Polymorphisms in GSTT1, GSTM1, NAT1 and NAT2 genes and bladder cancer risk in men and women

Background: Cigarette smoking is an established risk factor for bladder cancer. Epidemiological and biological data suggest that genetic polymorphisms in activating and detoxifying enzymes may play a role in determining an individual's susceptibility to bladder cancer in particular when in combination with specific environmental exposures such as cigarette smoking. N-acetyltransferase (NAT) enzymes, NAT1 and NAT2, are involved in the activation and detoxification of tobacco smoke constituents. Polymorphisms in these genes alter the ability of these enzymes to metabolize carcinogens, as certain allelic combinations result in a slow or rapid acetylation phenotype. Glutathione S-transferases (GSTs) also detoxify tobacco smoke constituents, and polymorphisms within the GSTM1 and GSTT1 genes can result in a complete lack of enzyme activity. Methods: We assessed the association between common polymorphisms identified in the GSTM1, GSTT1, NAT1, and NAT2 genes and the risk of bladder cancer in two nested case-control studies within the Nurses' Health Study (n = 78 female cases, 234 female controls) and the Health Professionals' Follow-up Study (n = 139 male cases, 293 male controls). We also evaluated whether cigarette smoking modified the associations of the genotypes and bladder cancer risk in men and women. Results: Overall, we observed no statistically significant associations between the polymorphisms and bladder cancer risk among men and women, although given our sample size, we had limited power to detect small to moderate effects. There was however the suggestion of an increased risk among female ever smokers with the NAT2 slow genotype and an increased risk in male never smokers with the GSTM1 null genotype. Conclusion: In summary, these prospective results are consistent with previous literature supporting associations between bladder cancer and the NAT2 slow acetylation and the GSTM1 null genotypes

Intestinal Behçet and Crohn’s disease: two sides of the same coin

Abstract Behçet’s disease (BD) and Crohn’s disease (CD) are chronic immune-mediated, inflammatory disorders affecting many different systems (joints, skin, eyes, gastrointestinal and biliary tracts). Both disorders have fluctuating courses and when gastrointestinal symptoms are prevalent, differential diagnosis can be difficult. BD involves the gastrointestinal tract in 10–15% of cases with localized lesions in the ileocecal region. The clinical picture is heterogeneous with various clusters of disease expression. CD is a chronic inflammatory disorder, which can affect any part of the intestinal tract, as well as extra-intestinal tissue. Factors that contribute towards the pathogenesis of both disease include the host’s genetic profile, and immune system, and environmental factors such as the gut microbiota. The aim of this manuscript is to provide a narrative review of clinical features of BD and CD, highlighting the importance of differential diagnosis and therapeutic approach, especially in the presence of gastrointestinal involvement. A comprehensive search of published literature using the Pubmed ( http://www.ncbi.nlm.nih.gov/pubmed/ ) database was carried out to identify all articles published in English from 1999 to October 2016, using 4 key terms: “Behçet Disease”, “Intestinal Behçet’s Disease”, “Crohn’s Disease” and” Inflammatory Bowel Disease”

Dense deposit disease in a child with febrile sore throat

Dense deposit disease or membranoproliferative glomerulonephritis type II is a rare glomerulopathy characterized on renal biopsy by deposition of abnormal electron-dense material in the glomerular basement membrane. The pathophysiologic basis is uncontrolled systemic activation of the alternate pathway of the complement cascade. C3 nephritic factor, an autoantibody directed against the C3 convertase of the alternate pathway, plays a key role. In some patients, complement gene mutations have been identified. We report the case of a child who had persistent microscopic hematuria, proteinuria, and hypocomplementemia C3 for over 2 months. Renal biopsy confirmed the diagnosis of dense deposit disease

Clinical Evaluation of Percutaneous Vertebroplasty in a Patient with Paraplegia and Immobilization Syndrome: A Case Report

We will discuss a potential role of percutaneous vertebroplasty (PVP) in the management of a patient with immobilization syndrome due to paraplegia and vertebral osteoporotic fractures. While PVP is commonly used for the treatment of osteoporotic thoracolumbar vertebral compression fractures, its role in vertebral stabilization in patient with immobilization syndrome has not been reported in the literature. A 73-year-old woman affected by immobilization syndrome due to paraplegia and vertebral osteoporotic fractures was treated with PVP of vertebrae D12, L1, and L4. After PVP, the patient did not need any antalgic therapy, and there was a significant improvement regarding mobilization, performance of physiological functions, daily management of personal care, and treatment of decubitus ulcers, increasing life quality and psychological well-being

DNA methylation ageing clocks and pancreatic cancer risk: pooled analysis of three prospective nested case-control studies

DNA methylation (DNAm) age may reflect age-related variations in biological changes and abnormalities related to ageing. DNAm age acceleration measures have been associated with a number of cancers, but to our knowledge, have not been examined in relation to pancreatic cancer risk or survival. DNAm levels in leukocytes of prediagnostic blood samples of 393 pancreatic cancer cases and 431 matched controls, pooled from three large prospective cohort studies, were used to estimate DNAm age, epigenetic age acceleration (AA), and intrinsic epigenetic age acceleration (IEAA) metrics. Logistic regression and Cox proportional hazard regression models were used to examine the relationship between the various AA and IEAA metrics and pancreatic cancer risk and survival, respectively. The results showed that pancreatic cancer risk was significantly increased across all IEAA metrics, ranging from 83% to 95% increased risk when comparing the third and highest quartiles to the lowest quartile of IEAA. Consistent with these findings, the results from multivariate spline regression analyses showed non-linear relationships between all three IEAA metrics and pancreatic cancer risk with apparent threshold effect including two turning points at minimal and at maximal risks, respectively. There is no evidence of a significant association between pancreatic cancer survival and any of the epigenetic AA or IEAA metrics. Our results indicate DNAm age acceleration, measured in blood prior to cancer diagnosis, is associated with an increased risk of pancreatic cancer in a complex nonlinear, dose–response manner. Epigenetic IEAA metrics may be a useful addition to current methods for pancreatic cancer risk prediction

Remission of Pseudotumor Cerebri Syndrome after Initiating Pregnancy and Menarche: The Puzzling Role of Female Sex Hormones

Pseudotumor cerebri syndrome (PTCS) is characterized by increased intracranial pressure with normal cerebrospinal fluid components and no detectable anomalies of the brain parenchyma on magnetic resonance imaging. Presenting signs and symptoms are heterogeneous, but they commonly include headache, visual disturbances (i.e., vision loss and/or double vision), and papilledema. The etiology is uncertain, but several underlying risk factors associated with PTCS have been identified, including obesity, endocrine abnormalities (e.g., hyperaldosteronism, Cushing syndrome, hyperandrogenism, and Addison disease), medications (e.g., tetracycline, recombinant growth hormone therapy), and viral infections (e.g., chickenpox). Patients with postpubertal PTCS are more typically females in their reproductive age, thereby making crucial (although not fully understood) the role of female hormones in the pathophysiology of this condition. We describe two female patients with PTCS who were followed up at our institution. They experienced prompt (and full) remission of headache and visual disturbances during the first trimester of pregnancy and within the first 2 months after the onset of menarche (i.e., at 20 and 11 years of age), respectively. We reviewed the literature searching for similar cases and hypothesized on the pathophysiologic (and still unclear) involvement of female sex hormones in regulating intracranial pressure, making some patients prone to PTCS

Variation in DNA methylation of human blood over a 1-year period using the Illumina MethylationEPIC array

Assessing DNA methylation profiles in human blood has become a major focus of epidemiologic inquiry. Understanding variability in CpG-specific DNA methylation over moderate periods of time is a critical first step in identifying CpG sites that are candidates for DNA methylation-based etiologic, diagnostic and prognostic predictors of pathogenesis. Using the Illumina MethylationEPIC [850K] BeadArray, DNA methylation was profiled in paired whole blood samples collected approximately 1 year apart from 35 healthy women enrolled in the Nurses Study II cohort. The median intraclass correlation coefficient (ICC) across all CpG loci was 0.19 [Interquartile Range (IQR) 0.00–0.50]; 74.8% of ICCs were in the low range (0–0.5), 16.9% in the mid-range of ICCs (0.5–0.8), and 8.3% in the high-range of ICCs (0.8–1). ICCs were similar for CpG probes on the 450K Illumina array (median 0.17) and the new probes added to the 850K array (median 0.21). ICCs for CpG loci on the sex chromosomes and known metastable epialleles were high (median 0.71, 0.97, respectively), and ICCs among methylation quantitative trait loci (mQTL) CpGs were significantly higher as compared to non-mQTL CpGs (median 0.73, 0.16, respectively, P < 2 × 10–16). We observed wide variation in DNA methylation stability over a 1-year period. Probes considered non-stable, due to substantial variation over a moderate period of time and with minimal variability across individuals could be removed in large epidemiological studies. Moreover, adjusting for technical variation that arises from using high-dimensional arrays is critical