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)

Barrett's metaplasia develops in 6-14% of individuals with gastroesophageal reflux. Barrett's adenocarcinomas are increasing in epidemic proportions for as yet unknown reasons, approximately 0.5-1% of patients with Barrett's will develop adenocarcinoma. Heartburn duration and frequency (but not severity), male gender, and Caucasian race are major risk factors for developing cancer. Obesity and smoking are weak risk factors. Survival is determined by depth of tumor invasion (stage). Once invasion of the muscularis propia occurs, the vast majority of patients will have developed widespread metastasis, even when clinical staging studies are negative. No currently available therapy results in prolonged survival once metastases develop. Thus, the more widespread use of effective surveillance strategies is the only currently available means for reducing the morbidity and mortality associated with Barrett's adenocarcinoma.
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PMID:Barrett's esophagus: clinical characteristics. 1213 12

A dramatic increase in the incidence of esophageal adenocarcinoma has occurred among men in the United States over the last two decades. The underlying reasons remain largely unknown, although the increasing prevalence of obesity likely plays a role. Most adenocarcinomas arise in a metaplastic epithelium termed Barrett's esophagus (BE) that develops in approximately 10% of persons who have chronic gastroesophageal reflux. Persons with BE are at high risk (0.5-1.0%/year) of progressing to cancer. In a cross-sectional study of 429 persons with BE, we evaluated the associations between increased body mass index, anthropometric measures, cigarette smoking, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and markers of increased risk, including aneuploidy, increased 4N fraction, loss of heterozygosity (LOH) of 17p and 9p alleles, and high-grade dysplasia (HGD). In logistic regression models adjusting for age, gender, NSAID use, and cigarette smoking, increasing waist:hip ratio was related to increasing risk of aneuploidy (trend P = 0.01), 17p LOH (trend P = 0.005), and 9p LOH (trend P = 0.007). The odds ratios comparing highest to lowest quartiles were 4.3 [95% confidence interval (CI), 1.2-15.6] for aneuploidy, 3.9 (95% CI, 1.3-11.4) for 17p LOH, and 2.7 (95% CI, 1.2-6.3) for 9p LOH. A nonsignificant trend was also observed for increased 4N fraction, whereas little association was found for HGD. Similar patterns of risk were noted for other anthropometric measures such as waist:thigh and abdomen:thigh ratios. There was no evidence that elevated body mass index increased risk of any of the biomarkers. Suggestive evidence also was found for a protective effect of NSAID use. The odds ratios for current users, compared with those who never used NSAIDs regularly, were 0.6 (95% CI, 0.3-1.4) for increased 4N, 0.6 (95% CI, 0.3-1.3) for aneuploidy, 0.3 (95% CI, 0.1-0.7) for 17p LOH, and 0.7 (95% CI, 0.4-1.2) for HGD. There was no association between NSAID use and risk of 9p LOH. We conclude that an abdominal distribution of body fat, which is more common in men and is termed male-pattern obesity, may be a strong predictor of risk of neoplastic progression among persons with BE and may account in part for the male predominance of BE and esophageal adenocarcinoma. We also conclude that NSAID use may reduce the risk of progression to cancer in this population. Prospective studies are needed to confirm these results.
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PMID:Nonsteroidal anti-inflammatory drug use, body mass index, and anthropometry in relation to genetic and flow cytometric abnormalities in Barrett's esophagus. 1216 28

XRCC1 (X-ray repair cross-complementing group 1) is a base excision repair protein that plays a central role in the repair of DNA strand breaks and base damage from a variety of endogenous and exogenous oxidants including tobacco smoke. One genetic polymorphism (G-->A, Arg-->Gln at codon 399) occurs within a poly(ADP-ribose) polymerase binding region and within the central breast cancer susceptibility gene 1 product COOH terminus domain of XRCC1. The variant 399Gln allele of XRCC1 has been associated with elevated biomarkers of DNA damage in human cells. We conducted an analysis of the Arg399Gln polymorphism in XRCC1 using genomic DNA, and questionnaire information from 309 cases of pancreatic adenocarcinoma and 964 controls that were part of a population-based, case-control study conducted in the San Francisco Bay Area between 1994 and 2001. We genotyped individuals using a mass spectrometry-based method. Because smoking and obesity are known and suspected pancreas cancer risk factors, and have been associated with DNA damage and oxidative stress in target tissues, we estimated odds ratios (ORs), interaction contrast ratios (ICRs), and 95% confidence intervals for the combined effects of XRCC1 genotype and smoking or body mass index (in kg/m(2)). We also assessed potential gene-gene interactions between polymorphisms in XRCC1 and CYP1A1, GSTT1, and GSTM1. We found little or no evidence for an association between XRCC1 genotype and pancreatic cancer among Caucasians, African-Americans, or Asians. There was evidence for interaction between XRCC1 399Gln and smoking that was stronger among women than men. Relative to never active or passive smokers with the Arg/Arg genotype, the age- and race-adjusted ORs and ICRs (95% confidence limits) for heavy smoking (>or=41 pack-years) were: for Gln/Gln or Arg/Gln genotypes [women OR = 7.0 (2.4, 21), ICR = 3.1 (0.03, 6.2); men OR = 2.4 (1.1, 5.0), ICR = 1.3 (-0.20, 2.8)]; and for the Arg/Arg genotype [women OR = 2.2 (0.73, 6.4); men OR = 1.5 (0.68, 3.2)]. Analyses of combined genotypes suggested an interaction between XRCC1 (Gln/Gln or Arg/Gln) and GSTT1/GSTM1-null/null among women but not among men. There was no evidence of interaction between XRCC1 genotype and body mass index. Our results suggest that the XRCC1 399Gln allele is a potentially important determinant of susceptibility to smoking-induced pancreatic cancer. Our findings, including stronger associations and interactions among women, require replication in additional study populations.
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PMID:A population-based study of the Arg399Gln polymorphism in X-ray repair cross- complementing group 1 (XRCC1) and risk of pancreatic adenocarcinoma. 1218 19

In postmenopausal women, the predominate steroid is estrone, and data have indicated that conversion of androgen to estrone is 2-3 times greater in women with endometrial cancer than in others. 2 studies of exogenous estrogens in postmenopausal women are summarized. In the 1st, 317 patients with adenocarcinoma were compared with matched controls with cervical, ovarian, and vulval neoplasms. 152 patients had estrogen therapy as compared with 54 controls, and calculations revealed the cancer risk as 4.5 times greater among patients than controls. The 2nd study concerned the use of conjugated estrogens. 94 patients with endometrial cancer and double that number of matched controls were examined. Conjugated estrogens had been used by 57% of patients and only 15% of controls. The data revealed an increased risk of 5.6 times in patients using estrogen for between 1 and 5 years, rising to 13.9 times greater risk after 7 or more years; and this relationship could not be explained by factors such as age, parity, obesity, or menopausal age. The chance of endometrial cancer in postmenopausal women not using estrogens is 1/100,000/year. In estrogen users, the level increases to between 4 and 8/100,000/year. More information is needed on effects of estrogens; they are valuable in relieving psychological symptoms, vasomotor instability, and, perhaps, mortality, osteoporosis, fractures, and vascular diseases after oophorectomy. These advantages have to be weighed against thromboembolism, coronary diease, strokes, and possible cancer; the benefits and risks are not easily calculated.
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PMID:Doubts about oestrogen therapy in postmenopausal women. 1225 12

A carefully taken history and clinical examination are necessary for assessing the relative benefits and risks of estrogen replacement therapy for an individual patient. The patient's weight, blood pressure and urine need to be checked. Benefits of estrogen replacement are seen in relation to vasomotor symptoms, atrophy of the genital tract, bone metabolism, psychological symptoms, libido, skin, and cardiovascular effects. Estrogens are contraindicated with a history of previous deep vein thrombosis, ischemic heart disease or carcinoma of the breast. Care needs to be taken with liver disease, hyperlipidemias, diabetes, gallbladder disease, gross obesity, or in heavy smokers. Progesterones should always be administered if the uterus is present to prevent endometrial hyperplasia and adenocarcinoma. When properly selected and carefully monitored, many women may be relieved of unnecessary suffering due to menopause.
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PMID:Estrogen replacement therapy: its benefits and risks. 1227 83

Incidence of adenocarcinoma of the oesophagus and gastric cardia is increasing in most developed countries and strongly associated with obesity and male gender. An underlying increase in the prevalence of gastro-oesophageal reflux has generally been postulated. We suggest that the increase in frequency of reflux and the 2 associated forms of cancer can be explained by growing abdominal pressure brought about by increasing central obesity, most common among men, and sedentary lifestyle, including car use. Abdominal pressure is further accentuated mainly in men by the shift in Western male dressing towards the general use of belts.
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PMID:Oesophageal adenocarcinoma: a paradigm of mechanical carcinogenesis? 1239 49

Incidence rates for esophageal adenocarcinoma have increased >350% since the mid-1970s. Rates for gastric cardia adenocarcinoma have also increased, although less steeply. This led to the initiation of large population-based case-control studies, particularly in the United States and Sweden, aimed at identifying risk factors for these cancers. Results have been emerging from these studies, with the consistent finding that obesity and gastroesophageal reflux disease are important risk factors for these cancers. Analyses of dietary factors are also available and indicate that diets high in total fat, saturated fat and cholesterol are associated with an increased risk of these cancers, whereas several nutrients, particularly those found in plant foods (fiber, vitamin C, beta-carotene, folate), are associated with a reduced risk. Considering the incidence trends of these cancers and the trends in the prevalence of risk factors, the increasing prevalence of obesity in the United States likely accounts for some of the increased incidence. However, other contributors to the increasing trends have been suggested and will be discussed. Because diet, obesity and gastroesophageal reflux disease may not act independently in contributing to these cancers, current research is attempting to identify associations between the three risk factors and potential mechanisms of action to better understand the etiology of these cancers.
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PMID:Diet, obesity and reflux in the etiology of adenocarcinomas of the esophagus and gastric cardia in humans. 1242 72

Adenocarcinoma of the esophagus and the gastroesophageal junction is the twentieth most common malignancy in the United States. In developed countries, the incidence of esophageal adenocarcinoma is increasing 5% to 10% per year. Despite the use of endoscopy for earlier detection, mortality from esophageal adenocarcinoma has not declined. Using an evidence-based approach, we review screening methods for esophageal adenocarcinoma, including the use of a symptom questionnaire, identification of patients with a family history of Barrett's esophagus, peroral or transnasal endoscopy, barium swallow, fecal occult blood testing, and brush and balloon cytology. Screening has not been shown to reduce rate of progression of Barrett's esophagus to esophageal cancer. Many treatment options for dysplastic Barrett's esophagus or early carcinoma appear effective, but long-term follow-up data are not available. There is currently insufficient evidence supporting population-based screening for Barrett's esophagus. Several risk factors, including severe reflux symptoms, male sex, and obesity, may identify patients with gastroesophageal reflux disease who are at the greatest risk of the development of cancer.
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PMID:Screening for esophageal adenocarcinoma: an evidence-based approach. 1242

To evaluate the evidence for the role of weight control and physical activity in cancer prevention and to identify priorities for research and for public health action in relation to the primary prevention of cancer, an international working group of experts was convened in Lyon in February 2001 by the International Agency for Research on Cancer of the World Health Organization. The expert group concluded that limiting weight gain during adult life, thereby avoiding overweight and obesity, reduces the risk of postmenopausal breast cancer and cancers of the colon, endometrium, kidney (renal cell) and esophagus (adenocarcinoma). Limiting weight gain possibly reduces risk of cancer of the thyroid. Weight loss among overweight or obese persons possibly reduces risks of these cancers, but no definite conclusion can be drawn because of the paucity of the epidemiological evidence. The working group also concluded that there was sufficient evidence for the role of physical activity in preventing colon and breast cancers, and limited evidence for the cancers of the prostate and endometrium. Some of these effects were independent of that of the weight control. Taken together, the working group considered that excess body weight and physical inactivity account for approximately a quarter to one-third of cancers of the colon, breast, endometrium, kidney (renal cell) and esophagus (adenocarcinoma). Thus adiposity and physical inactivity appear to be the most important avoidable causes of these cancers.
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PMID:Weight control and physical activity in cancer prevention: international evaluation of the evidence. 1257 Mar 41

Resistin, a product of white adipose tissue, is postulated to induce insulin resistance in obesity and regulate adipocyte differentiation. The aim of this study was to examine resistin gene expression in adipose tissue from mice bearing the MAC16 adenocarcinoma, which induces cancer cachexia with marked wasting of adipose tissue and skeletal muscle mass. MAC16-bearing mice lost weight progressively over the period following tumour transplantation, while the weight of control mice remained stable. Leptin mRNA in gonadal fat was 50 % lower in MAC16 mice than in controls (p < 0.05). Plasma insulin concentrations were also significantly lower in the MAC16 group (p < 0.05). However, resistin mRNA level in gonadal fat in MAC16 mice was similar to controls (94 % of controls). Thus, despite severe weight loss and significant falls in leptin expression and insulin concentration, resistin gene expression appears unchanged in white adipose tissue of mice with MAC16 tumour. Maintenance of resistin production may help inhibit the formation of new adipocytes in cancer cachexia.
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PMID:Weight loss in tumour-bearing mice is not associated with changes in resistin gene expression in white adipose tissue. 1266 Aug 81


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