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

Renal cell carcinoma (RCC), although occurring less frequently than prostate and bladder cancer, is actually the most malignant urologic disease, killing >35% of affected patients. Therefore, investigation of the nature of premalignant lesions of the kidney is a relevant issue. Following the most recent histological classification RCC can be subdivided into four categories: conventional RCC; papillary RCC; chromophobe RCC; and collecting duct carcinoma. In contrast to many genitourinary malignancies, premalignant alterations in the kidney are scarcely described. Intratubular epithelial dysplasia has been recognized as the most common precursor of RCC. In analogy to prostatic intraepithelial neoplasia (PIN), the premalignant lesions of the kidney are described as high or low-grade renal intratubular neoplasia. In contrast, precancerous lesions have been described as part of the von Hippel-Lindau syndrome (VHL) where the evolution from a simple cyst to an atypical cyst with epithelial hyperplasia to cystic or solid conventional-type RCC is well documented. Finally, in the genesis of papillary RCC an adenoma-carcinoma sequence has been recognized with specific genetic changes. There are no data on the epidemiology of premalignant lesions of the kidney, but research into the etiology of RCC has been extended substantially. Familial and genetic factors are well documented in VHL disease, in hereditary papillary RCC, in the tuberous sclerosis complex and in familial RCC. Cigarette smoking and obesity are established risk factors for RCC. Hypertension or its medication has also been associated with an increased risk. Among dietary factors an inverse relation between risk and consumption of vegetables and fruit has been found. Occupational exposure to substances such as asbestos and solvents has been linked to an increased risk of RCC. Specific RCC variants have distinctive chromosome alterations and several genes have been implicated in the development of RCC. Loss of material from the 3p chromosome characterizes conventional RCC and the deletion of the VHL suppressor gene plays an important role in the genesis of this RCC variant. In contrast, numerical changes with trisomy of chromosomes 7 and 17 and loss of the sex chromosome are typical changes in papillary tumors, whereas papillary RCC have additional trisomies. Chromophobe RCC is characterized by loss of chromosomes with a combination of monosomies. Less consistent genetic alterations are associated with collecting duct carcinoma. The traditional treatment of RCC is surgery by radical or partial nephrectomy. The latter approach carries a risk of tumor recurrence as a result of unrecognized satellite lesions or premalignant lesions that might have been present at the time of surgery. However, the reported recurrence rates after partial nephrectomy are <1% and therefore the possible presence of premalignant disease does not alter the actual treatment strategy advocated. Although multifocality and bilateral occurrence of RCC are much more likely in cases of papillary RCC, biopsy of the renal remnant or contralateral kidney is not justified even in patients with this tumor type. Conversely, patients with RIN in a partial or radical nephrectomy specimen or in a renal biopsy taken for whatever reason should be subjected to closer follow-up with regularly repeated ultrasound. When an effective chemopreventive regimen becomes available it might be useful for patients with an inherited risk of RCC as well as in those who are at risk of tumor recurrence after intervention. Mass screening with the purpose of detecting RCC at its earliest stage is not recommended at the present time, but screening focused on certain risk groups can be advocated. Further research is needed to identify avoidable risks, develop effective chemoprevention and recognize patients at risk.
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PMID:Precancerous lesions in the kidney. 1114 93

In the last decades incidence rates for renal cell carcinoma have been constantly increasing, especially in western European and Scandinavian countries and North America. Several epidemiological studies observed an increased relative risk of this tumour linked with some exogenous and/or environmental factors. The following exposures have been more consistently associated with renal cell carcinoma: tobacco smoking; occupational exposures (asbestos, aromatic hydrocarbons, chemical solvents); dietetic factors such as high energy intake, consumption of fried meats and poultry, and reduced intake of fruit and vegetables; iatrogenic factors such as analgesics and amphetamines; common diseases like obesity and hypertension. An effective preventive strategy for renal cancer could be carried out reducing the exposure to such risk factors.
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PMID:[Exogenous risk factors for parenchymal carcinoma of the kidney]. 1150 15

Peroxisome proliferator activated receptor gamma (PPARgamma) is a nuclear hormone receptor that has been shown to regulate differentiation and cell growth. Studies of the differentiative effects of PPARgamma agonists on several cancer cell lines led to the hypothesis that dysfunction of PPARgamma contributes to tumorigenesis. These functional observations were strengthened by genetic evidence: somatic loss-of-function mutations in PPARG, encoding PPARgamma, in sporadic colorectal carcinomas and somatic translocation of PAX8 and PPARG in follicular thyroid carcinoma. Recently overrepresentation of the H449H variant was found in a cohort of American patients with glioblastoma multiforme. The glioblastoma multiforme data suggest that PPARG contributes common, low-penetrance alleles for cancer susceptibility. To test this hypothesis in a broader range of cancers we examined a series of carcinomas of the cervix, endometrium, ovary, prostate, and kidney for germline sequence variation in PPARG. In addition to the two common sequence variants, P12A and H449H, there were five other sequence variants. P12A alleles were underrepresented in renal cell carcinoma patients compared to country-of-origin race-matched controls (3.75% vs. 12.1%, P<0.04). In contrast, the H449H variant was overrepresented in individuals with endometrial carcinoma compared to controls (14.4% vs. 6.25%, P<0.02). These observations lend genetic evidence consistent with our hypothesis that PPARG serves as a common, low-penetrance susceptibility gene for cancers of several types, especially those epidemiologically associated with obesity and fat intake.
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PMID:Opposite association of two PPARG variants with cancer: overrepresentation of H449H in endometrial carcinoma cases and underrepresentation of P12A in renal cell carcinoma cases. 1151 19

Few analytical epidemiological studies have investigated family history (FH) of urinary tract cancers as a potential risk factor for renal cell carcinoma (RCC). A population-based case-control study involving 550 non-Asian RCC patients 25 to 74 years of age and an equal number of sex-, age-, and race-matched neighborhood controls was conducted in Los Angeles, California. Detailed information on FH of cancer, medical and medication histories, and other life-style factors was obtained through in-person interviews. Having a first-degree relative with kidney cancer was associated with a significantly increased risk of RCC [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.04-5.9] after adjustment for potential confounding factors. Having a first and/or second-degree relative with kidney cancer was similarly associated with an increased risk of RCC (OR, 2.9; 95% CI, 1.4-6.3). Risk factors for RCC identified in the Los Angeles study include cigarette smoking, chronic obesity, history of hypertension, regular use of analgesics and amphetamines, intake of cruciferous vegetables (protective), and history of hysterectomy. None of the above risk factor-RCC associations differed significantly between RCC cases with and without a FH of kidney cancer. A FH of urinary tract cancers other than kidney cancer was not associated with RCC risk (OR, 0.7; 95% CI, 0.3-1.7). A FH of nonurinary tract cancers also was unrelated to RCC risk (OR, 1.1; 95% CI, 0.9-1.5).
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PMID:Family history and risk of renal cell carcinoma. 1153 54

Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies examining body weight in relation to kidney cancer, available in MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to studies assessing obesity as body mass index (BMI, kg m(-2)), or equivalent. The risk estimates and the confidence intervals were extracted from the individual studies, and a mixed effect weighted regression model was used. We identified 22 unique studies on each sex, and the quantitative analysis included 14 studies on men and women, respectively. The summary relative risk estimate was 1.07 (95% CI 1.05-1.09) per unit of increase in BMI (corresponding to 3 kg body weight increase for a subject of average height). We found no evidence of effect modification by sex. Our quantitative summary shows that increased BMI is equally strongly associated with an increased risk of renal cell cancer among men and women.
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PMID:Obesity and renal cell cancer--a quantitative review. 1159 70

Renal cell cancer (RCC) is responsible for a small percentage of total cancer cases and deaths throughout the world, but the incidence rates of RCC have been steadily increasing over the past decade, whereas numerous other cancers have stabilized or even decreased in number. Even in countries that were observed to have a lower incidence of this disease many are now experiencing large increases in the rates of this cancer. Most kidney cancers are RCC, and blacks are currently experiencing RCC rates that are higher than any other race. Older individuals are also at a higher risk compared with young individuals, but this observation may also be changing. The reasons for these potential increases are not understood beyond the partial impact and greater use of newer diagnostic procedures. Other reasons for higher rates of RCC and a better understanding of which individuals may be at the highest risk need to be examined to provide the clinician with possible clues as to who should be tested and what prevention measures should be offered. Most of the past investigations into risk factors have been case-control or retrospective studies, but some generalizations can still be made. Family history and genetics seem to increase risk, but overall are responsible for a small number of the total cases. Smoking, obesity, and even hypertension seem to be risk factors for RCC. Reducing these behaviors and conditions may also reduce the risk of RCC. Healthier eating habits (fruits and vegetables, and a lower caloric intake) and more physical activity may also reduce the risk of RCC. Therefore, it is possible that the increases in RCC may also be due, in part, to unhealthy lifestyle factors that have been on the increase over the past several decades. Recommendations for cardiovascular disease prevention should also be applied to patients or clinicians concerned about RCC risk. Finally, numerous occupations, occupational exposures, reproductive and hormonal changes or manipulations, and a variety of other factors may impact risk, but overall their contribution seems small compared with other more consistent risk factors.
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PMID:Review of potential risk factors for kidney (renal cell) cancer. 1176 80

Recently, several epidemiologic observations have suggested that obesity might be an independent risk factor for certain malignancies such as breast cancer, colon cancer, renal cell carcinoma, and esophageal adenocarcinoma. However, there are no studies examining the risk of hepatocellular carcinoma (HCC) in obesity. The aim of the present study was to determine whether obesity is an independent risk factor for HCC in patients with cirrhosis. Explanted liver specimens from a national database on patients undergoing liver transplantation were examined for HCC, and the incidence was compared among patients with varying body mass indices according to the etiology of cirrhosis. A multivariate analysis was used for controlling other potentially confounding variables such as age and sex. Among 19,271 evaluable patients, the overall incidence of HCC was 3.4% (n = 659) with a slightly higher prevalence among obese patients compared with lean patients. Obesity was an independent predictor for HCC in patients with alcoholic cirrhosis (odds ratio [OR], 3.2; 95% CI, 1.5-6.6; P =.002) and cryptogenic cirrhosis (OR, 11.1; 95% CI, 1.5-87.4; P =.02). Obesity was not an independent predictor in patients with hepatitis C, hepatitis B, primary biliary cirrhosis, and autoimmune hepatitis. The higher risk of HCC in obese patients is confined to alcoholic liver disease and cryptogenic cirrhosis. In conclusion, more frequent surveillance for HCC may be warranted in obese patients with alcoholic and cryptogenic cirrhosis. However, as this study is based on patients with advanced cirrhosis, our findings need to be confirmed in a broader population of individuals with cirrhosis.
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PMID:Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? 1208 59

Although renal cell carcinoma accounts for only 3% of adult malignancies, it has been increasing in incidence by 2-4% per year since the 1970's. Cigarette smoking, obesity and end-stage renal disease are important risk factors. Genetic syndromes such as von Hippel-Lindau disease are also associated with an increased incidence of renal cell carcinoma. Localized disease should be treated with surgical resection. However, approximately 30% of patients present with metastatic disease. Complete resection of metastases can result in long-term survival in some individuals. Removal of the primary renal tumor in patients with unresectable disseminated disease has also been shown to improve survival in selected good performance status patients receiving systemic immunotherapy. While chemotherapy has been relatively ineffective in the treatment of renal cell carcinoma, biologic therapy with interleukin-2 or interferon does lead to responses in a minority of patients, with occasional long-term survivors. Recently, promising results have been reported with allogeneic stem cell transplantation using a non-myeloablative conditioning regimen. However, therapy for metastatic renal cell carcinoma remains inadequate. Ongoing trials with novel approaches such as anti-angiogenesis agents, cyclin-dependent kinase inhibitors, and tumor vaccines will hopefully lead to improved outcomes in this disease.
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PMID:Renal cell carcinoma: current status and future directions. 1260 28

The granulin-epithelin precursor, progranulin, PC-cell-derived growth factor or acrogranin, is a high molecular weight secreted mitogen. It is abundantly expressed in rapidly cycling epithelial cells, in the immune system and in neurons, such as cerebellar Purkinje cells. Progranulin contributes to tumorigenesis in diverse cancers, including breast cancer, clear cell renal carcinoma, invasive ovarian carcinoma and glioblastoma. It regulates the rate of epithelial cell division in responsive epithelial cells, and confers an invasive phenotype on these cells. It is involved in the wound response. During embryogenesis, progranulin accelerates blastocyst formation, and is a growth factor for trophectodermal cells. In the neonate, progranulin, regulates the hormone-dependent virilization of the hypothalamus. It activates phosphorylation of Shc, and p44/42 MAPK (mitogen activated protein kinase) in the ERK (extracellular regulated kinase) signaling pathway; PI3K (phosophatidyl inositol-3-kinase), AKT/protein kinase B, and p70S6kinase in the phosophatidyl inositol-3-kinase pathway; and focal adhesion kinase in the adhesion/motility pathway. The signaling properties of progranulin are apparently similar to those of classic growth factors, but the functional properties of progranulin distinguish it from these molecules. Deleting the insulin-like growth factor I receptor from murine embryonic fibroblasts blocks proliferation in response to all classic growth factors, such as epidermal growth factor, or platelet-derived growth factor, whereas progranulin retains mitotic activity on these cells. The defined biological actions of progranulin probably represent a small fraction of its overall functions. Transcriptome analyses show that the progranulin gene is induced in numerous situations that vary from obesity to the transcriptional response of cells to antineoplastic drugs. Here, the biological roles of progranulin will be reviewed, with an emphasis on cancer and cell proliferation.
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PMID:Progranulin (granulin-epithelin precursor, PC-cell derived growth factor, acrogranin) in proliferation and tumorigenesis. 1297 94

Limited data exist regarding whether a history of urinary tract infection (UTI) increases risk of developing renal cell carcinoma (RCC). Furthermore, it is unclear whether any association of RCC with a history of UTIs is modified by known risk factors for RCC (i.e., smoking, obesity). The authors report data from a 1986-1989 population-based case-control study in Iowa. RCC cases (233 males, 139 females) were identified through the Iowa Cancer Registry; controls (1,497 males, 751 females) were randomly selected from the general population, frequency matched on age and sex. Subjects provided detailed information on demographic, anthropometric, lifestyle, dietary, and medical history risk factors. In age-adjusted analysis, risk increased for subjects who self-reported a history of physician-diagnosed kidney or bladder infection (odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.5, 2.5) compared with those reporting no such history. Both sex and smoking status modified the risk of RCC associated with a history of UTI, with the strongest risk reported for males (OR = 2.7, 95% CI: 1.9, 3.8) and current smokers (OR = 4.3, 95% CI: 2.7, 6.7). The strongest risk was reported for male current smokers with a history of UTI (OR = 9.7, 95% CI: 5.0, 18.1). Multivariate adjustment for anthropometric, lifestyle, and dietary factors did not alter these findings. Results suggest a positive association of UTI history with RCC development, with elevated risks most notable for males with a history of smoking.
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PMID:History of urinary tract infection and risk of renal cell carcinoma. 1469 58


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