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

Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but highly fatal. Gallstones represent the major risk factor for biliary tract cancer, and share with gallbladder cancer a female predominance and an association with reproductive factors and obesity. Although estrogens have been implicated in earlier studies of gallbladder cancer, there are no data on the role of androgens. Because intracellular androgen activity is mediated through the androgen receptor (AR), we examined associations between AR CAG repeat length [(CAG)(n)] and the risk of biliary tract cancers and stones in a population-based study of 331 incident cancer cases, 837 gallstone cases, and 750 controls from Shanghai, China, where the incidence rates for biliary tract cancer are rising sharply. Men with (CAG)(n) >24 had a significant 2-fold risk of gallbladder cancer [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.07-3.73], relative to those with (CAG)(n) < or = 22. In contrast, women with (CAG)(n) >24 had reduced gallbladder cancer risk (OR, 0.69; 95% CI, 0.43-1.09) relative to those with (CAG)(n) < or = 22; P interaction sex = 0.01, which was most pronounced for women ages 68 to 74 (OR, 0.48; 95% CI, 0.25-0.93; P interaction age = 0.02). No associations were found for bile duct cancer or gallstones. Reasons for the heterogeneity of genetic effects by gender and age are unclear but may reflect an interplay between AR and the levels of androgen as well as estrogen in men and older women. Further studies are needed to confirm these findings and clarify the mechanisms involved.
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PMID:Androgen receptor CAG repeat length and risk of biliary tract cancer and stones. 2020 Apr 39

Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps.
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PMID:Epidemiology of gallbladder disease: cholelithiasis and cancer. 2257 Jul 46

General obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested case-control subset. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87; p(trend) < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12-2.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations.
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PMID:Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort. 2261 81

Obesity has become a global health issue because of its increased morbidity and mortality, and a close association with at least 20 different cancers. Clinical and epidemiological studies have suggested that obesity and overweight are positively related with the risk of GBC. Gallbladder cancer (GBC) is a relatively infrequent but highly lethal neoplasm. Obesity may disturb lipid and endogenous hormones metabolism, affect gallbladder motility, increase the risk of gallstones, and thus plays a role in GBC. Control of obesity through measures such as lifestyle modification, healthy diet, and regular exercise may prove useful in the prevention of GBC.
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PMID:Association between obesity and gallbladder cancer. 2265 97

Currently, more than 14% of the world's population is pre-obese or obese. The percentage is even higher in developed countries. Obesity is an important risk factor for a vast number of nonmalignant and malignant digestive diseases. Some of the more important examples are cholelithiasis, nonalcoholic fatty liver disease, and gastroesophageal reflux disease on the one hand and esophageal adenocarcinoma, gastric cardia adenocarcinoma, pancreatic cancer, liver cancer, gallbladder cancer, and colorectal cancer on the other hand. Their epidemic trends as reported in recent studies are reviewed here. Knowledge of their dependencies on obesity will yield a deeper understanding which is necessary to improve prevention and treatment concepts of this epidemic.
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PMID:Epidemic trends of obesity with impact on metabolism and digestive diseases. 2272 28

Obesity is a fast-emerging epidemic in the Asia-Pacific region, with numbers paralleling the rising global prevalence within the past 30 years. The landscape of gut diseases in Asia has been drastically changed by obesity. In addition to more non-specific abdominal symptoms, obesity is the cause of gastro-oesophageal reflux disease, various gastrointestinal cancers (colorectal cancer, hepatocellular carcinoma, oesophageal adenocarcinoma, gastric cardia adenocarcinoma, pancreatic cancer and gallbladder cancer) and non-alcoholic fatty liver disease. Abnormal cross-talk between the gut microbiome and the obese host seems to play a central role in the pathogenesis, but more studies are needed.
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PMID:What is Obesity Doing to Your Gut? 2589 44

Persistent hepatic inflammation resulting from hepatitis B or C virus infections (HBV or HCV, respectively), obesity-associated non-alcoholic steatohepatitis (NASH) or alcohol abuse is a hallmark feature of chronic liver diseases and appears to be an essential prerequisite of hepatocarcinogenesis. The inflammatory processes in the liver are regulated by various chemokines, which orchestrate the interaction between parenchymal liver cells, Kupffer cells (resident macrophages), hepatic stellate cells (HSC), endothelial cells, and infiltrating immune cells. In consequence, these cellular interactions result in the re-modeling of the hepatic microenvironment toward a pro-inflammatory, pro-fibrotic, pro-angiogenic and thus pre-neoplastic milieu. Once developed, liver neoplasms provoke pro- and anti-tumor immune responses that are also critically regulated through differential activation of chemokine pathways. With respect to hepatobiliary cancers, including hepatocellular carcinoma (HCC), gallbladder cancer and cholangiocellular carcinoma (cholangiocarcinoma), together belonging to the highest causes of cancer-related deaths worldwide, this review article will give an overview of chemokine pathways involved in both the establishment of a pro-tumorigenic microenvironment as well as the development and progression of hepatobiliary cancer. Pharmaceutical targeting of chemokine pathways is a promising approach to treat or even prevent hepatobiliary cancer.
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PMID:Role of chemokine pathways in hepatobiliary cancer. 2612 64

Obesity is an increasingly common problem worldwide and a risk factor for a variety of gastrointestinal (GI) diseases, both non-neoplastic (e.g. gastro-oesophageal reflux and Barrett's oesophagus) and neoplastic (e.g. oesophageal adenocarcinoma, colorectal carcinoma, and gallbladder cancer). Furthermore, obesity is associated with worse GI cancer outcomes. Body mass index is a commonly used measure of fat accumulation, although specific patterns such as abdominal/central obesity and visceral fat quantity sometimes predict disease risk more accurately. Metabolic syndrome (MS) is a related condition characterized by central adiposity and insulin resistance. The reasons for the associations with neoplasia are diverse. Established cancer-related conditions that have a higher prevalence in overweight subjects include Barrett's oesophagus and gallstones. Preneoplastic lesions such as colorectal adenoma, colorectal serrated lesions and pancreatic intraepithelial neoplasia are also associated with obesity/MS. At the cellular level, adipocytes can release carcinogens such as adipokines, insulin-like growth factor, and vascular endothelial growth factor. Inflammatory cells constitute a further potential source of carcinogens; in obese subjects, their numbers are increased systemically and in adipose tissue. Animal studies have contributed additional information. For example, mice with a genetic predisposition to develop colorectal carcinoma given a high-fat diet have larger and more numerous intestinal adenomas than controls, and there may be demonstrably higher levels of mucosal oncogenic factors. The associations between obesity and GI disease are of variable strength, and the underlying mechanisms are incompletely understood, but it is clear that obesity and MS have a significant, potentially avoidable and often under-recognized impact on the population burden of GI disease.
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PMID:Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract. 2659 7

Emerging evidence has shown that leptin, an adipocyte-derived cytokine that is closely associated with obesity, play a significant role in carcinogenesis and tumorigenesis. However, its impact on gallbladder cancer (GBC) remains unclear. In this study, we firstly found that leptin and its functional receptor OB-Rb were significantly co-expressed in human GBC tissues and cell lines, the content of which were higher than those in normal human gallbladder tissues. Treatment with leptin promoted the proliferation, migration and invasion of GBC cells, which were attenuated by OB-Rb shRNA. Blocking in the G2/M period of cell cycle, increasing of MMP3 and MMP9, increasing of VEGF-C/D, activation of SOCS3/JAK2/p-STAT3 pathway was demonstrated after treatment with leptin. All of these positive responses were attenuated by OB-Rb receptor shRNA. Taken together, our findings suggest that leptin promoted the proliferation, migration and invasion of GBC cells by increasing OB-Rb expression through the SOCS3/JAK2/p-STAT3 signal pathway. Targeting the leptin/OB-Rb axis could be an attractive therapeutic strategy for treatment of GBC.
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PMID:Leptin promotes proliferation and metastasis of human gallbladder cancer through OB-Rb leptin receptor. 2721 17

Obesity is a known cause of gallstone formation and gallstones increases the risk of gallbladder cancer (GBC), but the relation of body mass index (BMI) to GBC remains incompletely understood. To help elucidate the role of obesity in GBC, we performed a meta-analysis of the relationship between BMI and GBC risk. PUBMED and EMBASE databases were searched up to April 17, 2016. Fifteen articles with 5902 cases were identified. Random-effects models and dose-response meta-analyses were used to pool study results. Compared to normal weight, the pooled relative risks (RRs) and the corresponding 95% confidence intervals (CI) of GBC for overweight and obesity is 1.10 (0.98-1.23) and 1.58 (1.43-1.75) respectively. The RRs and 95% CI of overweight and obesity in man are 0.98 (0.90-1.08) and 1.43 (1.19-1.71), while the corresponding RRs in woman are 1.29 (1.08-1.55) and 1.68 (1.41-2.00) when compared to normal weight. A nonlinear dose-response relationship between BMI and risk of GBC was found (P=0.001), and the risk increased by 4% for each 1 kg/m2 increment in BMI. When adjusted for sex, at the point of BMI=25 kg/m2, the RRs (95% CIs) for women and men were 1.13 (1.01-1.25) and 0.98 (0.90-1.07) respectively. The corresponding RRs (95%CIs) at the point of BMI=30 kg/m2 were 1.56(1.39-1.75) vs. 1.24(1.06-1.44). These results suggest that association of obesity and risk of GBC is stronger in woman. Furthermore, overweight is only associated with GBC in woman. A even stricter weight control might be necessary for woman to prevent GBC.
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PMID:The association between BMI and gallbladder cancer risk: a meta-analysis. 2724 20


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