Flavonoid intake and breast cancer incidence and survival

Flavonoids are phytochemicals found in a variety of foods that have demonstrated anti-carcinogenic properties in experimental studies. Two epidemiologic studies conducted in the Mediterranean have observed an inverse association between dietary intake of certain flavonoid classes and breast cancer incidence. However, it is unknown whether a similar association is evident among American women. Further, whether flavonoids affect breast cancer survival is unknown. We investigated whether dietary flavonoid intake influences breast cancer incidence and survival among a population-based cohort of American women. Methods: A population-based, case-control study was conducted among women ages 20-98 years who resided in Nassau and Suffolk counties in Long Island, New York. Cases were newly diagnosed with a first invasive breast cancer between August 1, 1996 and July 31, 1997; controls were identified using random digit dialing and Health Care Finance Administration rosters. Trained interviewers administered an in-person questionnaire to participants on known and suspected breast cancer risk factors. Participants also completed a self-administered food frequency questionnaire regarding their average frequency of food and beverage consumption in the prior 12 months. For those with known menopausal status, 1,434 breast cancer cases and 1,440 controls provided adequate dietary responses. Case medical records were obtained to assess tumor characteristics and initial course of treatment. Cases were followed-up through 2002. All-cause mortality (n = 173) and breast cancer-specific mortality (n = 113) were determined through the National Death Index. Results: Increasing intake of flavonols, flavones, flavan-3-ols, and lignans, as reported at the case-control interview, was associated with a reduced risk of incident postmenopausal breast cancer among Long Island women. All-cause mortality among postmenopausal women was reduced for intake of flavones and isoflavones and similar results were observed for breast cancer-specific mortality. Conclusion: Findings provide evidence for a beneficial effect of flavones, flavonols and lignans on breast cancer incidence among post-menopausal women. Results from the follow-up study indicate that mortality among post-menopausal breast cancer patients is reduced in association with high intake of flavones and isoflavones near the time of diagnosis. These findings suggest American women can consume sufficient levels of flavonoid-rich foods to benefit from their potential chemopreventive effects

Analysis of the Relationship Between Diet and Exercise Beliefs and Actual Behaviors Among Breast Cancer Survivors in Northwest Ohio

Introduction: Studies have shown that a diet high in fruit and vegetable intake, as well as a routine including daily exercise or physical activity, can independently affect relapse rates and survivorship in breast cancer patients. Fruits and vegetables contain powerful anti-oxidant molecules, capable of preventing tumor formation and proliferation. Exercise can lower circulating levels of estrogen, the female hormone responsible for tumor proliferation in the estrogen-sensitive form of the disease. The most beneficial results have been shown in women who exercise and consume a diet rich in fruits and vegetables. We studied the attitudes towards and behaviors related to fruit and vegetable intake and exercise in a cohort of breast cancer survivors in northwest Ohio. Materials and Methods: Data were gathered from a survey sent out by the Northwest Ohio Branch of the Susan G. Komen For the Cure Foundation. We assessed and evaluated survivors’ self-reported beliefs, attitudes, and behaviors regarding exercise and fruit and vegetable intake. Results: Nearly half of the survivors (46.5%) reported being unsure or in disagreement with the statement “Eating at least 5 servings of fruits and/or vegetables per day will reduce the risk of breast cancer recurrence.” Only 46.8% of those in agreement with the previous statement actually report eating at least 5 fruits and/or vegetables per day. With respect to exercise, 32.9% reported being unsure or in disagreement with the statement “Engaging in regular physical activity will reduce the risk of breast cancer recurrence.” Only 68.5% of those in agreement with the previous statement report any physical activity in the past 30 days. Conclusions: Many breast cancer survivors do not appear to be aware of the benefits of diet and exercise. Further, a large proportion of those who are aware of the benefits do not adapt a healthy diet and exercise as part of their lifestyle. A majority of these survivors see a primary care physician, which we believe is the best venue to bridge this education gap. It is apparent by the pattern our data shows that more needs to be done to educate breast cancer survivors about the benefits of exercise and fruit and vegetable intake. Steps need to be taken to ensure that those who are educated also remain motivated to engage in a healthy lifestyle with the hopes of avoiding breast cancer recurrence

Early Stage Breast Cancer and Its Association with Diet and Exercise-Related Perceptions and Behaviors to Prevent Recurrence

Background The favorable prognosis for early stage breast cancer survivors may be a reason for the minimal research regarding their quality of life. Prior research has observed more long-term weight gain among early stage survivors compared to cancer-free women of a similar age. It would be useful to study survivors’ perceptions and reported behaviors regarding diet and exercise to see if there is a correlation with previous studies. Methods A sample of 700 breast cancer survivors from Ohio and Michigan was randomly selected from the Northwest Ohio affiliate of the Susan G. Komen For the Cure mailing list and sent a survey for completion. Results 389 survivors completed the survey and among Stage 1 (50/197 = 25.4%) and Stage 2 survivors (24/105 = 22.9%), a small proportion had a positive correlation between self-reported dietary behaviors and their perceived benefits of eating fruits and vegetables. Similar correlations were observed between their self-reported exercise behaviors and their perceived benefits of exercise (Stage 1: 36/197 = 18.3%, Stage 2: 18/105 = 17.1%). Conclusions Regardless of stage, a small proportion of survivors’ self-reported dietary and exercise behaviors match their perceived benefits of diet and exercise. Factors such as access, motivation, and lack of co-morbidities among early stage survivors may prevent them from living healthier post-diagnosis. More thorough dietary and clinical measurements will provide greater certainty. Thus, innovative, sustainable programs must be accessible and provide motivation and social support from family, friends, and other survivors to truly improve quality of life

Nutrient Pathways and Breast Cancer Risk: The Long Island Breast Cancer Study Project

The relative importance of biochemical pathways has not been previously examined when considering the influence of diet on breast cancer risk. To address this issue, we utilized interview data from a population-based sample of 1,463 breast cancer cases and 1,500 controls. Dietary intake was assessed shortly after diagnosis using a 101-item food frequency questionnaire. Age- and energy-adjusted odds ratios (ORs) for individual micro- and macronutrients were estimated with logistic regression. Hierarchical modeling was employed to account for biologically plausible nutrient pathways (one-carbon metabolism, oxidative stress, glycemic control and phytoestrogens). Effect estimates from hierarchical modeling were more precise and plausible compared to those from multivariable models. The strongest relationship observed was for the glycemic control pathway, but confidence intervals (CI) were wide [OR (95% CI): 0.86 (0.62, 1.21)]. Little or no effect was observed for the one-carbon metabolism, oxidative stress and phytoestrogen pathways. Associations were similar when stratified by supplement use. Our approach that emphasizes biochemical pathways, rather than individual nutrients, revealed that breast cancer risk may be more strongly associated with glycemic control factors than those from other pathways considered. Our study emphasizes the importance of accounting for multiple nutrient pathways when examining associations between dietary intake and breast cancer

Genetic variation in multiple biologic pathways, flavonoid intake, and breast cancer

We previously reported an inverse association between flavonoid intake and breast cancer incidence, which has been confirmed by others; but no studies have considered simultaneously potential interactions of flavonoids with multiple genetic polymorphisms involved in biologically-relevant pathways (oxidative stress, carcinogen metabolism, DNA repair, and one-carbon metabolism)

GUCY2C Opposes Systemic Genotoxic Tumorigenesis by Regulating AKT-Dependent Intestinal Barrier Integrity

The barrier separating mucosal and systemic compartments comprises epithelial cells, annealed by tight junctions, limiting permeability. GUCY2C recently emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt-villus homeostasis. Here, the contribution of GUCY2C to barrier integrity opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C (Gucy2c−/−) exhibited barrier hyperpermeability associated with reduced junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier permeability associated with increased junctional proteins. Further, silencing GUCY2C exacerbated, while activation reduced, chemical barrier disruption and colitis. Moreover, eliminating GUCY2C amplified, while activation reduced, systemic oxidative DNA damage. This genotoxicity was associated with increased spontaneous and carcinogen-induced systemic tumorigenesis in Gucy2c−/− mice. GUCY2C regulated barrier integrity by repressing AKT1, associated with increased junction proteins occludin and claudin 4 in mice and Caco2 cells in vitro. Thus, GUCY2C defends the intestinal barrier, opposing colitis and systemic genotoxicity and tumorigenesis. The therapeutic potential of this observation is underscored by the emerging clinical development of oral GUCY2C ligands, which can be used for chemoprophylaxis in inflammatory bowel disease and cancer

Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3′-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP

A 'snip' in time: what is the best age to circumcise?

<p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p

Mechanisms of Hybrid Oligomer Formation in the Pathogenesis of Combined Alzheimer's and Parkinson's Diseases

Background: Misfolding and pathological aggregation of neuronal proteins has been proposed to play a critical role in the pathogenesis of neurodegenerative disorders. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are frequent neurodegenerative diseases of the aging population. While progressive accumulation of amyloid b protein (Ab) oligomers has been identified as one of the central toxic events in AD, accumulation of a-synuclein (a-syn) resulting in the formation of oligomers and protofibrils has been linked to PD and Lewy body Disease (LBD). We have recently shown that Ab promotes a-syn aggregation and toxic conversion in vivo, suggesting that abnormal interactions between misfolded proteins might contribute to disease pathogenesis. However the molecular characteristics and consequences of these interactions are not completely clear. Methodology/Principal Findings: In order to understand the molecular mechanisms involved in potential Ab/a-syn interactions, immunoblot, molecular modeling, and in vitro studies with a-syn and Ab were performed. We showed in vivo in the brains of patients with AD/PD and in transgenic mice, Ab and a-synuclein co-immunoprecipitate and form complexes. Molecular modeling and simulations showed that Ab binds a-syn monomers, homodimers, and trimers, forming hybrid ringlike pentamers. Interactions occurred between the N-terminus of Ab and the N-terminus and C-terminus of a-syn. Interacting a-syn and Ab dimers that dock on the membrane incorporated additional a-syn molecules, leading to th

Narcissism and the strategic pursuit of short-term mating : universal links across 11 world regions of the International Sexuality Description Project-2.

Previous studies have documented links between sub-clinical narcissism and the active pursuit of short-term mating strategies (e.g., unrestricted sociosexuality, marital infidelity, mate poaching). Nearly all of these investigations have relied solely on samples from Western cultures. In the current study, responses from a cross-cultural survey of 30,470 people across 53 nations spanning 11 world regions (North America, Central/South America, Northern Europe, Western Europe, Eastern Europe, Southern Europe, Middle East, Africa, Oceania, Southeast Asia, and East Asia) were used to evaluate whether narcissism (as measured by the Narcissistic Personality Inventory; NPI) was universally associated with short-term mating. Results revealed narcissism scores (including two broad factors and seven traditional facets as measured by the NPI) were functionally equivalent across cultures, reliably associating with key sexual outcomes (e.g., more active pursuit of short-term mating, intimate partner violence, and sexual aggression) and sex-related personality traits (e.g., higher extraversion and openness to experience). Whereas some features of personality (e.g., subjective well-being) were universally associated with socially adaptive facets of Narcissism (e.g., self-sufficiency), most indicators of short-term mating (e.g., unrestricted sociosexuality and marital infidelity) were universally associated with the socially maladaptive facets of narcissism (e.g., exploitativeness). Discussion addresses limitations of these cross-culturally universal findings and presents suggestions for future research into revealing the precise psychological features of narcissism that facilitate the strategic pursuit of short-term mating