Specific fatty acid intake and the risk of pancreatic cancer in Canada

The possible association of specific fatty acid (FA) intake and pancreatic cancer risk was investigated in a population-based case–control study of 462 histologically confirmed cases and 4721 frequency-matched controls in eight Canadian provinces between 1994 and 1997. Dietary intake was assessed by means of a self-administered food frequency questionnaire. Unconditional logistic regression was used to assess associations between dietary FAs and pancreatic cancer risk. After adjustment for age, province, body mass index, smoking, educational attainment, fat and total energy intake, statistically significant inverse associations were observed between pancreatic cancer risk and palmitate (odds ratios (ORs)=0.73; 95% confidence intervals (CIs) 0.56–0.96; P-trend=0.02), stearate (OR=0.70; 95% CI 0.51–0.94; P-trend=0.04), oleate (OR=0.75; 95% CI 0.55–1.02; P-trend=0.04), saturated FAs (OR=0.67; 95% CI 0.50–0.91; P-trend=0.01), and monounsaturated FAs (OR=0.72; 95% CI 0.53–0.98; P-trend=0.02), when comparing the highest quartile of intake to the lowest. Significant interactions were detected between body mass index and both saturated and monounsaturated FAs, with a markedly reduced risk associated with intake of stearate (OR=0.36; 95% CI 0.18–0.70; P-trend=0.001), oleate (OR=0.36; 95% CI 0.19–0.72; P-trend=0.002), saturated FAs (OR=0.35; 95% CI 0.18–0.67; P-trend=0.002), and monounsaturated FAs (OR=0.32; 95% CI 0.16–0.63; P-trend<0.0001) among subjects who are obese. The results suggest that substituting polyunsaturated FAs with saturated or monounsaturated FAs may reduce pancreatic cancer risk, independently of total energy intake, particularly among obese subjects

The bed nucleus of stria terminalis and the amygdala as targets of antenatal glucocorticoids: implications for fear and anxiety responses

Rationale: Several human and experimental studies have shown that early life adverse events can shape physical and mental health in adulthood. Stress or elevated levels of glucocorticoids (GCs) during critical periods of development seem to contribute for the appearance of neurospyschiatric conditions such as anxiety and depression, albeit the underlying mechanisms remain to be fully elucidated. Objectives: The aim of the present study was to determine the long-term effect of prenatal erxposure to dexamethasone- DEX (synthetic GC widely used in clinics) in fear and anxious behavior and identify the neurochemical, morphological and molecular correlates. Results: Prenatal exposure to DEX triggers a hyperanxious phenotype and altered fear behavior in adulthood. These behavioral traits were correlated with increased volume of the bed nucleus of the stria terminalis (BNST), particularly the anteromedial subivision which presented increased dendritic length; in parallel, we found an increased expression of synapsin and NCAM in the BNST of these animals. Remarkably, DEX effects were opposite in the amygdala, as this region presented reduced volume due to significant dendritic atrophy. Albeit no differences were found in dopamine and its metabolite levels in the BNST, this neurotransmitter was substantially reduced in the amygdala, which also presented an up-regulation of dopamine receptor 2. Conclusions: Altogether our results show that in utero DEX exposure can modulate anxiety and fear behavior in parallel with significant morphological, neurochemical and molecular changes; importantly, GCs seem to differentially affect distinct brain regions involved in this type of behaviors.This study was supported by a grant from the Institute for the Study of Affective Neuroscience (ISAN). AJR is supported by a Fundação para a Ciência e Tecnologia (FCT) grant

A genetic analysis of nitric oxide-mediated signaling during chronological aging in the yeast

In mammals, NO•, a signaling molecule is implicated in the regulation of vasodilation, neurotransmission and immune response. It is believed that NO• is a signaling molecule also in unicellular organism like yeast and may be involved in the regulation of apoptosis and sporulation. It has been reported that NO• is produced during chronological aging (CA) leading to an increase of the superoxide level, which in turn mediates apoptosis. Since this conclusion was based on indirect measurements of NO• by the Griess reaction, the role of NO• signaling during CA in the yeast remains uncertain. We investigated this issue more precisely using different genetic and biochemical methodologies. We used cells lacking the factors influencing nitrosative stress response like flavohemoglobin metabolizing NO•, S-nitrosoglutathione reductase metabolizing S-nitrosoglutathione and the transcription factor Fzf1p mediating NO• response. We measured the standard parameters describing CA and found an elevation in the superoxide level, percentage of death cells, the level of TUNEL positive cells and a decrease in proliferating potential. These observations showed no significant differences between wild type cells and the disruptants except for a small elevation of the superoxide level in the Δsfa1 mutant. The intracellular NO• level and flavohemoglobin expression decreased rather than increased during CA. Products of general nitrogen metabolism and protein tyrosine nitration were slightly decreased during CA, the magnitude of changes showing no differences between the wild type and the mutant yeast. Altogether, our data indicate that apoptosis during yeast CA is mediated by superoxide signaling rather than NO• signaling

Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk

The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk

A 50% higher prevalence of life-shortening chronic conditions among cancer patients with low socioeconomic status

Background: Comorbidity and socioeconomic status (SES) may be related among cancer patients. Method : Population-based cancer registry study among 72 153 patients diagnosed during 1997-2006. Results : Low SES patients had 50% higher risk of serious comorbidity than those with high SES. Prevalence was increased for each cancer site. Low SES cancer patients had significantly higher risk of also having cardiovascular disease, chronic obstructive pulmonary diseases, diabetes mellitus, cerebrovascular disease, tuberculosis, dementia, and gastrointestinal disease. One-year survival was significantly worse in lowest vs highest SES, partly explained by comorbidity. Conclusion : This illustrates the enormous heterogeneity of cancer patients and stresses the need for optimal treatment of cancer patients with a variety of concomitant chronic conditions

Antioxidant intake among Brazilian adults - The Brazilian Osteoporosis Study (BRAZOS): a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Antioxidant nutrient intake and the lesser formation of free radicals seem to contribute to chronic diseases. The aim of the present study was to evaluate the intake profile of the main dietary antioxidants in a representative sample of the adult Brazilian population and discuss the main consequences of a low intake of these micronutrients on overall health.</p> <p>Methods</p> <p>The sample comprised 2344 individuals aged 40 years or older from 150 cities and was based on a probabilistic sample from official data. The research was conducted through in-home interviews administered by a team trained for this purpose. Dietary intake information was obtained through 24-h recall. The Nutrition Data System for Research software program was used to analyze data on the intake of vitamins A, C and E, selenium and zinc, which was compared to Dietary Reference Intakes (DRIs). Differences in intake according to sex, anthropometrics, socioeconomic status and region were also evaluated. The SPSS statistical package (version 13) was used for the statistical analysis. P-values < 0.05 were considered significant.</p> <p>Results</p> <p>Higher proportions of low intake in relation to recommended values were found for vitamin E (99.7%), vitamin A (92.4%) and vitamin C (85.1%) in both genders. Intake variations were found between different regions, which may reflect cultural habits.</p> <p>Conclusion</p> <p>These results should lead to the development of public health policies that encourage educational strategies for improving the intake of micronutrients, which are essential to overall health and prevention of non-communicable diseases.</p

Pancreatitis and pancreatic cancer in two large pooled case–control studies

The association between duration of pancreatitis and pancreatic cancer has not been well characterized in large population-based studies. We conducted detailed analyses to determine the association between pancreatitis onset and pancreatic cancer risk. Data from two case–control studies of pancreatic cancer (n = 4515) in the San Francisco Bay Area and the M.D. Anderson Cancer Center were pooled for analysis (1,663 cases, 2,852 frequency-matched controls). Adjusted odds ratios (OR) were estimated using a random-effects model. In the pooled multivariable model, history of pancreatitis was associated with a 7.2-fold increased risk estimate for pancreatic cancer [95% confidence interval (CI): 4.0, 13]. The risk estimate was nearly 10-fold in participants aged &lt;55 years (OR = 9.9, 95% CI: 3.5, 28). A shorter temporal history of pancreatitis was more closely associated with pancreatic cancer than was a longer temporal history: &lt;3 years (OR = 29, 95% CI: 12, 71), 3–10 years (OR = 2.6, 95% CI: 1.5, 5.6), and &gt;10 years (OR = 1.8, 95% CI: 0.7, 4.5, p trend &lt; 0.001). A short temporal history of pancreatitis was highly associated with pancreatic cancer, suggesting that pancreatitis may be an early manifestation of pancreatic cancer in some individuals. Pancreatic cancer should be considered in the differential diagnosis of individuals with an episode of pancreatitis

HIV prevalence among female sex workers, drug users and men who have sex with men in Brazil: A Systematic Review and Meta-analysis

<p>Abstract</p> <p>Background</p> <p>The Brazilian response towards AIDS epidemic is well known, but the absence of a systematic review of vulnerable populations ─ men who have sex with men (MSM), female sex workers (FSW), and drug users (DU) remains a main gap in the available literature. Our goal was to conduct a systematic review and meta-analysis of studies assessing HIV prevalence among MSM, FSW and DU, calculating a combined pooled prevalence and summarizing factors associated the pooled prevalence for each group.</p> <p>Methods</p> <p>Nine electronic databases (MEDLINE via PubMed, EMBASE, Cochrane CENTRAL, AIDSLINE, AMED, CINAHL, TOXNET, SciELO, and ISI-Web of Science) were searched for peer-reviewed papers published in English, French, Spanish or Portuguese, from 1999 to 2009. To be included in the review, studies had to measure HIV prevalence and/or incidence as the primary outcome among at least one specific population under analysis.</p> <p>Results</p> <p>The studies targeting the three populations analyzed mostly young participants aged 30 years or less. Among FSW, eight studies were selected (3,625 participants), consistently identifying higher condom use with sexual clients than with occasional and stable partners. The combined HIV prevalence for FSW was 6.2 (95% CI: 4.4-8.3). Ten studies targeting MSM were identified (6,475 participants). Unprotected anal intercourse was commonly reported on those studies, but with great variability according to the nature of the relationship - stable vs. occasional sex partners - and sexual practice - receptive vs. insertive anal sex. Pooled HIV prevalence for MSM was 13.6 (95% CI: 8.2-20.2). Twenty nine studies targeting DU were identified (13,063 participants). Those studies consistently identified injection drug use and syringe/needle sharing as key predictors of HIV-infection, as well as engagement in sex work and male-to-male sex. The combined HIV prevalence across studies targeting DU was 23.1 (95% CI: 16.7-30.2).</p> <p>Conclusions</p> <p>FSW, MSM and DU from Brazil have a much risk of acquiring HIV infection compared to the general population, among which HIV prevalence has been relatively low (~0.6%). Those vulnerable populations should be targeted by focused prevention strategies that provide accurate information, counseling and testing, as well as concrete means to foster behavior change (e.g. access to condoms, drug abuse treatment, and clean syringes in the case of active injecting drug users), tailored to gender and culture-specific needs. Programs that provide these services need to be implemented on public health services throughout the country, in order to decrease the vulnerability of those populations to HIV infection.</p