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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colon cancer was rare or uncommon in the past, and still is in traditionally-living third world populations. It now affects 3-5% of western populations. Epidemiological, case control, experimental and other studies suggest that proneness to colon cancer can be lessened by major dietary changes, principally decreasing fat intake by a third, and doubling the intake of fiber-containing foods, especially vegetables and fruit--recommendations similarly advocated for the avoidance of coronary heart disease and other degenerative diseases. Among nondietary factors, evidence indicates familiality, obesity and atmospheric pollution to be contributory, while parity, physical activity, solar radiation, high social class, estrogen use, and aspirin use, appear protective. Despite insufficiencies of knowledge of prevention, avoiding action should certainly be taken by those familially prone. For the rest, conceivably a prudent life-style could benefit a proportion avoiding colon cancer.
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PMID:Can the risk of colon cancer be lessened? 830 89

An increase in the risk of cancer is one of the consequences of obesity. The predominant cancers associated with obesity have a hormonal base and include breast, prostate, endometrium, colon and gallbladder cancers. As the basis for understanding the problem of obesity has advanced, a number of new ideas have emerged about the relationship of obesity to cancer. The conversion of androstenedione secreted by the adrenal gland into estrone by aromatase in adipose tissue stroma provides an important source of estrogen for the postmenopausal woman. This estrogen may play an important role in the development of endometrial and breast cancer. Of interest is that experimental animals lacking aromatase or the estrogen receptor alpha are obese. Leptin is one of the many products produced by fat cells and has given rise to the ideas that the fat cell is an endocrine cell and that adipose tissue is an endocrine organ. The increased release of cytokines from this tissue may play a role in the inflammatory state that is associated with obesity. The gut also plays an important role in signaling satiety in response to food intake. Colon cancer is an important human disease, and experimental mice lacking gastrin are obese and have an increased risk of developing colon cancer in response to carcinogenic drugs. Efforts to control obesity through preventive strategies and treatment can be expected to have a benefit in reducing the risk of cancer.
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PMID:The underlying basis for obesity: relationship to cancer. 1242 69

We hypothesize that the peroxisome proliferator-activated receptor-gamma (PPARgamma) is associated with colorectal cancer given its association with insulin, diabetes, obesity, and inflammation. In this study, we evaluated the association between colorectal cancer and specific tumor mutations and the Pro12Ala (P12A) PPARgamma polymorphism. We also evaluated interactions between the PPARgamma gene and other insulin-related genes and use of aspirin and non-steroidal anti-inflammatory drug use. Data were available from 1,577 cases of colon cancer that were matched to 1,971 population-based controls and 794 cases of rectal cancer that were matched to 1,001 population-based controls. Colon tumors from the case subjects were evaluated for p53 and Ki-ras mutations and microsatellite instability (MSI). Insulin-related genes evaluated were the Bsm1, polyA, and Fok1 polymorphisms of the VDR gene; the G972R IRS1 polymorphism; the G1057D IRS2 polymorphism; the 19CA repeat polymorphism of the IGF1 gene; and the -200A>C IGFBP3 polymorphism. The odds ratio (OR) between the PA/AA genotypes and proximal tumors was 0.83 (95% CI: 0.69-1.01); for distal tumors was 1.00 (95% CI: 0.83-1.21); and for rectal tumors was 1.04 (95% CI: 0.86-1.25). Evaluation of specific types of tumor mutations showed that colon cancer cases with the PA or AA genotypes were less likely to have p53 tumor mutations (OR 0.78; 95% CI: 0.62-0.99), specifically transition mutations (OR 0.74; 95% CI: 0.56-0.97). Colon cancer cases also were less likely to have a tumor with MSI if they had the PA or AA PPARgamma genotype (OR 0.68; 95% CI: 0.47-0.98); differences in Ki-ras mutations were not seen in colon tumors by PPARgamma genotype. Those who did not take ibuprofen-type drugs and had the PA or AA genotypes were at a significantly greater risk of rectal cancer (OR 2.11; 95% CI: 1.52-2.92; p interaction 0.03) than people with the PP genotype regardless of ibuprofen-type drug use. There was a significant interaction between the -200A>C IGFBP3 polymorphism and the Pro12Ala PPARgamma polymorphism and risk of colon cancer (p for interaction = 0.02) with individuals being at significantly lower risk if they had both the CC IGFBP3 genotype and the PA/AA PPARgamma genotype. For rectal cancer there was a significant interaction between the Bsm1/polyA polymorphisms (p = 0.001) of the VDR gene and the PA/AA Pro12Ala PPARgamma polymorphism with the highest risk group being those with both the PA/AA Pro12Ala PPARgamma and the BB/SS VDR genotypes. These data suggest that PPARgamma may be associated with many aspects of colorectal cancer including insulin- and inflammation-related mechanisms.
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PMID:PPARgamma and colon and rectal cancer: associations with specific tumor mutations, aspirin, ibuprofen and insulin-related genes (United States). 1648 31

PTEN is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. Recent studies have also demonstrated that PTEN is a promising target in type II diabetes and obesity treatment. Using C-terminal PTEN sequence in pEG202-NLS as bait, yeast two-hybrid screening on Mouse Embryo, Colon Cancer, and HeLa cDNA libraries was carried out. Isolated positive clones were validated by mating assay and identified through automated DNA sequencing and BLAST database searches. Sequence analysis revealed a number of PTEN-binding proteins linking this phosphatase to a number of different signaling cascades, suggesting that PTEN may perform other functions besides tumor-suppressing activity in different cell types. In particular, the interplay between PTEN function and adipocyte-specific fatty-acid-binding protein FABP4 is of notable interest. The demonstrable tautology of PTEN to FABP4 suggested a role for this phosphatase in the regulation of lipid metabolism and adipocyte differentiation. This interaction was further studied using coimmunoprecipitation and gel-filtration assays. Finally, based on Biacore assay, we have calculated the K(D) of PTEN-FABP4 complex, which is around 2.8 microM.
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PMID:Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4. 1991 Dec 53

Colorectal cancer is the third most common malignancy in men and women and accounts for 10% of all cancer deaths. The primary risk factor for colorectal cancer is advancing age, but other factors also play a role in its development, including genetic predisposition, smoking, alcohol consumption, obesity, and high-fat, low-fiber diet. Colon cancer survival is primarily related to the stage of disease at diagnosis. The main screening tests for colon cancer are fecal occult blood testing, flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy. The pre-operative evaluation should include a complete blood count, carcinoembryonic antigen (CEA), colonoscopy, and chest radiograph. Other preoperative evaluations are patient specific or of unproven benefit. The operative procedure should include a bowel preparation, parenteral antibiotics, and deep venous thrombosis prophylaxis. The procedure performed must be tailored to the location of the colon cancer but should include complete, en bloc resection of the cancer and its lymphatic drainage, including locally invaded structures. The bowel margins of resection should be at least 5 cm from the tumor to minimize anastomotic recurrences. Laparoscopic colectomy has been shown to be as safe and effective as open colectomy for the treatment of colon cancer. The use of sentinel lymph node biopsy is feasible but has not yet been proved clinically useful. Surveillance after surgery for colon cancer is necessary to monitor for metastatic disease or local recurrence. Several groups have made surveillance recommendations including office visits, colonoscopy, and CEA monitoring.
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PMID:Preoperative evaluation and oncologic principles of colon cancer surgery. 2001 Dec 99

The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992-2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of > or = 3.0 mg/L versus <1.0 mg/L were 1.36 (95% confidence interval (CI): 1.00, 1.85; P-trend = 0.01) for colon cancer and 1.02 (95% CI: 0.67, 1.57; P-trend = 0.65) for rectal cancer. Colon cancer risk was significantly increased in men (relative risk = 1.74, 95% CI: 1.11, 2.73; P-trend = 0.01) but not in women (relative risk = 1.06, 95% CI: 0.67, 1.68; P-trend = 0.13). Additional adjustment for C-peptide, glycated hemoglobin, and high density lipoprotein cholesterol did not attenuate these results. These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia.
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PMID:Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. 2063 78

Colon cancer represents a highly prevalent disease in the Western world. While dietary and lifestyle recommendations remain important factors in disease prevention and treatment, epidemiological data have made it clear that obesity and excess body weight remain significant risk factors for the disease. A number of potential direct and indirect relationships exist between obesity and increased risk of colon cancer. Several mechanisms which appear promising and warrant further investigation are discussed here, specifically the modifying role of insulin and insulin-like growth factors, leptin, adipose-tissue induced changes in estrogens and androgens, and inflammatory molecules. A brief review of these hormones and signaling molecules and their action in colon cancer development is described. A thorough integration and understanding of the mechanisms of action these systems exert on colonic epithelia will be important in designing studies and experiments aimed at elucidating disease etiology for prevention and treatment.
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PMID:Roles of hormones and signaling molecules in describing the relationship between obesity and colon cancer. 2122 74

A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis.
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PMID:Diet induced obesity increases the risk of colonic tumorigenesis in mice. 2353 80

Colorectal cancer is one of the leading causes of cancer-related deaths in the United States, and generally, as countries climb the economic ladder, their rates of colon cancer increase. Colon cancer was an early disease where key genetic mutations were identified as important in disease progression, and there is considerable interest in determining whether specific mutations sensitize the colon to cancer prevention strategies. Epidemiological studies have revealed that fiber- and vegetable-rich diets and physical activity are associated with reduced rates of colon cancer, while consumption of red and processed meat, or alcoholic beverages, and overconsumption as reflected in obesity are associated with increased rates. Animal studies have probed these effects and suggested directions for further refinement of diet in colon cancer prevention. Recently a central role for the microorganisms in the gastrointestinal tract in colon cancer development is being probed, and it is hypothesized that the microbes may integrate diet and host genetics in the etiology of the disease. This review provides background on dietary, genetic, and microbial impacts on colon cancer and describes an ongoing project using rodent models to assess the ability of digestion-resistant starch in the integration of these factors with the goal of furthering colon cancer prevention.
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PMID:Diet, genes, and microbes: complexities of colon cancer prevention. 2412 59

Colon cancer is the cancer of the large intestine (colon), which is located in the lower part of digestive system. Colon cancer is the third most common cancer in men and the second in women worldwide.Genetic background is thought to play a role in modulating individual risks of this cancer.Many studies support an association between insulin pathway gene polymorphisms and regulation of tumor cell biology in colorectal cancer. This review examines the role of polymorphisms of insulin and obesity pathway genes (IGFs, INS, INSR, ADIPOQ, ADIPOQR, LEP and LEPR) in development of colorectal cancer.
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PMID:The Association between Polymorphismsin Insulin and Obesity Related Genesand Risk of Colorectal Cancer. 2525 Jan 32


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