Chronic kidney disease is associated with a higher risk of kidney and urothelial cancer, but not other types of cancer, according to research being presented at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium in San Francisco. Urothelial cancers affect the bladder, ureters, and renal pelvis.
Researchers from Huntsman Cancer Institute at the University of Utah and Kaiser Permanente’s Northern California Division of Research found that higher risk for kidney cancer and urothelial cancer is associated specifically with chronic kidney disease as measured by a reduced flow rate of filtered fluid through the kidneys. The researchers found no significant associations with prostate, colorectal, lung, breast, or any other cancers.
‘We’ve known for some time that the incidence of chronic kidney disease continues to rise and that an estimated 11.5 percent of the United States population has reduced kidney function,’ said William T. Lowrance, MD, with Huntsman Cancer Institute and lead author of the research. ‘We also know from previous research that there are higher risks of cancer in people with end-stage renal disease requiring dialysis or transplantation.’
‘What we haven’t known is whether less severe kidney disease is independently associated with cancer,’ said Alan S. Go, acting director of the Kaiser Permanente Division of Research, and the senior author of the abstract being presented this week. ‘These findings describe an association that could have important public health implications for screening and early detection of cancer in the growing number of patients with chronic kidney disease.’
Researchers evaluated the association between chronic kidney disease and the risk of incident cancer in a large, diverse, community-based population linked to a regional cancer registry. As was hypothesised, they found an independent, graded increased risk of kidney cancer with lower estimated glomerular filtration rate, the flow rate at which the kidneys filter fluid. The study examined all people with measured kidney function who are receiving care within Kaiser Permanente Northern California, a large, integrated health care delivery system providing care to 3.2 million members. The Kaiser Permanente Cancer Registry links to the National Cancer Institute-sponsored Surveillance, Epidemiology, and End Results (SEER) Cancer Registry that collects detailed data on incident cancer site, initial treatment and other patient characteristics.
Research scientists adjusted for a large set of factors that may confound the relationship between level of kidney function and cancer risk. The risk of renal cancer retained a robust and graded association with renal function. As chronic kidney disease worsened, the risk of renal cancer increased, they explained. There was a similar association between estimated GFR and urinary tract (excluding prostate) cancer, although the magnitude of this association was less pronounced than observed with renal cancer, they added. Kaiser Permanent

In a genome-wide association (GWA) study, researchers from Boston University Schools of Medicine (BUSM) and Public Health (BUSPH) have identified several genes which influence degeneration of the hippocampus, the part of the brain most associated with Alzheimer disease (AD). The study demonstrates the efficacy of endophenotypes for broadening the understanding of the genetic basis of and pathways leading to AD.
AD is a progressive neurodegenerative disorder for which there are no prevention methods. Available drugs only marginally affect disease severity and progression, making AD effectively untreatable.
GWA studies using very large samples have increased the number of robust associations to 10 genes, including APOE. However, these genes account for no more than 35 percent of the inherited risk of AD and most of the genetic underpinning of the disorder remains unexplained. According to the researchers, magnetic resonance imaging (MRI) of the brain provides in vivo quantitative measures of neurodegenerative and cerebrovascular brain injury that may represent AD-related changes long before clinical symptoms appear. These measures are more powerful than comparisons of individuals with AD with cognitively healthy persons because they avoid misclassification of normal persons who will develop disease in the future.
BUSM researchers conducted a two-stage GWA study for quantitative measures of hippocampal volume (HV), total cerebral volume (TCV) and white matter hyperintensities (WMH). Brain MRI measures of HV, TCV and WMH were obtained from 981 Caucasian and 419 African-American AD cases and their cognitively normal siblings in the MIRAGE (Multi Institutional Research in Alzheimer’s Genetic Epidemiology) Study. In addition, similar MRI measures were obtained from 168 AD cases, 336 individuals with mild cognitive impairment and 188 controls (all Caucasian) in the AD Neuroimaging Initiative (ADNI) Study. The MIRAGE Caucasian families and ADNI subjects were included in the first stage and the MIRAGE African American families were added in stage two. Results from the two Caucasians data sets were combined by meta-analysis.
In stage two, one genetic marker (i.e. single nucleotide polymorphism or SNP) from each of the gene regions that were most significantly associated with AD in the Caucasian data sets was evaluated in the African-American data set.
Novel genome-wide significant associations were observed for HV with SNPs in the APOE, F5/SELP, LHFP, and GCFC2 gene regions. All of these associations were supported by evidence in each data set.
‘Our two-stage GWAS identified highly significant associations between a measure of degeneration in the brain region most strongly correlated with AD and several genes in both Caucasian and African American samples containing AD, cognitively impaired and cognitively healthy subjects. One of these associations was with the ε4 variant of APOE which is the most well-established genetic risk factor for AD. Other associations were demonstrated with markers in F5/SELP, LHFP, and GCFC2, genes not previously implicated in this disease’ explained senior author Lindsay Farrer, PhD, chief of biomedical genetics at BUSM. He also noted, ‘previous studies showed that blood level of P-selectin (the protein encoded by SELP) has been correlated with rate of cognitive decline in AD patients.’
Farrer believes it is very likely that the number and specificity of these associations will increase in future studies using larger samples and focused on additional precise structural and functional MRI measures. ‘These findings will inform experiments designed to increase our understanding of disease-causing mechanism and may lead to new therapeutics targets,’ added Farrer. Boston University Medical Center

Scientists have identified which strains of the Toxoplasma gondii parasite, the cause of toxoplasmosis, are most strongly associated with premature births and severe birth defects in the United States. The researchers used a new blood test developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to pinpoint T. gondii strains that children acquire from their acutely infected mothers while in the womb.
Pregnant women can become infected with T. gondii through contact with cat faeces that contain infectious forms of the parasite or by eating undercooked meat. Women who become infected while pregnant may miscarry, give birth prematurely, or have babies with eye or brain damage.
‘If undetected or untreated, congenital toxoplasmosis can have serious consequences for a child’s quality of life,’ noted NIAID Director Anthony S. Fauci, M.D. ‘The findings from this study support the value of screening for toxoplasmosis to identify patients who could benefit from treatment.’
Currently available blood tests can determine whether a person has ever been infected with any strain of Toxoplasma parasite. The experimental test developed at NIAID improves upon the older tests because it can detect the presence of strain-specific antibodies that distinguish infecting strains from one another. The test was developed by Michael Grigg, Ph.D., of NIAID’s Laboratory of Parasitic Diseases, and his colleagues. It was applied to blood samples collected between 1981 and 2009 as part of the National Collaborative Chicago-Based Congenital Toxoplasmosis Study. The study of congenitally infected children was initiated by NIAID grantee Rima McLeod, M.D., of the University of Chicago, who is the first author of the new study.
At least 15 distinct T. gondii strain types have been found throughout the world. In France, where research has been done to establish which strains are most common, a strain called type II predominates. Type II parasites can be distinguished from all other strains, which are collectively termed not exclusively type II strains (or NE-II).
Using the new test, the researchers found evidence of either type II or NE-II infections in 183 of the mother-child pairs in the national congenital toxoplasmosis study. Statistical analysis revealed that NE-II parasites were more likely to be associated with premature birth, and infants infected with these strains were more likely to have severe manifestations of disease than infants infected by type II parasites. For example, severe eye damage was seen in 67 percent of NE-II cases (59 out of 88), while such eye damage was present in only 39 percent of type II cases (18 out of 46). The researchers noted, however, that the association is not absolute, and that mild, moderate or severe disease can result regardless of the infecting strain.
‘We knew that, in mice, certain parasite strains are clearly associated with severe disease,’ said Dr. Grigg. ‘But we didn’t know if the same association between strain type and disease severity would hold true for people. Until now, we had not systematically determined whether infected people in the United States had European-type strains or other types, and we also hadn’t determined whether strains found here would have more severe disease symptoms associated with them.’
When she helped start the congenital toxoplasmosis study in 1981, optimal drug treatment regimens were unknown, said Dr. McLeod. Now, thanks in part to controlled clinical trials run under the auspices of the study, the condition can be successfully treated and many babies who are diagnosed before or shortly after birth and who are treated suffer few or no ill effects. When the researchers looked at the clinical histories of those children in the long-term study who had been diagnosed with congenital toxoplasmosis during gestation and whose mothers had received drug treatment prior to giving birth, the association between NE-II and severe disease at birth vanished. ‘Our study demonstrates that outcomes are equally good following postnatal treatment for type II and NE-II parasites, although not all outcomes are favorable for all children,’ she said.
In France, all pregnant women are screened for Toxoplasma infection. Prompt treatment is offered to any woman who becomes infected while pregnant, thus lessening the chance that the parasite will damage the fetus, Dr. McLeod noted. ‘In the United States, obstetrical screening for Toxoplasma infection is rarely practiced. This new study underscores the value of identifying all patients who will benefit from treatment and suggests that widespread screening and treatment of pregnant women who are infected could prevent infants from suffering eye and brain damage due to congenital toxoplasmosis,’ she said. EurekAlert

The study is the first to directly show how low testosterone levels in fat tissue can be instrumental in the onset of Type 2 diabetes.
Testosterone is present throughout the body. Low testosterone levels are linked to obesity, a known risk factor for diabetes. It acts on fat cells through molecules known as androgen receptors. These enable the testosterone to activate genes linked to obesity and diabetes.
The research showed that mice in which the function of testosterone in fat tissue was impaired were more likely to be insulin resistant than mice in which the role of testosterone was not hindered.
As men age their testosterone levels lower. This, along with increasing obesity, will increase the incidence of diabetes.
The findings from the University of Edinburgh could also help explain why older men are more at risk of developing diabetes, because testosterone levels fall in men as they age.
It showed that mice, which did not have androgen receptors in fat tissue for testosterone to attach to, were more likely to show signs of insulin resistance than other mice.
Researchers found that mice without androgen receptors in fat tissue also became fatter than other mice and developed full insulin resistance when both types were fed a high-fat diet.
The study showed that insulin resistance occurred in mice when the function of testosterone was impaired regardless of body weight.
Scientists believe that a protein called RBP4 plays a crucial role in regulating insulin resistance when testosterone is impaired. They found that levels of RBP4 were higher in mice in which the role of testosterone was impaired. The Edinburgh team say that its findings could lead to the development of new treatments that regulate production of RBP4. This could reduce the risk of diabetes in men with lower levels of testosterone.
Researchers are now planning to study patients with Type-2 diabetes to see if their levels of testosterone correlate with levels of RBP 4.
‘We already know that low testosterone levels are associated with increased obesity and therefore with increased risk of developing Type 2 diabetes, but this study provides evidence that there can be increased risk even when body mass is not affected. Yet while testosterone-impaired mice developed insulin resistance whatever diet they were given, the effect was considerably more pronounced on those fed on a high fat diet. This reinforces Diabetes UK advice that a healthy balanced diet is important for everyone and particularly for those already at high risk of developing Type 2 diabetes.’ says Dr Iain Frame, Director of Research at Diabetes UK. University of Edinburgh