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)

The UDP-glucuronosyltransferase 1A1 (UGT1A1) gene product catalyzes the glucuronidation of serum bilirubin as part of normal heme catabolism. Recently, TA repeat polymorphisms containing five, six, seven, and eight TA dinucleotides in a putative TATA box in the promoter region of the UGT1A1 gene have been described. TA repeat number modulates UGT1A1 transcriptional activity and the quantity of enzyme available to conjugate serum bilirubin. Serum bilirubin is a known antioxidant, and low serum bilirubin has been associated with increased risk for coronary artery disease and inhibition of reactive oxygen species (ROS)-induced damage to erythrocytes in vitro. We hypothesize that the UGT1A1 TA repeats or other functional polymorphisms resulting in lower serum bilirubin levels may be predictive of genetic susceptibility to oxidative damage and cancer. Exposure-related or endogenous production of ROS may impact the integrity of cellular macromolecules and infrastructure, lead to DNA base changes or chromosomal aberrations, and induce toxicity or apoptosis. ROS damage to lipoproteins may be a factor in formation of atherogenic plaques in coronary heart disease. Thus, cellular oxidative stress could contribute to tumorigenesis through mutagenic or epigenetic pathways, and higher serum bilirubin levels should inhibit this process. No definitive studies have been performed, but in a small prospective study of colon cancer, serum bilirubin levels were observed to be lower in these cases. Another study has suggested a link between UGT1A1 alleles, estrogen metabolism, and risk in breast cancer. Epidemiologic studies examining variation in ROS metabolism, ROS damage, bilirubin, and cancer risk will demonstrate the value of this hypothesis.
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PMID:Bilirubin UDP-glucuronosyltransferase 1A1 gene polymorphisms: susceptibility to oxidative damage and cancer? 1117 Feb 57

Many genetic, environmental, behavioral, and cultural factors affect health. Diet is as vital as any of them for preventing disease and promoting well-being. We know that what we eat can lead to premature disability and mortality: to obesity, coronary heart disease, type 2 diabetes, degenerative arthritis, sleep apnea, and other illnesses. Now scientific evidence points to links between dietary patterns and illness. The study of these links is a new approach to understanding the role that diet plays in chronic disease. Initial studies include those on eating patterns and risk of colon cancer. More recently, researchers have investigated all-cause mortality and leading causes of chronic disease. Novel epidemiological approaches include factorial analysis to evaluate dietary patterns and cluster analysis to examine nutrient intake, gender, and weight status across food-pattern clusters. These methods work best within groups to identify major dietary patterns, but not necessarily ideal diets. They may also differ across population groups. The success of the Dietary Approaches to Stop Hypertension and Lyon Diet Heart studies supports the value of dietary pattern analysis. At the same time, the relative failure of single-nutrient studies underscores the need for new methodologies and directions in research.
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PMID:Treatment approaches: food first for weight management and health. 1170 45

The results of the Women's Health Initiative's (WHI) large prospective randomized controlled study on the benefits and risks of combined hormone replacement therapy (HRT) have been reported earlier than expected, due to the findings of a small excess in cases of breast cancer, myocardial infarction, cerebrovascular accident, and venous thrombosis, in conjunction with a slight diminution of the number of cases of bone fracture and colon cancer. These results were obtained in a population of women with a mean age of 63 +/- 7 years, many of whom were already presenting relative risks of diseases at randomization. The results provide the best evidence available at present on HRT for prevention of heart disease, and indicate that combined HRT is not indicated for this purpose in the studied population, thus contradicting the reported beneficial effects of HRT on coronary heart disease (CHD) in previous observational studies. Some comments need to be made, particularly with regard to the relevance of the WHI study results to the traditional use of HRT at the beginning of menopause. The results, obtained from a population having a wide age range (50 to 79 years), with only 33% being between the ages of 50 and 59, taking 0.625 mg/day conjugated equine estrogens combined with 2.5 mg/day medroxyprogesterone acetate or placebo, are presented without stratification according to the various decades. Further, 73.9% of the women never took HRT before entering the study; rather, they began HRT several years after menopause. Thus, the age distribution and late start of HRT in the women in the WHI study do not correspond to the traditional use of HRT. The studied population presented numerous risks of diseases related to aging, in particular cardiovascular disease. Except for venous thrombosis, the confidence intervals for outcomes are near the limit of statistical significance, which disappears after adjustment. The accrual of breast cancer cases appearing during the fourth year of observation is similar to that found in previous studies, and remains inferior to the increases related to lifestyle factors reported in other studies. The overall results are being applied to women aged 50 to 60 without specific data for this age group, who are usually considered to be at no or low risk for the traditional use of HRT. There are no data to compare the various formulations actually approved as class labelling (estrogens or estradiol associated or not with a progestin or natural progesterone by the oral or transdermal route) in the various outcomes of the WHI study. Results of the ongoing WHI study on estrogen alone will have to be considered when they become available. The results of the WHI study do not put into question the validity of prescribing combined HRT in early menopause. They are likely to modify somewhat the recommendations of published consensus cautioning the use of HRT. HRT remains an effective and safe intervention when it is prescribed to palliate the signs and symptoms related to estrogen deficiency, mainly in women soon after menopause, but also in women presenting risk factors for osteoporosis but without actual risk factors of cardiovascular disease and without a family history of breast cancer. New mid-term and long-term randomized studies need to be conducted on women starting various formulations of HRT before the age of 60, to evaluate their impact on risk factors and events of cardiovascular disease.
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PMID:The relevance of the Women's Health Initiative results on combined hormone replacement therapy in clinical practice. 1236 Mar 60

Soybeans are a natural dietary source of isoflavones, which have estrogen-like properties. Therefore, it is worthwhile to consider the implications for soy of the recently published findings of the Heart and Estrogen/Progestin Replacement Study (HERS) I/II and the Women's Health Initiative (WHI). The WHI found coronary heart disease (CHD) risk to be increased in women receiving hormone replacement therapy, and both studies found increases in venous thromboembolic disease in such women. Additionally, stroke and breast cancer risk were increased in the WHI, although risk of colorectal cancer and fracture was decreased. Because research suggests that it is the combination of estrogen plus progestin, and not estrogen alone, that increases breast cancer risk, soy seems unlikely to increase risk because it has no progestin activity. Similarly, there is no evidence to suggest that soy will increase venous thromboembolic disease or stroke; however, only limited data are available in this area. There are promising data suggesting that soy may decrease CHD risk, although studies conducted thus far have examined only markers of risk and not actual CHD events. Similarly, short-term studies generally suggest that soy reduces bone loss in postmenopausal women; however, such effects have been noted primarily only at the spine, and longer-term studies are needed. Finally, very limited human research suggests that soy may decrease colon cancer risk, but this is highly speculative. The results of HERS I/II and WHI suggest that soy may have some of the advantages, but not the disadvantages, of combined hormone replacement therapy (at least with respect to the specific hormones and doses used in the HERS I/II and WHI), but that large, long-term intervention studies examining disease outcome are needed before definitive conclusions can be drawn. Nevertheless, the evidence warrants recommendations that menopausal women include soy in their diets.
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PMID:Soy foods and soybean isoflavones and menopausal health. 1255 10

Regular physical activity provides health benefits, including the reduction in risks of coronary heart disease, hypertension, type 2 diabetes mellitus, obesity, colon cancer, and premature mortality. Despite this information, most women are physically inactive. Research findings shed light on the gender differences in physiological responses to physical activity. Patterns and predictors of physical activity vary significantly by gender. Further study is needed of the benefits, barriers, and personally meaningful outcomes of physical activity for women, specifically including the frequently unspoken correlates of urinary incontinence, depression and mood disorders, and obesity.
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PMID:Physical activity and exercise in women's health. 1506 35

It was initially hypothesized that resistant starches, i.e., starch that enters the colon, would have protective effects on chronic colonic diseases, including reduction of colon cancer risk and in the treatment of ulcerative colitis. Recent studies have confirmed the ability of resistant starch to increase fecal bulk, increase the molar ratio of butyrate in relation to other short-chain fatty acids, and dilute fecal bile acids. However the ability of resistant starch to reduce luminal concentrations of compounds that are damaging to the colonic mucosa, including fecal ammonia, phenols, and N-nitroso compounds, still requires clear demonstration. As such, the effectiveness of resistant starch in preventing or treating colonic diseases remains to be assessed. Nevertheless, there is a fraction of what has been termed resistant (RS1) starch, which enters the colon and acts as slowly digested or lente carbohydrate in the small intestine. 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 physiological effects such as reduced postprandial insulin levels and higher HDL cholesterol levels. Consumption of low glycemic index foods has been shown to be related to reductions in risk of coronary heart disease and Type 2 diabetes. Type 2 diabetes has in turn been related to a higher risk of colon cancer. If carbohydrates have a protective role in colon cancer prevention this may lie partly in the systemic effects of low glycemic index foods. The colonic advantages of different carbohydrates, varying in their glycemic index and resistant starch content, therefore, remain to be determined. However, as recent positive research findings continue to mount, there is reason for optimism over the possible health advantages of those resistant starches, which are slowly digested in the small intestine.
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PMID:Resistant starches and health. 1528 78

Apolipoprotein E (apoE) plays a major role in the metabolism of bile acids, cholesterol and triglycerides, and has recently been proposed as being involved in the carcinogenic process. Given the potential role of bile acids in colorectal cancer etiology, it is reasonable that colorectal cancer risk might be modified by apoE genotype. We used data collected from a case-control study of colon cancer (n=1556 cases and 1948 controls) and rectal cancer (n=777 cases and 988 controls). The absence of an e3 apoE allele significantly increased the risk of colon cancer (OR=1.37 95% CI 1.00-1.87), particularly among those diagnosed when older than 64 years (OR=1.88 95% CI 1.17-3.04; P interaction between age and apoE genotype equal to 0.05). A significant three-way interaction was detected for family history of colorectal cancer, age at diagnosis and apoE genotype (P = 0.05), in those diagnosed when older, not having an e3 allele and having a significantly increased risk of colon cancer with family history of colorectal cancer (OR=3.93 95% CI 1.23-12.6). This was compared with the risk associated with family history of colorectal cancer among those diagnosed when older, with an e3 allele of 1.61 (95% CI 1.17-2.23) or those diagnosed when younger without an e3 allele (OR=2.40 95% CI 0.56-10.3). Among those diagnosed when older than 64 years, associations of BMI and prudent diet with colon cancer were stronger among individuals without an e3 allele, although the P for interaction was not significant. We did not detect any significant associations between apoE genotype and rectal cancer, survival after diagnosis with colorectal cancer, stage of disease at diagnosis or type of tumor mutation. These findings suggest those apoE genotypes that do not include the e3 allele, the same genotypes that are associated with increased risk of coronary heart disease, may influence development of colon cancer among those who are older at diagnosis.
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PMID:Associations between apoE genotype and colon and rectal cancer. 1581 10

There is increasing evidence that mild dehydration plays a role in the development of various morbidities. In this review, the effects of hydration status on chronic diseases are categorized according to the strength of the evidence. Positive effects of maintenance of good hydration are shown for urolithiasis (category lb evidence); constipation, exercise asthma, hypertonic dehydration in the infant, and hyperglycemia in diabetic ketoacidosis (all category IIb evidence); urinary tract infections, hypertension, fatal coronary heart disease, venous thromboembolism, and cerebral infarct (all category III evidence); and bronchopulmonary disorders (category IV evidence). For bladder and colon cancer, the evidence is inconsistent.
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PMID:The importance of good hydration for the prevention of chronic diseases. 1602 66

Regular physical activity improves quality of life and reduces risk for coronary heart disease, colon cancer, hypertension, diabetes, and overall mortality. Physical activity also has been associated with reduced symptoms of depression and greater independence. A sedentary lifestyle is associated with obesity. However, despite the health benefits of physical activity, 23.1% of adults in the United States report they do not engage in any leisure-time physical activity. Neighborhood environment (e.g., sidewalks and street lighting), perceived trustworthiness of neighbors, and perceptions of neighborhood safety all have been associated with levels of physical activity. During 2004, to assess the association between these factors and leisure-time physical inactivity in eastern Travis County, Texas, the local health department collected and analyzed data by using the methodology of the Behavioral Risk Factor Surveillance System (BRFSS). This report describes the results of that analysis, which indicated that persons who perceived their neighborhoods as less than extremely safe were more than twice as likely to have no leisure-time physical activity, and those who perceived their neighborhoods as not at all safe were nearly three times as likely to have no leisure-time physical activity. Public health agencies promoting physical activity in neighborhoods should consider how residents perceive their safety and design programs that specifically address those safety concerns.
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PMID:Perceptions of neighborhood characteristics and leisure-time physical inactivity--Austin/Travis County, Texas, 2004. 1617 84

Obesity and its related diseases are the leading cause of death in western society, with associated risks of hypertension, coronary heart disease, stroke, diabetes, and breast, prostate and colon cancer. Recent epidemiologic data indicate an increased risk of Alzheimer's disease in association with adult obesity. There is now convincing evidence that, in both human and animal models, the in utero environment may impact on fetal developmental processes, altering offspring homeostatic regulatory mechanisms. "Gestational programming" may result in altered cell number, organ structure, hormonal set points or gene expression, with effects being permanent or expressed only at select offspring ages (e.g., newborn, adult). Our laboratory and others have demonstrated that low birth weight rats, induced by maternal food restriction or uterine artery ligation, paradoxically develop adult obesity with glucose intolerance and hypertension. Recent studies indicate alterations in peripheral (hepatic) and central (hippocampus) IGF-1 gene expression and epigenetic regulation among these offspring. These findings suggest that potential risk factors for the development of Alzheimer's disease may be present as early as newborn life.
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PMID:Gestational programming of offspring obesity: a potential contributor to Alzheimer's disease. 1743 Feb 49


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