70 research outputs found

    Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention.

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    Environmental and lifestyle factors are believed to account for >80% of breast cancers; however, it is not well understood how and when these factors affect risk and which exposed individuals will actually develop the disease. While alcohol consumption, obesity, and hormone therapy are some known risk factors for breast cancer, other exposures associated with breast cancer risk have not yet been identified or well characterized. In this paper, it is proposed that the identification of blood epigenetic markers for personal, in utero, and ancestral environmental exposures can help researchers better understand known and potential relationships between exposures and breast cancer risk and may enable personalized prevention strategies

    Recognition and Treatment of Cognitive Dysfunction in Major Depressive Disorder

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    Major Depressive Disorder (MDD) is a prevalent, chronic, disabling, and multidimensional mental disorder. Cognitive dysfunction represents a core diagnostic and symptomatic criterion of MDD, and is a principal determinant of functional non-recovery. Cognitive impairment has been observed to persist despite remission of mood symptoms, suggesting dissociability of mood and cognitive symptoms in MDD. Recurrent impairments in several domains including, but not limited to, executive function, learning and memory, processing speed, and attention and concentration, are associated with poor psychosocial and occupational outcomes. Attempts to restore premorbid functioning in individuals with MDD requires regular screenings and assessment of objective and subjective measures of cognition by clinicians. Easily accessible and cost-effective tools such as the THINC-integrated tool (THINC-it) are suitable for use in a busy clinical environment and appear to be promising for routine usage in clinical settings. However, antidepressant treatments targeting specific cognitive domains in MDD have been insufficiently studied. While select antidepressants, e.g., vortioxetine, have been demonstrated to have direct and independent pro-cognitive effects in adults with MDD, research on additional agents remains nascent. A comprehensive clinical approach to cognitive impairments in MDD is required. The current narrative review aims to delineate the importance and relevance of cognitive dysfunction as a symptomatic target for prevention and treatment in the phenomenology of MDD

    Promoter DNA Methylation of Oncostatin M receptor-β as a Novel Diagnostic and Therapeutic Marker in Colon Cancer

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    In addition to genetic changes, the occurrence of epigenetic alterations is associated with accumulation of both genetic and epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidate genes that comprise part of the emerging “cancer methylome”. In the present study, we first tested 23 candidate genes for promoter methylation in a small number of primary colon tumor tissues and controls. Based on these results, we then examined the methylation frequency of Oncostatin M receptor-β (OSMR) in a larger number of tissue and stool DNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary colon cancer tissues (80%, 80/100), but not in normal tissues (4%, 4/100). Methylation of OSMR was also detected in stool DNA from colorectal cancer patients (38%, 26/69) (cut-off in TaqMan-MSP, 4). Detection of other methylated markers in stool DNA improved sensitivity with little effect on specificity. Promoter methylation mediated silencing of OSMR in cell lines, and CRC cells with low OSMR expression were resistant to growth inhibition by Oncostatin M. Our data provide a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target in this disease. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC

    BMI and breast cancer risk around age at menopause

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    BACKGROUND: A high body mass index (BMI, kg/m 2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55

    The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

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