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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilms' tumor is a childhood kidney tumor that is a striking example of the way that cancer may arise through development gone awry. A proportion of these tumors develop as a result of the loss of function mutations in the Wilms' tumor suppressor gene, WT1. Inherited mutations in the WT1 gene can lead to childhood kidney cancer, severe gonadal dysplasia, and life-threatening hypertension. Knockouts show that the gene is essential for the early stages of kidney and gonad formation. These tissues are completely absent in null mice. The WT1 gene encodes numerous protein isoforms, all of which share four zinc fingers. There is a large body of evidence supporting the notion that WT1 is a transcription factor, particularly a transcriptional repressor. Recently, however, we obtained evidence that WT1 colocalizes and is physically associated with splice factors. What is more, one alternative splice isoform of WT1 containing three amino acids, Lys-Thr-Ser (KTS; inserted between zinc fingers 3 and 4) is preferentially associated with splice factors, whereas the other alternative splice version, lacking these three amino acids, preferentially associates with the transcriptional apparatus. Both genetic and evolutionary considerations suggest that these two different forms of the protein have different functions. We will discuss recent evidence to further implicate WT1 in splicing. Our results raise the possibility that regulation of splicing is a crucial factor in the development of the genitourinary system, and that tumors may arise through aberrant splicing. To pursue the regulation and function of WT1 in whole animals, we have been introducing the human gene and large flanking regions cloned in yeast artificial chromosomes directly into mice. These studies have allowed us to dissect the function of WT1 at late as well as at early stages in organogenesis and to identify new sites and surprising new potential functions for the gene.
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PMID:Multiple roles for the Wilms' tumor suppressor, WT1. 1019 91

Many cross-sectional and follow-up studies of large numbers of patients with hypertension have demonstrated an increased prevalence and mortality from renal cancer. We report the details of three patients with renal cell carcinoma from a series of 254 consecutive patients with malignant phase hypertension, an excess over the expected number reported from several large published series with non-malignant hypertension. In view of this excess we investigated the prevalence of hypertension in a series of 192 consecutive patients who presented with a diagnosis of renal cell carcinoma, in comparison with a local unselected population screening survey. Hypertension was found in 43% of the renal carcinoma patients and 20% of the local population, also a clear excess. The mechanism of the association between renal cancer and malignant and non-malignant hypertension is unclear.
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PMID:Renal cell carcinoma and malignant phase hypertension. 1133 28

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

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 shown to increase the risk or be associated with numerous conditions from cardiovascular disease and type II diabetes to erectile dysfunction and osteoarthritis. Obesity may also be associated with numerous cancers, and kidney cancer or renal-cell cancer (RCC) may have one of the strongest correlations to obesity compared with cancer at any other site. Almost every epidemiologic investigation has demonstrated an association that tends to affect women more than men, but both genders are impacted. In general, past studies suggest that with increasing weight, a threshold point exists whereby a certain range of body mass index dramatically changes risk. Men and women at the most extreme ends of obesity tend to have the highest risk or only risk in past studies. Individuals at the more extreme ends of obesity may be affected by an almost indefinite number of mechanisms and exposures that could determine incidence and possibly prognosis. For example, higher estrogen levels, elevated insulin levels, a greater concentration of growth factors in adipose tissue, hypertension, cholesterol metabolism abnormalities, and immune malfunction are just some of the potential mechanisms that may increase kidney cancer risk. Obese individuals may also have lower serum levels of vitamin D and engage in less physical activity. Smoking or genetic predisposition to RCC may synergistically contribute to the effect of obesity on risk. The potential mechanisms and associations are numerous and complex. Regardless of the actual cancer risk now and in the future, the overall effect of obesity on general health is clear, and this should be kept in mind in the discussion between health professional and patient.
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PMID:Obesity, interrelated mechanisms, and exposures and kidney cancer. 1176 79

Obesity, which has reached epidemic proportions in the United States and other western countries, may be complicated by hypertension, an increased incidence of renal cancer or proteinuria. Patients with obesity-associated proteinuria show focal glomerulosclerosis and glomerulomegaly on biopsy, usually have minimal clinical edema and relatively normal levels of serum albumin, cholesterol and blood pressure, and can progress to end-stage renal disease. Severe obesity may also be an additive risk factor in patients with preexisting nephropathy or reduced renal mass. The pathophysiology of obesity-associated proteinuria is unclear but may include hyperfiltration, increased renal venous pressure, glomerular hypertrophy, hyperlipidemia and increased synthesis of vasoactive and fibrogenic substances, including angiotensin II, insulin, leptin and transforming growth factor-beta1. These substances may individually or interactively affect glomerular hyperfiltration, mesangial cell hypertrophy and matrix production, and the production of collagen, fibronectin, transforming growth factor-beta and other fibrogenic mediators of change. Although angiotensin-converting enzyme inhibition has proven to have an impact, perhaps temporarily, on obesity-associated proteinuria in humans, weight reduction early in the course of the disease would appear the most important therapeutic approach.
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PMID:Obesity and renal disease. 1198 Dec 64

Multiple studies have noted that obese individuals are at a high risk of renal cell cancer. Similarly, numerous case-control and cohort studies have consistently reported that individuals with a history of hypertension experience an increased risk of renal cancer. In spite of this compelling body of epidemiologic data, no credible hypothesis has been advanced to explain this dual etiologic association. In this communication we propose that lipid peroxidation, which is increased in obese and hypertensive subjects, is the mechanism responsible, at least in part. for their increased risk of renal cell carcinoma. In experimental animals lipid peroxidation of the proximal renal tubules is a necessary mechanistic pathway in renal carcinogenesis induced by several different chemicals. Our hypothesis may also explain the roles of other risk (oophorectomy/hysterectomy, parity, smoking, diabetes) and protective factors (dietary antioxidants) for renal cell cancer.
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PMID:Lipid peroxidation: a novel and unifying concept of the etiology of renal cell carcinoma (United States). 1202 Jan 11

Kidney cancer remains relatively rare, but incidence and mortality rates are reported to be rising steadily across the world. To determine if such increases were occurring in the UK, we examined the rates of incidence and mortality in different histological subtypes of kidney cancer in the Northern and Yorkshire region of England. Details of all 8741 cases diagnosed between 1978 and 1997 were extracted from the population-based Northern and Yorkshire Cancer Registry. For all types of tumour, both incidence and mortality rates increased over the study period. Overall age-standardised incidence rates increased by 86% for renal parenchymal carcinoma (RPC) (80% for males, 90% for females) from 2.8 to 5.2 cases per 100000 (3.8-6.8 male, 2.0-3.8 female). There were incidence increases in all age groups, all Carstairs index groups and in both urban and rural populations. Although increased incidental detection of kidney tumours by improved investigational techniques may account for some of this rise, we believe it unlikely that it accounts for all of the increase observed. Potential aetiological causes for the increased rates include hypertension, smoking, a diet lacking fruit and vegetables, analgesic use and, particularly, obesity.
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PMID:Increased incidence of renal parenchymal carcinoma in the Northern and Yorkshire region of England, 1978-1997. 1270 65

The objective of this study was to determine the site-specific cancer incidence of hypertensive patients and examine the effect of blood pressure-related variables on the risk of cancers with elevated incidence among the hypertensive patients. A record linkage study of Hypertension Register of the North Karelia Project and the Finnish Cancer Registry was conducted. The mean follow-up time was 16 years. A total of 20 529 hypertensive patients were studied. Main outcome measures were standardised incidence ratios and hazard ratios. The overall cancer incidence was close to that of the general population for both men and women. The incidence rate for the kidney cancer was significantly increased in hypertensive patients (standardised incidence ratio 1.34, 95% confidence interval (CI) 1.11-1.60), as well as incidence rates for cancers of pancreas (1.26, 1.02-1.54), and endometrium (1.22, 1.01-1.44) in hypertensive women. The incidence of lung cancer was significantly decreased (0.86, 0.77-0.95). The incidence of liver cancer was elevated with borderline significance (1.36, 0.99-1.82). In Cox regression models, the use of antihypertensive drugs at baseline was a significant predictor of kidney (hazard ratio for use of antihypertensive drugs 1.89, 95% CI 0.96-3.75) and pancreatic cancer (1.78, 0.99-3.22) in women but not in men. The incidence of endometrial cancer or liver cancer was not related to blood pressure levels or the use of antihypertensive drugs. In women, obesity was a significant predictor of cancers of the endometrium, kidney and liver. In conclusion, increased occurrence of some cancer types among hypertensive patients seem to be partly explained by obesity and the use of antihypertensive drugs.
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PMID:Cancer pattern among hypertensive patients in North Karelia, Finland. 1570 72

Malignant kidney tumors account for approximately 2% of all new primary cancer cases diagnosed in the United States, with an estimated 30,000 cases occurring annually. Although a variety of agents, chemical and biological, have been implicated as causal agents in the development of renal cell carcinoma (RCC), the etiology remains enigmatic. The strongest association has been developed between cigarette smoking and renal cancer however consistent, positive associations between RCC and obesity, diabetes, and hypertension have also been reported. In addition, more recent investigations of familial kidney cancer syndromes indicate that a strong genetic component contributes to RCC development. Several genes have been identified through investigation of familial kidney cancer syndromes. This review article describes recent trends in RCC incidence and the currently identifiable etiological causes that account for approximately half of the RCC cases diagnoses. The remainder of this review then focuses on additional risk factors that have thus far not been well examined but may be helpful in explaining the increasing incidence trends and the geographic or racial variation observed nationally and worldwide.
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PMID:Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. 1594 10


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