Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes, obesity, and cigarette smoke, consistent risk factors for pancreatic cancer, are sources of oxidative stress in humans that could cause mitochondrial DNA (mtDNA) damage and increase mtDNA copy number. To test whether higher mtDNA copy number is associated with increased incident pancreatic cancer, we conducted a nested case-control study in the Alpha-Tocopherol Beta Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50 to 69 years at baseline. Between 1992 and 2004, 203 incident cases of pancreatic adenocarcinoma occurred (follow-up: 12 years) among participants, with whole blood samples used for mtDNA extraction. For these cases and 656 controls, we calculated ORs and 95% CIs using unconditional logistic regression, adjusting for age, smoking, and diabetes history. All statistical tests were two sided. Higher mtDNA copy number was significantly associated with increased pancreatic cancer risk (highest vs. lowest mtDNA copy number quintile, OR = 1.64, 95% CI = 1.01-2.67, continuous OR = 1.14, 95% CI 1.06-1.23), particularly for cases diagnosed during the first 7 years of follow-up (OR = 2.14, 95% CI = 1.16-3.96, P(trend) = 0.01, continuous OR = 1.21, 95% CI = 1.10-1.33), but not for cases occurring during follow-up of 7 years or greater (OR = 1.14, 95% CI = 0.53-2.45, continuous OR = 1.05, 95% CI = 0.93-1.18). Our results support the hypothesis that mtDNA copy number is associated with pancreatic cancer and could possibly serve as a biomarker for pancreatic cancer development.
 ...
PMID:Mitochondrial DNA copy number and pancreatic cancer in the alpha-tocopherol beta-carotene cancer prevention study. 2185 25

Adenocarcinoma of the pancreas is one of the top ten leading causes of cancer deaths and in the UK around 8,000 people are diagnosed with the disease each year. The incidence is similar in men and women and rises with age. Rates increase significantly in people aged 45 years and over and around three-quarters of patients diagnosed with pancreatic cancer are over the age of 65. Overall, the long-term prognosis of the disease is poor with a one-year survival rate of approximately 10-20%. The presenting symptoms are largely dependent on tumour location. Approximately half of patients are diagnosed with a tumour within the head of the pancreas and many of these will present with jaundice. Around half of patients with carcinoma of the head of pancreas will present with abdominal or back pain, which itself is an independent predictor of poor outcome. Rapid unintentional weight loss should raise clinical suspicion and is associated with shorter survival; and recent onset diabetes may serve as a warning sign. Individuals with two or more first-degree relatives with pancreatic cancer are at increased risk, even if no gene defect is identified. There are also a number of familial cancer syndromes which, although rare, carry a significantly higher risk. Patients with chronic pancreatitis from any aetiology have an approximately 15-fold higher risk than the general population, while diabetes mellitus, smoking and obesity have relative risks of around 2. In the UK, patients over the age of 40 with presenting symptoms of unexplained weight loss in combination with upper abdominal or back pain or late onset diabetes, in whom pancreatic cancer is suspected, should be referred for an urgent pancreatic protocol contrast-enhanced CT scan as a first-line investigation. GPs without direct access to CT should refer to a gastroenterologist or surgeon, in line with the two-week cancer target wait.
 ...
PMID:Diagnosing and managing pancreatic cancer. 2193 2

Cancer is associated with a fourfold increased risk of venous thromboembolism (VTE). The risk of VTE varies according to the type of malignancy (i. e. pancreatic cancer, brain cancer, lymphoma) and its disease stage and individual factors (i. e. sex, race, age, previous VTE history, immobilization, obesity). Preventing cancer-associated VTE is important because it represents a significant cause of morbidity and mortality. In order to identify cancer patient at particularly high risk, who need thromboprophylaxis, risk prediction models have become available and are under validation. These models include clinical risk factors, but also begin to incorporate biological markers. The major American and European scientific societies have issued their recommendations to guide the management of VTE in patients with cancer. In this review the principal aspects of epidemiology, risk factors and outcome of cancer-associated VTE are summarized.
 ...
PMID:Epidemiology, risk and outcomes of venous thromboembolism in cancer. 2197 78

The extremely poor outcome from pancreas cancer is well known. However, its aetiology less well appreciated, and the molecular mechanisms underlying this are poorly understood. Tobacco usage is one of the strongest risk factors for this disease, and this is a completely avoidable hazard. In addition, there are well described hereditary diseases which predispose, and familial pancreas cancer. We have sought here to summarise the role of tobacco-derived carcinogens and the mode of their tumorigenic action on the pancreas. There is compelling evidence from animal and human studies (laboratory including cell line studies and epidemiologic) that tobacco derived carcinogens cause pancreas cancer. However, the manner in which they do so is not entirely apparent. There is also compelling evidence that synergism with genetic and other life-style factors-like diet obesity-results in a multifactorial causation of the disease. Ascertaining the role of tobacco carcinogens in the development of this cancer and their interaction with other risk factors will enable novel therapeutic and preventative strategies to improve outcome from this appalling malignancy.
 ...
PMID:The role of tobacco-derived carcinogens in pancreas cancer. 2208 27

In the United States, pancreatic cancer is characterized by a low 5-yr survival rate of approximately 6%, fewer than 10% of patients diagnosed with localized disease and thus candidates for "curative" surgical resection, increasing incidence and few established risk factors. Similar statistics are observed for other industrialized nations. With new evidence to suggest that pancreatic cancer develops over a number of years, markers that can better identify high risk patients and are applicable to earlier diagnosis hold promise for improving these dire statistics. Obesity is one of the few modifiable risk factors that has been associated with increased risk of pancreatic cancer and also is related to increased risk of diabetes, a condition that in turn has been associated with pancreatic cancer development. Given recent data that nearly 70% of United States adults are overweight or obese, a clarification of the complex association between obesity and pancreatic cancer may disclose targets for prevention and intervention to decrease incidence and improve prognosis of this highly fatal disease. An overview of the current epidemiology and hypothesized biological mechanisms involved in the obesity-pancreatic cancer association are presented.
 ...
PMID:Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms. 2216 31

Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5-fold to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes-associated pancreatic cancer. Signaling pathways that regulate the metabolic process also play important roles in cell proliferation and tumor growth. Use of the antidiabetic drug metformin has been associated with reduced risk of pancreatic cancer in diabetics and recognized as an antitumor agent with the potential to prevent and treat this cancer. On the other hand, new-onset diabetes may indicate subclinical pancreatic cancer, and patients with new-onset diabetes may constitute a population in whom pancreatic cancer can be detected early. Biomarkers that help define high-risk individuals for clinical screening for pancreatic cancer are urgently needed. Why pancreatic cancer causes diabetes and how diabetes affects the clinical outcome of pancreatic cancer have yet to be fully determined. Improved understanding of the pathological mechanisms shared by diabetes and pancreatic cancer would be the key to the development of novel preventive and therapeutic strategies for this cancer.
 ...
PMID:Diabetes and pancreatic cancer. 2216 32

Although potentially modifiable risk factors for pancreatic cancer include smoking, obesity, and diabetes, less is known about the extent to which diet affects cancer risk. Recent studies have demonstrated some consistency for dietary fat being associated with elevated pancreatic cancer risk, particularly from animal sources. However, less is known about which fatty acids pose the greatest risk. Vitamin D, due to its endogenous production following UV-B exposure, is a unique risk factor in that researchers have created several methods to assess its exposure in humans. Studies that measured vitamin D exposure differently have shown inconsistent results. Dietary studies suggest protective associations, whereas studies of circulating 25-hydroxyvitamin D status show null or positive associations with low or very high concentrations, respectively. Several, but not all epidemiologic studies provide evidence of an inverse relationship between total and/or dietary folate and risk of pancreatic cancer. Protective associations for circulating folate are more often observed among populations with inadequate status. This article reviews the current epidemiological and experimental evidence investigating the relationship of dietary fat, vitamin D, and folate with pancreatic cancer. Additionally the mechanisms by which these risk factors may contribute to cancer, the methodological challenges involved with assessing risk, and other obstacles encountered when ascertaining the magnitude and direction of these three exposures are discussed.
 ...
PMID:Is dietary fat, vitamin D, or folate associated with pancreatic cancer? 2216 36

Although several reports have described a possible association between insulin-like growth factors-1 (IGF-1) and pancreatic cancer (PC) risk, this association has not been evaluated in the non-Caucasian population. To assess the impact of IGF-1 polymorphisms on PC risk in Japanese, we conducted a case-control study which compared the frequency of ten single nucleotide polymorphisms (SNPs) and haplotypes of IGF-1. SNPs were investigated using the TaqMan method in 176 patients with PC and 1402 control subjects. Exposure to risk factors was assessed from the results of a self-administered questionnaire. Associations and gene-environment interactions were examined using an unconditional logistic regression model. We did not observe any significant main effect of IGF-1 loci, but did find interactions between rs5742714 and past and/or current body-mass index (BMI) status. Among patients with BMI > 25 at age 20, an increased PC risk was observed with the addition of the minor allele for rs5742714 (trend P = 0.048) and rs6214 (P = 0.043). Among patients with current BMI > 25, an increased or decreased PC risk was observed with the addition of the minor allele for rs5742714 (trend P = 0.046), rs4764887 (P = 0.031) and rs5742612 (P = 0.038). Haplotype analysis of IGF-1 showed a significant association among patients who were either or both previously or currently overweight. These findings suggest that IGF-1 polymorphisms may affect the development of PC in the Japanese population in combination with obesity. Further studies to confirm these findings are warranted.
 ...
PMID:Interaction between IGF-1 polymorphisms and overweight for the risk of pancreatic cancer in Japanese. 2219 98

It has been reported that there is an association between pancreatic cancer and obesity, impaired glucose metabolism and diabetes based on excess dietary fat and sugar intakes. A number of studies have suggested that a high-fat diet increases development of carcinomas in various organs and possible risk factors for pancreatic cancer. However, how an excess sugar intake promotes pancreatic carcinogenesis is still unknown. In the present study, we investigated the influence of an excess sugar intake on pancreatic carcinogenesis by administration of a sucrose-rich diet in which starch was replaced by sucrose in order to contain the same calories and other nutrients. Two similar experiments were performed. Six-week-old male Syrian golden hamsters were given N-nitrosobis (2-oxopropyl) amine (BOP) at a dose of 50 and 20 mg/kg body weight as a carcinogen in Week 0 and 1, respectively. In Week 2, the animals were divided into control and experimental groups. In experiment 1, 15 animals received a control diet or sucrose-rich diet in which 100% of the starch was replaced by sucrose, respectively. Since five animals fed on the sucrose-rich diet died by Week 12, the diet was changed to a sucrose-rich diet in which 50% of the starch was replaced by sucrose. In experiment 2, 15 animals received a control diet or sucrose-rich diet in which 50 or 20% of the starch was replaced by sucrose, respectively. All animals were sacrificed 25 weeks after the start of the experiment, and histological examination of the pancreas was performed. No significant difference was seen in the body weight at the end of the experiment. There were no significant differences in the glycosylated hemoglobin (HbA1c) and serum triglyceride, total cholesterol and HDL-cholesterol levels between the control and sucrose-rich diet groups in experiments 1 and 2. The incidence and number of carcinomas increased in hamsters fed the sucrose-rich diet compared with the control diet in experiments 1 and 2. These results suggest that an excess sucrose intake may promote the development of pancreatic cancer in hamsters.
 ...
PMID:Promoting Effects of Sucrose-rich Diet on N-Nitrosobis (2-oxopropyl) amine-induced Pancreatic Carcinogenesis in Hamsters. 2227 7

Obesity is defined as BMI (calculated as weight in kg divided by height in m2) more than 30, and overweight is defined as BMI of 25-29.9. Obesity has been considered as a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. Severe acute pancreatitis is significantly more frequent in obese patients. Furthermore, obese patients develop systemic and local complications of acute pancreatitis more frequently. The underlying mechanisms are increased inflammation and necrosis from increased amount of intra- and peri-pancreatic fat. In addition, obesity is a poor prognostic factor in acute pancreatitis, and overweight before disease onset appears to be a risk factor for chronic pancreatitis. Overweight and/or obesity are associated with greater risk of pancreatic cancer and younger age of onset. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight. Long-standing diabetes increases the risk of pancreatic cancer. The pathogenic mechanism is that obesity and physical inactivity increase insulin resistance. In a state of hypersinulinemia, increased circulating level of insulin-like growth factor-1 induces cellular proliferation of pancreatic cancer. Obesity is associated with negative prognostic factor and increased mortality in pancreatic cancer. However, there are controversies regarding the effects of obesity on long-term post-operative results in the patient with pancreatic cancer.
 ...
PMID:[Obesity and pancreatic diseases]. 2228 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>