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Reduced Risk (reduced + risk)
Selected AbstractsCommon CX3CR1 Alleles Are Associated With a Reduced Risk of HeadachesHEADACHE, Issue 7 2008Christophe Combadière PhD Objectives., The aim of this study was to investigate the role of the chemokine receptor CX3CR1 in headaches and migraine. Methods., Distribution of 2 polymorphisms of the chemokine receptor CX3CR1 (V249I and T280M) was determined in a population-based sample of 1179 elderly individuals. Results., Heterozygotes for both CX3CR1 polymorphisms had a reduced risk of recurrent headaches, with an odds ratio (OR) of 0.64 (95% confidence interval [CI] = 0.46-0.90) for the I249 allele and 0.55 (95% CI = 0.38-0.81) for the M280 allele. Haplotype analysis showed that carriers of the rarer CX3CR1 I249-M280 haplotype had a reduced risk of recurrent headaches, with an OR of 0.57 (95% CI = 0.41-0.80, P = .001). This association was seen for both nonmigraine headaches (OR = 0.47, 95% CI = 0.28-0.79, P = .004) and migraine (OR = 0.65, 95% CI = 0.43-0.98, P = .041). Conclusions., These results need to be replicated but suggest that the chemokine receptor CX3CR1 may play a role in recurrent headaches. [source] Maternal antecedents for cerebral palsy in extremely preterm babies: a case-control studyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2001Peter H Gray MD FRCPI FRACP FRCPCH The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks'gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids. [source] Long-acting insulin analogues vs.DIABETES OBESITY & METABOLISM, Issue 4 2009NPH human insulin in type 1 diabetes. Aim:, Basal insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human insulin or long-acting insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human insulin and each long-acting analogue. Methods:, Of 285 randomized controlled trials with a duration > 12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov, 20 met eligibility criteria (enrolling 3693 and 2485 in the long-acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed. Results:, Long-acting analogues had a small, but significant effect on HbA1c [-0.07 (,0.13; ,0.01)%; p = 0.026], in comparison with NPH human insulin. When analysing the effect of long-acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human insulin [by 0.26 (0.06;0.47) kg/m2; p = 0.012]. Long-acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01]. Conclusions:, The switch from NPH to long-acting analogues as basal insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia. [source] Effects of insulin resistance on endothelial function: possible mechanisms and clinical implicationsDIABETES OBESITY & METABOLISM, Issue 10 2008D Tousoulis Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin,angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials. [source] Genetic variation and decreased risk for obesity in the Atherosclerosis Risk in Communities StudyDIABETES OBESITY & METABOLISM, Issue 4 2007M. L. Hart Sailors Aim:, To investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13,405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. Methods:, We tested the association between the single-locus and multilocus genotypes and obesity-related measures [body mass index (BMI), body weight (BW), waist,hip ratio, waist circumference and leptin levels], adjusted for age, physical activity level, smoking status, diabetic status, prevalence of coronary heart disease, hypertension, stroke or transient ischaemic attack. Results:, AA and white female carriers of the MC4R I103 allele exhibited significantly lower BW than non-carriers of this allele (p < 0.05 and p < 0.01 respectively). AA female carriers of both the LEP A19 allele and the MC4R I103 allele were 63% [odds ratio (OR) = 0.37, 95% confidence interval (CI) (0.18,0.78)] less likely to be obese, and white female carriers of the same two alleles were 46% [OR = 0.54, 95% CI (0.32,0.91)] less likely to be obese, than non-carriers of the variant alleles. Female carriers of both the LEP A19 and MC4R I103 alleles had significantly lower BW (p < 0.05), BMI (p < 0.05) and plasma leptin (p < 0.01) than the non-carriers of both the alleles. Carriers of the two variant alleles had lower BMI over the 9-year course of the ARIC study and significantly lower weight gain from age 25 years. No significant joint effect of these two variants was observed in males. Conclusion:, These results suggest that variation within the LEP and MC4R genes is associated with reduced risk for obesity in females. [source] Metabolic, endocrine and haemodynamic risk factors in the patient with peripheral arterial diseaseDIABETES OBESITY & METABOLISM, Issue 2002Jill J. F. Belch The morbidity and mortality associated with peripheral arterial disease (PAD) creates a huge burden in terms of costs both to the patient and to the health service. PAD is a deleterious and progressive condition that causes a marked increase in the risk of cardiovascular and cerebrovascular events. Further, PAD has a major negative impact on quality of life and mortality, and is associated with an increased risk of limb amputation. The clinical profile of patients at risk of PAD overlaps considerably with the known cardiovascular risk factors. These include, increasing age, smoking habit, diabetes, hypertension, dyslipidaemia, male sex and hyperhomocysteinaemia. For women, hormone replacement therapy appears to be associated with a reduced risk of PAD. Published PAD guidelines recommend aggressive management of risk factors, stressing the importance of lifestyle modification, antiplatelet agents, treating dyslipidaemia and diabetes. However, a large number of patients with PAD go undetected, either because they do not report their symptoms or because they are asymptomatic. It is therefore important to improve detection rates so that these patients can receive appropriate risk factor management. [source] Diabetes mellitus and alcoholDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2004Albert van de Wiel Abstract Alcohol influences glucose metabolism in several ways in diabetic patients as well as in non-diabetic patients. Since alcohol inhibits both gluconeogenesis and glycogenolysis, its acute intake without food may provoke hypoglycaemia, especially in cases of depleted glycogen stores and in combination with sulphonylurea. Consumed with a meal including carbohydrates, it is the preferred fuel, which may initially lead to somewhat higher blood glucose levels and hence an insulin response in type 2 diabetic patients. Depending on the nature of the carbohydrates in the meal, this may be followed by reactive hypoglycaemia. Moderate consumption of alcohol is associated with a reduced risk of atherosclerotic disorders. Diabetic patients benefit from this favourable effect as much as non-diabetic patients. Apart from effects on lipid metabolism, haemostatic balance and blood pressure, alcohol improves insulin sensitivity. This improvement of insulin sensitivity may also be responsible for the lower incidence of type 2 diabetes mellitus reported to be associated with light-to-moderate drinking. In case of moderate and sensible use, risks of disturbances in glycaemic control, weight and blood pressure are limited. Excessive intake of alcohol, however, may not only cause loss of metabolic control, but also annihilate the favourable effects on the cardiovascular system. Copyright © 2004 John Wiley & Sons, Ltd. [source] Indiscriminate nursing in communal breeders: a role for genomic imprintingECOLOGY LETTERS, Issue 3 2003Alexandre Roulin Abstract In several communally nesting mammal species, females indiscriminately nurse each others' offspring. Previous hypotheses have suggested that the inability to recognize one's own young during lactation is the result of costs incurred from recognition errors. Here, we propose an alternative hypothesis based on sexual conflict theory and genomic imprinting. In polygynous species, males copulate with several females that may later breed communally. Under such conditions, males benefit from indiscriminate nursing of all their offspring and the reduced risk of female infanticide. This may have selected for paternally expressed genes that suppress kin recognition during lactation. [source] The natural history of quitting smoking: findings from the International Tobacco Control (ITC) Four Country SurveyADDICTION, Issue 12 2009Natalie Herd ABSTRACT Aims To describe the long-term natural history of a range of potential determinants of relapse from quitting smoking. Design, setting and participants A survey of 2502 ex-smokers of varying lengths of time quit recruited as part of the International Tobacco Control (ITC) Four Country Survey (Australia, Canada, United Kingdom, United States) across five annual waves of surveying. Measurements Quitters were interviewed by telephone at varying durations of abstinence, ranging from 1 to 1472 days (about 4 years) post-quitting. Smoking-related beliefs and experiences (i.e. urges to smoke; outcome expectancies of smoking and quitting; and abstinence self-efficacy) were included in the survey. Findings Most theorized determinants of relapse changed over time in a manner theoretically associated with reduced risk of relapse, except most notably the belief that smoking controls weight, which strengthened. Change in these determinants changed at different rates: from a rapidly asymptoting log function to a less rapidly asymptoting square-root function. Conclusions Variation in patterns of change across time suggests that the relative importance of each factor to maintaining abstinence may similarly vary. [source] Risk factors for epiploic foramen entrapment colic in a UK horse population: A prospective case-control studyEQUINE VETERINARY JOURNAL, Issue 4 2008D. C. ARCHER Summary Reasons for performing study: Epiploic foramen entrapment (EFE) is a common cause of small intestinal strangulation in the horse and its epidemiology requires further investigation. Objectives: To identify horse- and management-level risk factors for EFE and to explore reasons for the apparent seasonality of this condition. Hypothesis: Horses exhibiting certain behaviours and those exposed to particular management practices that vary seasonally are at increased risk of EFE. Methods: A prospective unmatched, multicentre case-control study was conducted over 24 months in the UK. Data on 77 cases and 216 control horses were obtained from 9 collaborating clinics and logistic regression was used to identify associations between horse and management variables and the likelihood of EFE. Results: In a final multivariable model crib-biting/ windsucking behaviour was associated with the largest increase in likelihood of EFE. A history of colic in the previous 12 months, increased stabling in the previous 28 days and height of the horse also increased the likelihood of EFE. Horses with access to a mineral/salt lick, those easily frightened and horses not fed at the same time as others were at reduced risk of EFE. Conclusions: Horses exhibiting certain behaviours, those with a previous history of colic and horses of greater height appear to be at inherently greater risk of EFE. The increase in likelihood of EFE with increased duration of stabling may explain the apparent seasonality of this condition. Potential relevance: These findings assist identification of horses at high-risk of EFE and provide information on management strategies that may reduce this risk. If the observed associations are causal, avoiding sudden increases in duration of stabling, not feeding horses in the same group at the same time and providing a mineral/salt lick may reduce the likelihood of EFE. The risk factors identified in this study provide important clues to the aetiology of EFE. [source] Drinking pattern and risk of non-fatal myocardial infarction: a population-based case,control studyADDICTION, Issue 3 2004Maurizio Trevisan ABSTRACT Aims Alcohol consumption has been associated with a reduced risk of heart disease incidence and mortality. However, most studies have focused on an average volume per specific time period and have paid little attention to the pattern of drinking. The aim of this study was to examine the association between various drinking patterns and myocardial infarction (MI). Design A population-based case,control study. Methods Participants were 427 white males with incident MI and 905 healthy white male controls (age 35,69 years) selected randomly from two Western New York counties. During computer-assisted interviews detailed information was collected regarding patterns of alcohol consumption during the 12,24 months prior to interview (controls) or MI (cases). Findings Compared to life-time abstainers, adjusted odds ratios (ORs) and 95% confidence interval (CI) for non-current and current drinkers were 0.66 (0.31,1.39) and 0.50 (0.24,1.02), respectively. Daily drinkers exhibited a significantly lower OR (0.41) compared to life-time abstainers. Participants who drank mainly without food had an OR of 1.49 (0.96,2.31) compared to those who drank mainly with food and 0.62 (0.28,1.37) compared to life-time abstainers. Men who reported drinking only at weekends had a significantly greater MI risk [1.91; (1.21,3.01)] compared to men who drank less than once/week, but not compared to life-time abstainers [0.91 (0.40,2.07)]. Conclusions Our results indicate that patterns of alcohol use have important cardiovascular health implications. [source] Alcohol inflammation and coronary heart diseaseADDICTION BIOLOGY, Issue 3 2003ARMIN IMHOF This overview summarizes the experimental and epidemiological evidence linking alcohol consumption and the immune system. It focuses on findings supporting the notion that moderate alcohol consumption exerts anti-inflammatory effects which may explain, at least in part, the reduced risk of coronary heart disease morbidity and mortality in these subjects. Alcohol consumption has been shown consistently to be associated with all-cause mortality in a J- or U-shaped manner. This is due primarily to reduced risk of coronary heart disease (CHD) mortality among moderate consumers of alcohol compared to abstainers and heavy drinkers. Several mechanisms have been suggested by which moderate alcohol consumption could lower risk of CHD. However, changes in lipids, such as increased HDL cholesterol and apolipoprotein A1 or a favourable haemostatic profile, can only partly explain the beneficial effects. Recently, anti-inflammatory effects of moderate intake of alcohol have been considered as an additional possible explanation, as inflammation has a fundamental role in the initiation, progression and the thrombotic complications of atherosclerosis. [source] MTHFR 677C>T and ACE D/I Polymorphisms in Migraine: A Systematic Review and Meta-AnalysisHEADACHE, Issue 4 2010Markus Schürks MD (Headache 2010;50:588-599) Background., Data on the association between the MTHFR 677C>T and ACE D/I polymorphisms and migraine including aura status are conflicting. Objective., The objective of this study is to perform a systematic review and meta-analysis on this topic. Methods., We searched for studies published until March 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies and reviews on the topic. Assessment for eligibility of studies and extraction of data was performed by 2 independent investigators. For each study we calculated the odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs. Results., Thirteen studies investigated the association between the MTHFR 677C>T polymorphism and migraine. The TT genotype was associated with an increased risk for any migraine, which only appeared for migraine with aura (pooled OR = 1.48, 95% CI 1.02-2.13), but not for migraine without aura. Nine studies investigated the association of the ACE D/I polymorphism with migraine. The II genotype was associated with a reduced risk for migraine with aura (pooled OR = 0.71, 95% CI 0.55-0.93) and migraine without aura (pooled OR = 0.84, 95% CI 0.70-0.99). Results for both variants were driven by studies in non-Caucasian populations. Results among Caucasians did not suggest an association. Extractable data did not allow investigation of gene,gene interactions. Conslusions., The MTHFR 677TT genotype is associated with an increased risk for migraine with aura, while the ACE II genotype is protective against both migraine with and without aura. Results for both variants appeared only among non-Caucasian populations. There was no association among Caucasians. [source] Common CX3CR1 Alleles Are Associated With a Reduced Risk of HeadachesHEADACHE, Issue 7 2008Christophe Combadière PhD Objectives., The aim of this study was to investigate the role of the chemokine receptor CX3CR1 in headaches and migraine. Methods., Distribution of 2 polymorphisms of the chemokine receptor CX3CR1 (V249I and T280M) was determined in a population-based sample of 1179 elderly individuals. Results., Heterozygotes for both CX3CR1 polymorphisms had a reduced risk of recurrent headaches, with an odds ratio (OR) of 0.64 (95% confidence interval [CI] = 0.46-0.90) for the I249 allele and 0.55 (95% CI = 0.38-0.81) for the M280 allele. Haplotype analysis showed that carriers of the rarer CX3CR1 I249-M280 haplotype had a reduced risk of recurrent headaches, with an OR of 0.57 (95% CI = 0.41-0.80, P = .001). This association was seen for both nonmigraine headaches (OR = 0.47, 95% CI = 0.28-0.79, P = .004) and migraine (OR = 0.65, 95% CI = 0.43-0.98, P = .041). Conclusions., These results need to be replicated but suggest that the chemokine receptor CX3CR1 may play a role in recurrent headaches. [source] Caffeine, cognitive failures and health in a non-working community sampleHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2009Andrew P Smith Abstract Rationale Most studies of the effects of caffeine on performance have been conducted in the laboratory and further information is required on the real-life effects of caffeine consumption on cognition. In addition, possible effects of caffeine consumption on a range of health outcomes should also be assessed in these studies to enable cost-benefit analyses to be conducted. Objectives Secondary analyses of a large epidemiological database (N,=,3223 non-working participants, 57% female, with a mean age of 49.6 years, range 17,92 years) were conducted to examine associations between caffeine consumption (mean caffeine consumption was 140,mg/day, range 0,1800,mg) and cognitive failures (errors of memory, attention and action) in a non-working sample. Associations between caffeine consumption and physical and mental health problems were also examined. Methods The study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. Associations between caffeine consumption and frequency of cognitive failures and health outcomes were examined in a sample of non-workers. Results After controlling for possible confounding factors significant associations between caffeine consumption and fewer cognitive failures were observed. Initial analyses suggested that many health variables were associated with regular level of caffeine consumption. However, most of the significant effects of caffeine disappeared when demographic and lifestyle factors were controlled for. Consumption of caffeine was, however, associated with a reduced risk of depression. These effects were also observed in separate analyses examining the source of the caffeine (coffee and tea). Conclusions Overall, the results show that caffeine consumption may benefit cognitive functioning in a non-working population. This confirms earlier findings from working samples. This beneficial effect of caffeine was not associated with negative health consequences. Indeed, consumption of caffeine was found to be associated with a reduced risk of depression. Copyright © 2008 John Wiley & Sons, Ltd. [source] Association of DLG5 variants with inflammatory bowel disease in the New Zealand caucasian population and meta-analysis of the DLG5 R30Q variant,INFLAMMATORY BOWEL DISEASES, Issue 9 2007Brian L. Browning PhD Abstract Background: Variants in the DLG5 gene have been associated with inflammatory bowel disease (IBD) in samples from some, but not all populations. In particular, 2 nonsynonymous single-nucleotide polymorphisms (SNPs), R30Q (rs1248696) and P1371Q (rs2289310), have been associated with an increased risk of IBD, and a common haplotype (called haplotype "A") has been associated with reduced risk. Methods: We genotyped R30Q, P1371Q, and a haplotype A tagging SNP (rs2289311) in a New Zealand Caucasian cohort of 389 Crohn's disease (CD) patients, 406 ulcerative colitis (UC) patients, and 416 population controls. Each SNP was tested for association with disease susceptibility and clinical phenotypes. We also performed a meta-analysis of R30Q data from published association studies. Results: The haplotype A tagging SNP was associated with reduced risk of IBD at the 0.05 significance level (P = 0.036) with an allelic odds ratio of 0.83 (95% confidence interval [CI]: 0.69,0.99). Association with haplotype A was strongest (odds ratio ,0.57) in UC patients with familial IBD or extraintestinal manifestations. The R30Q and P1371Q polymorphisms were not significantly associated with UC, CD, or IBD. Analysis of male and female data did not find any gender-specific associations. Meta-analysis gave no evidence of association of R30Q with IBD. Conclusions: Meta-analysis demonstrates that the minor allele of R30Q is not a risk factor for IBD across populations. This study provides some evidence that DLG5 haplotype A is associated with reduced risk of IBD in the New Zealand Caucasian population, but this association will need to be replicated in an independent sample. (Inflamm Bowel Dis 2007) [source] Risk factors for testicular cancer , differences between pure non-seminoma and mixed seminoma/non-seminoma?INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2006E. L. Aschim Summary The origin of testicular germ cell cancer (TGCC) is believed to be carcinoma in situ cells developed in utero. Clinically, TGCCs are divided into two major histological groups, seminomas and non-seminomas, where the latter group includes non-seminomatous TGCCs with seminomatous components (mixed S/NS TGCC). Recent studies, however, have suggested that non-seminomas and mixed S/NS TGCCs could have certain differences in aetiology, and in this study the TGCCs were divided into three, rather than the conventional two histological groups. A large case-control study was undertaken on data on all live-born boys registered in the Medical Birth Registry of Norway during the period 1967,1998 (n = 961 396). Among these were 1087 TGCC cases registered in the Cancer Registry of Norway until February 2004. We found several risk factors for TGCC, including low parity, low gestational age, epilepsy and retained placenta. Several of the variables studied seemed to be risk factors for specific histological groups, e.g. parity 0 vs. 2 and low gestational age being associated with increased risk of non-seminomas, but not of mixed S/NS TGCC, and low maternal age being associated with increased risk of mixed S/NS TGCC, but not of non-seminomatous TGCC. Therefore, our results might suggest that non-seminomas and mixed S/NS TGCCs have partially different risk factors, whose associations may be obscured by combining these two histological groups. The histological groups were not significantly different, however. Most of our findings on risk factors for TGCC are in agreement with at least some previous studies. An unexplainable exception is low birth weight being associated with reduced risk of TGCC in our study. [source] Citrus consumption and cancer incidence: the Ohsaki cohort studyINTERNATIONAL JOURNAL OF CANCER, Issue 8 2010Wen-Qing Li Abstract Basic research and case,control studies have suggested that citrus consumption may protect against cancer. However, the protective effect has been observed from few prospective studies. This study investigated the association of citrus consumption with cancer incidence among 42,470 Japanese adults in the Ohsaki National Health Insurance Cohort, which covered an age range of 40,79 years, and was followed up from 1995 to 2003 for all-cancer and individual cancer incidence. Citrus consumption was assessed using a self-administered questionnaire. The Cox proportional hazard model was applied to estimate relative risks (RRs) and 95% CIs. During the 323,204 person-years of follow-up, 3,398 cases were identified totally. Citrus consumption, especially daily consumption, was correlated with reduced all-cancer incidence, the RRs were 0.89 (95% CI = 0.80,0.98) for total participants, 0.86 (0.76,0.98) for males and 0.93 (0.79,1.09) for females, as well as multiple cancers at individual sites, especially pancreatic (RR = 0.62, 95% CI = 0.38,1.00) and prostate cancer (RR = 0.63, 95% CI = 0.41,0.97). Joint effect analysis showed a reduced risk of overall cancer existed only for subjects who consumed ,1 cup green tea/day (RR = 0.83, 95% CI = 0.73,0.93) as well as for males (RR = 0.83, 95% CI = 0.71,0.97) or females (RR = 0.82, 95% CI = 0.68,0.99). These findings suggest that citrus consumption is associated with reduced all-cancer incidence, especially for subjects having simultaneously high green tea consumption. Further work on the specific citrus constituents is warranted, and clinical trials are ultimately necessary to confirm the protective effect. [source] Biological indicators of prognosis in Ewing's sarcoma: An emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP)INTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Diana Zambelli Abstract Starting from an experimental model that accounts for the 2 most important adverse processes to successful therapy of Ewing's sarcoma (EWS), chemoresistance and the presence of metastasis at the time of diagnosis, we defined a molecular signature of potential prognostic value. Functional annotation of differentially regulated genes revealed 3 major networks related to cell cycle, cell-to-cell interactions and cellular development. The prognostic impact of 8 genes, representative of these 3 networks, was validated in 56 EWS patients. High mRNA expression levels of HINT1, IFITM2, LGALS3BP, STOML2 and c-MYC were associated with reduced risk to death and lower risk to develop metastasis. At multivariate analysis, LGALS3BP, a matricellular protein with a role in tumor progression and metastasis, was the most important predictor of event-free survival and overall survival. The association between LGALS3BP and prognosis was confirmed at protein level, when expression of the molecule was determined in tumor tissues but not in serum, indicating a role for the protein at local tumor microenvironment. Engineered enhancement of LGALS3BP expression in EWS cells resulted in inhibition of anchorage independent cell growth and reduction of cell migration and metastasis. Silencing of LGALS3BP expression reverted cell behavior with respect to in vitro parameters, thus providing further functional validation of genetic data obtained in clinical samples. Thus, we propose LGALS3BP as a novel reliable indicator of prognosis, and we offer genetic signatures to the scientific communities for cross-validation and meta-analysis, which are indispensable tools for a rare tumor such as EWS. [source] Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Su Dao Xiong Abstract Epidemiologic evidence suggests that a diet rich in fruits and vegetables is associated with a reduced risk of prostate cancer (PCa) development. Although several dietary compounds have been tested in preclinical PCa prevention models, no agents have been identified that either prevent the progression of premalignant lesions or treat advanced disease. Momordica charantia, known as bitter melon in English, is a plant that grows in tropical areas worldwide and is both eaten as a vegetable and used for medicinal purposes. We have isolated a protein, designated as MCP30, from bitter melon seeds. The purified fraction was verified by SDS-PAGE and mass spectrometry to contain only 2 highly related single chain Type I ribosome-inactivating proteins (RIPs), ,-momorcharin and ,-momorcharin. MCP30 induces apoptosis in PIN and PCa cell lines in vitro and suppresses PC-3 growth in vivo with no effect on normal prostate cells. Mechanistically, MCP30 inhibits histone deacetylase-1 (HDAC-1) activity and promotes histone-3 and -4 protein acetylation. Treatment with MCP30 induces PTEN expression in a prostatic intraepithelial neoplasia (PIN) and PCa cell lines resulting in inhibition of Akt phosphorylation. In addition, MCP30 inhibits Wnt signaling activity through reduction of nuclear accumulation of ,-catenin and decreased levels of c- Myc and Cyclin-D1. Our data indicate that MCP30 selectively induces PIN and PCa apoptosis and inhibits HDAC-1 activity. These results suggest that Type I RIPs derived from plants are HDAC inhibitors that can be utilized in the prevention and treatment of prostate cancer. © 2009 UICC [source] Genetic variation in the toll-like receptor gene cluster (TLR10-TLR1-TLR6) and prostate cancer riskINTERNATIONAL JOURNAL OF CANCER, Issue 11 2008Victoria L. Stevens Abstract Toll-like receptors (TLRs) are key players in the innate immune system and initiate the inflammatory response to foreign pathogens such as bacteria, fungi and viruses. The proposed role of chronic inflammation in prostate carcinogenesis has prompted investigation into the association of common genetic variation in TLRs with the risk of this cancer. We investigated the role of common SNPs in a gene cluster encoding the TLR10, TLR6 and TLR1 proteins in prostate cancer etiology among 1,414 cancer cases and 1,414 matched controls from the Cancer Prevention Study II Nutrition Cohort. Twenty-eight SNPs, which included the majority of the common nonsynonymous SNPs in the 54-kb gene region and haplotype-tagging SNPs that defined 5 specific haplotype blocks, were genotyped and their association with prostate cancer risk determined. Two SNPs in TLR10 [I369L (rs11096955) and N241H (rs11096957)] and 4 SNPs in TLR1 [N248S (rs4833095), S26L (rs5743596), rs5743595 and rs5743551] were associated with a statistically significant reduced risk of prostate cancer of 29,38% (for the homozygous variant genotype). The association of these SNPs was similar when the analysis was limited to cases with advanced prostate cancer. Haplotype analysis and linkage disequilibrium findings revealed that the 6 associated SNPs were not independent and represent a single association with reduced prostate cancer risk (OR = 0.55, 95% CI: 0.33, 0.90). Our study suggest that a common haplotype in the TLR10-TLR1-TLR6 gene cluster influences prostate cancer risk and clearly supports the need for further investigation of TLR genes in other populations. © 2008 Wiley-Liss, Inc. [source] Haplotype and genotypes of the VDR gene and cutaneous melanoma risk in non-Hispanic whites in Texas: A case,control studyINTERNATIONAL JOURNAL OF CANCER, Issue 9 2008Chunying Li Abstract In a hospital-based case,control study of 805 non-Hispanic whites with cutaneous melanoma and 841 cancer-free age-, sex- and ethnicity-matched control subjects, 3 VDR polymorphisms (i.e., TaqI, BsmI and FokI) were genotyped using blood samples collected between 1994 and 2006. We tested the hypothesis that the haplotypes and combined genotypes of these polymorphisms were associated with melanoma risk by interacting with known risk factors. Haplotypes t-B-F (adjusted odds ratio [OR], 0.52; 95% confidence interval [CI], 0.34,0.80) and t-B-f (adjusted OR, 0.51; CI, 0.27,0.94) were associated with a reduced risk when compared to T-b-f. The combined genotypes Tt+tt/Bb+BB/Ff+ff (adjusted OR, 0.69; CI, 0.52, 0.90) and Tt+tt/Bb+BB/FF (adjusted OR, 0.58; CI, 0.43, 0.78) were also associated with reduced risk, whereas the combined genotype TT/Bb+BB/Ff+ff genotype (adjusted OR, 2.35; CI, 1.13, 4.98) was associated with increased risk when compared to TT/bb/Ff+ff genotypes. On multivariate analysis, only the TaqI polymorphism was an independent risk factor, while the FokI polymorphism interacted with skin color (p = 0.029), moles (p = 0.017) and first-degree relatives with any cancer (p = 0.013) in modifying risk. Together, these findings suggest that VDR polymorphisms may directly affect or modify the risk associated with known melanoma risk factors. Larger, population-based studies are needed to replicate our findings. © 2008 Wiley-Liss, Inc. [source] Thymidylate synthase polymorphisms and colon cancer: Associations with tumor stage, tumor characteristics and survivalINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Karen Curtin Abstract Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. We investigated the role of functional polymorphisms in the TS 5,-UTR promoter enhancer region (TSER, 3 or 2 repeats of a 28-bp sequence) and the 3,-UTR (1494delTTAAAG) and their association with colon tumor characteristics, including tumor stage and acquired mutations in p53, Ki- ras and microsatellite instability. Data from a population-based incident case,control colon cancer study in northern California, Utah and Minnesota (1,206 cases, 1,962 controls) was analyzed using unordered polytomous logistic regression models. In both men and women, individuals with variant TS alleles were at reduced risk of having an advanced stage tumor (metastatic disease: OR = 0.35, 95% CI: 0.2,0.6 vs. wildtype TSER and 3,-UTR). Stage-adjusted survival did not differ by genotype. Men with 1 or 2 variant alleles in both the TSER and 3,-UTR genotypes had a 50% reduced risk of a p53 -positive tumor (OR = 0.5, 95% CI: 0.3,0.9 vs. homozygous wildtype TSER and 3,-UTR). Women with 1 or 2 variant alleles for either the TSER or 3,-UTR polymorphism had reduced risk of having any colon tumor that did not vary by mutation status. This study provides some support for associations between TS genotype and colon cancer tumor characteristics. © 2007 Wiley-Liss, Inc. [source] Risk for breast cancer among women with endometriosisINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Lisbeth Bertelsen Abstract Although several risk factors are common to endometriosis and breast cancer, the results of observational studies of an association have so far been inconsistent. We evaluated the relationship between endometriosis and breast cancer on the basis of data on selected cancers and medical histories from the Danish nationwide cancer and hospital registries used in a large case,cohort study. A total of 114,327 women were included in the study of whom 1,978 women had received a diagnosis of endometriosis and 16,983 had had a diagnosis of breast cancer between 1978 and 1998. Of the women with endometriosis, 236 subsequently received a diagnosis of breast cancer. The crude overall rate ratio for breast cancer after endometriosis was 1.00 and after adjustment for reproductive factors, calendar-period, bilateral oophorectomy and benign breast disease, the rate ratio was 0.97 (95% confidence interval, 0.85,1.11). The risk for breast cancer increased with age at diagnosis of endometriosis, so that women in whom endometriosis was diagnosed at a young age (approximately <40 years) had a reduced risk for breast cancer and women in whom endometriosis was diagnosed at older ages (approximately ,40 years) tended to have an increased risk for breast cancer. The reduced risks observed among young women may reflect their exposure to drugs with antiestrogenic effects. The increased risk associated with endometriosis among postmenopausal women may be due to common risk factors between postmenopausal endometriosis and breast cancer or an altered endogenous estrogen. © 2006 Wiley-Liss, Inc. [source] Dietary zinc, copper and selenium, and risk of lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 5 2007Somdat Mahabir Abstract Zinc, copper and selenium are important cofactors for several enzymes that play a role in maintaining DNA integrity. However, limited epidemiologic research on these dietary trace metals and lung cancer risk is available. In an ongoing study of 1,676 incident lung cancer cases and 1,676 matched healthy controls, we studied the associations between dietary zinc, copper and selenium and lung cancer risk. Using multiple logistic regression analysis, the odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for all subjects by increasing quartiles of dietary zinc intake were 1.0, 0.80 (0.65,0.99), 0.64 (0.51,0.81), 0.57 (0.42,0.75), respectively (p trend = 0.0004); similar results were found for men. For dietary copper, the ORs and 95% CI for all subjects were 1.0, 0.59 (0.49,0.73), 0.51 (0.41,0.64), 0.34 (0.26,0.45), respectively (p trend < 0.0001); similar reductions in risk and trend were observed by gender. Dietary selenium intake was not associated with risk, except for a significant inverse trend (p = 0.04) in men. Protective trends (p < 0.05) against lung cancer with increased dietary zinc intake were also found for all ages, BMI > 25, current smokers, pack-years ,30, light drinkers and participants without emphysema. Increased dietary copper intake was associated with protective trends (p < 0.05) across all ages, BMI, smoking and vitamin/mineral supplement categories, pack-years ,30 and 30.1,51.75 and participants without emphysema. Our results suggest that dietary zinc and copper intakes are associated with reduced risk of lung cancer. Given the known limitations of case,control studies, these findings must be interpreted with caution and warrant further investigation. © 2006 Wiley-Liss, Inc. [source] Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: Collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studiesINTERNATIONAL JOURNAL OF CANCER, Issue 4 2007Article first published online: 27 NOV 200 Abstract Squamous cell carcinomas account for about 80% of cancers of the uterine cervix, and the majority of the remainder are adenocarcinomas. There is limited evidence on the extent to which these histological types share a common etiology. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 8,097 women with invasive squamous cell carcinoma, 1,374 women with invasive adenocarcinoma and 26,445 women without cervical cancer (controls) from 12 epidemiological studies. Compared to controls, the relative risk of each histological type of invasive cervical cancer was increased with increasing number of sexual partners, younger age at first intercourse, increasing parity, younger age at first full-term pregnancy and increasing duration of oral contraceptive use. Current smoking was associated with a significantly increased risk of squamous cell carcinoma (RR = 1.50, 95% CI: 1.35,1.66) but not of adenocarcinoma (RR = 0.86 (0.70,1.05)), and the difference between the two histological types was statistically significant (case-case comparison p < 0.001). A history of screening (assessed as having had at least one previous nondiagnostic cervical smear) was associated with a reduced risk of both histological types, but the reduction was significantly greater for squamous cell carcinoma than for adenocarcinoma (RR = 0.46 (0.42,0.50) and 0.68 (0.56,0.82), respectively; case,case comparison, p = 0.002). A positive test for cervical high-risk HPV-DNA was a strong risk factor for each histological type, with 74% of squamous cell carcinomas and 78% of adenocarcinomas testing positive for HPV types 16 or 18. Squamous cell and adenocarcinoma of the cervix share most risk factors, with the exception of smoking. © 2006 Wiley-Liss, Inc. [source] MDM2 SNP309 T>G alone or in combination with the TP53 R72P polymorphism does not appear to influence disease expression and age of diagnosis of colorectal cancer in HNPCC patientsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Bente A. Talseth Abstract Disease expression in hereditary nonpolyposis colorectal cancer (HNPCC) cannot be readily explained by mutation site in the respective DNA mismatch repair genes associated with this disorder. One explanation is the role of modifying genes that can either promote or prevent disease development on a background of increased risk. Two single nucleotide polymorphisms in MDM2 and TP53 have been shown to be associated with younger ages of disease onset in HNPCC (TP53) and Li-Fraumeni syndrome (MDM2). In this study 220 HNPCC patients were examined, from Australia and Poland, all characterized at the molecular level to determine the frequency of the MDM2 SNP309 T>G and to assess its influence on disease expression. The results were then pooled with the results of a previous study to assess the combined influence of the MDM2 SNP309 T>G and TP53 SNP R72P. A significant difference was observed between CRC patients and unaffected MMR gene mutation carriers over the age of 45 years (p = 0.01). The unaffected MMR gene mutation carriers over the age of 45 years who carry the G allele have a reduced risk of developing CRC. The results indicate that the MDM2 SNP309, alone or in combination with TP53 R72P, does not influence age of diagnosis of CRC in individuals with HNPCC. In conclusion, the data indicates the G allele of MDM2 SNP309 might have a protective effect on disease development in HNPCC patients and that age of diagnosis of CRC is not associated with MDM2 SNP309 or TP53 R72P either as single SNPs or combined. © 2006 Wiley-Liss, Inc. [source] Ala394Thr polymorphism in the clock gene NPAS2: A circadian modifier for the risk of non-Hodgkin's lymphomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Yong Zhu Abstract Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non-Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer-related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population-based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51,0.85, p = 0.001), especially B-cell lymphoma (OR = 0.61, 95% CI: 0.47,0.80, p ,, 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation. © 2006 Wiley-Liss, Inc. [source] Impact of reproductive factors and lactation on breast carcinoma in situ riskINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Kathleen Meeske Abstract Incidence rates for breast carcinoma in situ (CIS) have increased markedly over the past 20 years. Breast CIS, detected primarily on mammography, now represents 30,45% of all screened detected breast cancers. We conducted a large population-based case-control study to evaluate the impact of reproductive factors and lactation on breast CIS risk. Case subjects were newly diagnosed with breast CIS at ages 35,64 years between March 1, 1995 and May 31, 1998 (n = 567), resided in Los Angeles County and were born in the United States. Control subjects (n = 614), identified through random digit dialing, fulfilled the same eligibility criteria and were required to have had at least one screening mammogram in the 2-year period before their interview. Women with a positive family history of breast cancer had a 2-fold increase in breast CIS risk. Parous women were at reduced risk relative to nulligravid women (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.46,1.00). Among nulliparous women, pregnancy was unrelated to breast CIS risk. Among parous women, risk declined with each additional term pregnancy (p -trend = 0.003). No associations were found with age at first term pregnancy, induced abortion or miscarriage. Long duration of breast-feeding (,24 months) was associated with increased risk (OR = 2.00, 95% CI = 1.11,3.60). The observed effects of family history and pregnancy on breast CIS risk are consistent with those observed for invasive breast cancer. The results for breast-feeding are contrary to what has been observed in studies of invasive breast cancer. © 2004 Wiley-Liss, Inc. [source] Abortions and breast cancer: Record-based case-control studyINTERNATIONAL JOURNAL OF CANCER, Issue 5 2003Gunnar Erlandsson Abstract It has been suggested that abortions leave the breast epithelium in a proliferative state with an increased susceptibility to carcinogenesis. Results from previous studies of induced or spontaneous abortions and risk of subsequent breast cancer are contradictory, probably due to methodological considerations. We investigated the relationship between abortions and subsequent breast cancer risk in a case-control study using prospectively recorded exposure information. The study population comprised women recorded in the population-based Swedish Medical Birth Register between 1973,91. Cases were defined by linkage of the birth register to the Swedish Cancer Register and controls were randomly selected from the birth register. From the subjects' antenatal care records we abstracted prospectively collected information on induced and spontaneous abortions, as well as a number of potential confounding factors. Relative risk of breast cancer was estimated by odds ratios (OR) with 95% confidence intervals (95% CI). A reduced risk of breast cancer was observed for women with a history of at least 1 compared to no abortions (adjusted OR = 0.84, 95% CI = 0.72,0.99). The adjusted OR decreases step-wise with number of abortions to 0.59 (95% CI = 0.34,1.03) for 3 or more compared to no abortions. The patterns are similar for induced and spontaneous abortions. In conclusion, neither a history of induced nor spontaneous abortions is associated with an increased risk of breast cancer. Our data suggest a protective effect of pregnancies regardless of outcome. © 2002 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||||||||