 27

Glycogen synthase kinase 3beta (GSK 3beta) is a key component of several cellular processes including Wnt and insulin signalling pathways. The interaction of GSK3beta with scaffolding peptide axin is thought to be responsible for the effective phosphorylation of beta-catenin, the core effector of Wnt signaling, which has been linked with the occurrence of colon cancer and melanoma. It has been demonstrated that the binding of axin to GSK3beta is abolished by the single-point mutation of Val267 to Gly (V267G) in GSK3beta or Leu392 to Pro (L392P) in axin. Molecular dynamics (MD) simulations were performed on wild type (WT), V267G mutant and L392P one to elucidate the two unbinding mechanisms that occur through different pathways. Besides, rough energy and residue-based energy decomposition were calculated by MM_GBSA (molecular mechanical Generalized_Born surface area) approach to illuminate the instability of the two mutants. The MD simulations of the two mutants and WT reveal that the structure of GSK3beta remains unchanged, while axin moves away from the interfacial hydrophobic pockets in both two mutants. Axin exhibits positional shift in V267G mutant, whereas, losing the hydrogen bonds that are indispensable for stabilizing the helix structure of wild type axin, the helix of axin is distorted in L392P mutant. To conclude, both two mutants destroy the hydrophobic interaction that is essential to the stability of GSK3beta-axin complex.
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PMID:Insights into unbinding mechanisms upon two mutations investigated by molecular dynamics study of GSK3beta-axin complex: role of packing hydrophobic residues. 1738 Apr 82


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