Menopausal Status Modifies Breast Cancer Risk Associated with the Myeloperoxidase (MPO) G463A Polymorphism in Caucasian Women: A Meta-Analysis

BACKGROUND: Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a more precise estimate of association using the odds ratio (OR), we performed a meta-analysis of 2,975 cases and 3,427 controls from three published articles of Caucasian populations living in the United States. Heterogeneity among studies was tested and sensitivity analysis was applied. The lower transcriptional activity AA genotype of MPO in the pre-menopausal population showed significantly reduced risk (OR 0.56-0.57, p = 0.03) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR 1.14; p = 0.34-0.36). High intake of antioxidants (OR 0.67-0.86, p = 0.04-0.05) and carotenoids (OR 0.68-0.86, p = 0.03-0.05) conferred significant protection in the women. Stratified by menopausal status, this effect was observed in pre-menopausal women especially those whose antioxidant intake was high (OR 0.42-0.69, p = 0.04). In post-menopausal women, effect of low intake elicited susceptibility (OR 1.19-1.67, p = 0.07-0.17) to breast cancer. CONCLUSIONS/SIGNIFICANCE: Based on a homogeneous Caucasian population, the MPO G463A polymorphism places post-menopausal women at risk for breast cancer, where this effect is modified by diet

Eosinophils in glioblastoma biology

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review

Use of blood biomarkers to screen for obstructive sleep apnea

Wesley Elon Fleming,1 Jon-Erik C Holty,2 Richard K Bogan,3 Dennis Hwang,4 Aliya S Ferouz-Colborn,4 Rohit Budhiraja,5 Susan Redline,5 Edith Mensah-Osman,6 Nadir Ishag Osman,6 Qing Li,7 Armaghan Azad,1 Susann Podolak,1 Michael K Samoszuk,8 Amabelle B Cruz,8 Yang Bai,8 Jiuliu Lu,8 John S Riley,8 Paula C Southwick8 1Sleep Center Orange County, Irvine, CA, USA; 2Stanford Medical School, VA Palo Alto Health Care System, Pulmonary, Critical Care and Sleep Medicine Section, Palo Alto, CA, USA; 3SleepMed Inc., Bogan Sleep Consultants, LLC, Columbia, SC, USA; 4Sleep Medicine Department, Southern California Permanente Medical Group, Kaiser Permanente, Fontana Medical Center, Fontana, CA, USA; 5Division of Sleep Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA; 6EENA Comprehensive Neurology and Sleep Center, Boynton Beach, FL, USA; 7South Bend Medical Foundation, New Technology and Test Development, South Bend, IN, USA; 8Clinical Research Department, Beckman Coulter, Inc., Brea, CA, USAPurpose: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value. This validation study was conducted in an independent cohort in order to replicate findings from a prior feasibility study.Patients and methods: This multicenter prospective study consecutively enrolled adult male subjects with clinically suspected OSA. All subjects underwent overnight sleep studies. An asymptomatic control group was also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c), C-reactive protein (CRP), uric acid, erythropoietin (EPO), and interleukin-6 (IL-6).Results: The study enrolled 264 subjects. The combination of HbA1c+CRP+EPO (area under the curve 0.78) was superior to the Epworth Sleepiness Scale (ESS; 0.53) and STOP-Bang (0.70) questionnaires. In non-obese subjects, the combination of biomarkers (0.75) was superior to body mass index (BMI; 0.61). Sensitivity and specificity results, respectively, were: HbA1c+CRP+EPO (81% and 60%), ESS (78% and 19%), STOP-Bang (75% and 52%), BMI (81% and 56%), and BMI in non-obese patients (81% and 38%).Conclusion: We verify our hypothesis and replicate our prior feasibility findings that OSA is associated with a characteristic signature cluster of biomarker changes in men. Concurrent elevations of HbA1c, CRP, and EPO levels should generate a high suspicion of OSA and may have utility as an OSA screening tool. Biomarker combinations correlate with OSA severity and, therefore, may assist sleep centers in identifying and triaging higher risk patients for sleep study diagnosis and treatment.Keywords: obstructive sleep apnea, OSA, screening, diagnosis, biomarkers, CRP, HbA1c, erythropoietin, EPO, uric acid, IL-6&nbsp

Peripheral neuropathy in hypereosinophilic syndrome with vasculitis

A 53-year-old woman with non-productive cough of unexplained aetiology for two years, developed a sub-acute symmetrical polyneuropathy involving all four limbs, accompanied by fever, cutaneous rash and myalgia in lower limbs. Laboratory studies revealed a leukocytosis with 70% eosinophils and excluded any cause for the hypereosinophilia. An echocardiogram showed increase in thickness of the atrial septum. Motor and sensory conduction velocity were reduced in ulnar and median nerve, and unrecordable in peroneal and tibial nerves. A sural nerve biopsy showed an axonal degeneration involving myelinated and unmyelinated fibers as well as a vasculitis with fibrinoid necrosis and perivascular infiltration of eosinophils. There was considerable clinical and laboratorial improvement with the use of steroids. The differential diagnosis between idiopathic hypereosinophilic syndrome and other disorders known to course with vasculitis and hypereosinophilia is discussed