Moderate Relative Risk Research Articles

Vascular aging in the young: New carotid stiffness centiles and association with general and abdominal obesity – The KIGGS cohort

Background and aimsThe evidence for an association between obesity and increased carotid intima-media thickness (CIMT) and carotid stiffness (CS) in the young has been limited by methodological challenges related to study populations, measurements, methods of percentile derivation and comprehensiveness of obesity markers investigated. This nationwide general population study developed new CS and CIMT centiles in the young and used them to study associations with body mass index, waist circumference, waist-to-height-ratio, bioimpedance-derived absolute and relative fat mass, fat-free mass, subscapular skinfold thickness and blood pressure. MethodsIn its 11-year follow-up, the KiGGS cohort, which is based on a nationally representative sample, included semi-automated state-of-the-art sonographic CIMT and CS measurements in 4,709 participants aged 14 to 28. Distensibility coefficient (DC), stiffness index β, Young's elastic modulus (YEM) and Peterson's elastic modulus (Ep) centiles were modelled by sex, age and height simultaneously. ResultsCS increased with age in both sexes, and young men had stiffer arteries than young women at all ages. All obesity measures at baseline and at follow-up, except for subscapular skinfold thickness, were positively associated with several CS parameters with moderate relative risks (RR), e.g. cross-sectional RR 2.23 (95% CI 1.26–3.93) for DC ≥ 90th percentile when waist circumference ≥90th percentile; RR 5.98 (3.38–10.56) for elevated DC associated with simultaneously elevated waist circumference and BP. ConclusionsThese new state-of-the-art CS percentiles show consistent associations of obesity with CS in the young and support primary prevention efforts starting at a young age.

Estimation of long-term and short-term health effects attributed to PM2.5 standard pollutants in the air of Ardabil (using Air Q + model).

Clean air is considered as a basic need for human health. However, air pollution is a significant threat to health in developed and developing countries. The aim of this study was to estimate the health effects attributed to PM2.5 pollutants in the air of Ardabil in 2018 (using Air Q + model). Raw data related to particles were collected from the Department of Environment and processed in Excel software and converted into an input file of the Air Q + model, and in the final stage, by considering appropriate epidemiological parameters and combining these data with air quality data, it was possible to estimate the health effects of air pollution. The results showed that the average annual concentrations of PM2.5 and PM10 were 15.47 and 30.94 in the study year, respectively. The total number of deaths due to ALRI, COPD, lung cancer, IHD, and stroke deaths on average during the study period were estimated to be 73, 11, 7, 15, and 14 deaths, respectively, which include 14.62, 15.78, 4.9, 12.43, and 11.6% of deaths due to ALRI, COPD, lung cancer, IHD, and stroke deaths, respectively. In conditions of concentration above 5µg/m3, attributed proportion, total number of attributed cases and number of attributed cases per 100,000 population (with moderate relative risk and confidence interval of 95%) for cardiovascular diseases have been estimated to be 0.95% 103 people and 42.19 people. Also, the attributed proportion, the total number of attributable cases, and the number of attributable cases per 100,000 population (with moderate relative risk and confidence of 95%) for the admission of respiratory diseases have been estimated at 97.1%, 68 persons and 3 persons, respectively. Our results suggest that particle exposure even at low concentrations is associated with an increased risk of overall mortality and specific cause mortality and hospital admissions for respiratory and cardiovascular diseases.

Aortic stiffness and content of adipokines in the serum in persons of European and South Asian ethnic

To evaluate the cardiovascular risk (CVR) based on arterial stiffness and content of adipokines in young-aged persons of different ethnicity (European and South Asian). 290 persons of European (Slavic) and South Asian (Korean) ethnicity aged from 19 to 49 years with and without arterial hypertension (AH) were examined. Clinical, anthropometric, laboratory examinations were performed, levels of resistin and adiponectin of blood were assessed. Total CVR was assessed by SCORE scale, patients under the age of 40 years were assessed by relative risk scale. Aortic stiffness was examined by non-invasive arteriography. Patients of European ethnicity had higher blood pressure (BP), body mass index (BMI), waist circumference (WC), levels of resistin and adiponectin. Pulse wave velocity in the aorta (PWVA) did not differ significantly in ethnic groups. According to the SCORE scale in individuals of the European and South Asian races in general groups and groups with arterial hypertension a moderate absolute risk was determined, in individuals under 40 years of age a moderate relative risk was determined without a significant difference between the groups. However increased levels of PWVA (more than 10 m/s) were registered more often in Korean ethnicity (46.9% compared to Slavic ethnicity, 22.2%). Closer reliable correlations between the level of BP and BMI, WC, PWVA were revealed in Korean ethnicity. Ethnic differences in correlation of adipokines in blood and their dependence on anthropometric and hemodynamic characteristics were described. The assessment of CVR according to traditional scales does not always accurately represent its real level. New information was obtained on the features of adipokine metabolism and its connections with early manifestations of vascular remodeling in young-aged depending on the race. Taking into account ethnic differences, we recommend in-depth diagnostics of CVR in South Asians. The data can be useful for the design of personalized programs for the diagnostics and assessment of CVR.

The aptamer BT200 effectively inhibits von Willebrand factor (VWF) dependent platelet function after stimulated VWF release by desmopressin or endotoxin

Von Willebrand factor (VWF) plays a major role in arterial thrombosis. Antiplatelet drugs induce only a moderate relative risk reduction after atherothrombosis, and their inhibitory effects are compromised under high shear rates when VWF levels are increased. Therefore, we investigated the ex vivo effects of a third-generation anti-VWF aptamer (BT200) before/after stimulated VWF release. We studied the concentration-effect curves BT200 had on VWF activity, platelet plug formation under high shear rates (PFA), and ristocetin-induced platelet aggregation (Multiplate) before and after desmopressin or endotoxin infusions in healthy volunteers. VWF levels increased > 2.5-fold after desmopressin or endotoxin infusion (p < 0.001) and both agents elevated circulating VWF activity. At baseline, 0.51 µg/ml BT200 reduced VWF activity to 20% of normal, but 2.5-fold higher BT200 levels were required after desmopressin administration (p < 0.001). Similarly, twofold higher BT200 concentrations were needed after endotoxin infusion compared to baseline (p < 0.011). BT200 levels of 0.49 µg/ml prolonged collagen-ADP closure times to > 300 s at baseline, whereas 1.35 µg/ml BT200 were needed 2 h after desmopressin infusion. Similarly, twofold higher BT200 concentrations were necessary to inhibit ristocetin induced aggregation after desmopressin infusion compared to baseline (p < 0.001). Both stimuli elevated plasma VWF levels in a manner representative of thrombotic or pro-inflammatory conditions such as arterial thrombosis. Even under these conditions, BT200 potently inhibited VWF activity and VWF-dependent platelet function, but higher BT200 concentrations were required for comparable effects relative to the unstimulated state.

Effects of Socio-Environmental Factors on Malaria Infection in Pakistan: A Bayesian Spatial Analysis.

The role of socio-environmental factors in shaping malaria dynamics is complex and inconsistent. Effects of socio-environmental factors on malaria in Pakistan at district level were examined. Annual malaria cases data were obtained from Directorate of Malaria Control Program, Pakistan. Meteorological data were supplied by Pakistan Meteorological Department. A major limitation was the use of yearly, rather than monthly/weekly malaria data in this study. Population data, socio-economic data and education score data were downloaded from internet. Bayesian conditional autoregressive model was used to find the statistical association of socio-environmental factors with malaria in Pakistan. From 136/146 districts in Pakistan, >750,000 confirmed malaria cases were included, over a three years’ period (2013–2015). Socioeconomic status ((posterior mean value −3.965, (2.5% quintile, −6.297%), (97.5% quintile, −1.754%)) and human population density (−7.41 × 10−4, −0.001406%, −1.05 × 10−4 %) were inversely related, while minimum temperature (0.1398, 0.05275%, 0.2145%) was directly proportional to malaria in Pakistan during the study period. Spatial random effect maps presented that moderate relative risk (RR, 0.75 to 1.24) and high RR (1.25 to 1.99) clusters were scattered throughout the country, outnumbering the ones’ with low RR (0.23 to 0.74). Socio-environmental variables influence annual malaria incidence in Pakistan and needs further evaluation.

On the Gains of Using High Frequency Data in Portfolio Selection

Abstract This paper analyzes empirically the performance gains of using high frequency data in portfolio selection. Assuming Constant Relative Risk Aversion (CRRA) preferences, with different relative risk aversion levels, we compare low and high frequency portfolios within mean-variance, mean-variance-skewness and mean-variance-skewness-kurtosis frameworks. Using data on fourteen stocks of the Euronext Paris, from January 1999 to December 2005, we conclude that the high frequency portfolios outperform the low frequency portfolios for every out-of-sample measure, irrespectively to the relative risk aversion coefficient considered. The empirical results also suggest that for moderate relative risk aversion the best performance is always achieved through the jointly use of the realized variance, skewness and kurtosis. This claim is reinforced when trading costs are taken into account.

Association of anticardiolipin, antiphosphatidylserine, anti-β2 glycoprotein I, and antiphosphatidylcholine autoantibodies with canine immune thrombocytopenia.

BackgroundIn humans, the presence of antiphospholipid antibodies (aPL) is frequently found in immune thrombocytopenia. The present study investigated whether aPL and any aPL subtypes are associated with canine thrombocytopenia, in particular, immune-mediated thrombocytopenia (immune thrombocytopenia) that usually manifests with severe thrombocytopenia.ResultsSera were collected from 64 outpatient dogs with thrombocytopenia (Group I, platelet count 0 – 80 × 103/uL), and 38 of which having severe thrombocytopenia (platelet count < 30 × 103/uL) were further divided into subgroups based on the presence of positive antiplatelet antibodies (aPLT) (subgroup IA, immune thrombocytopenia, n =20) or the absence of aPLT (subgroup IB, severe thrombocytopenia negative for aPLT, n =18). In addition, sera of 30 outpatient dogs without thrombocytopenia (Group II), and 80 healthy dogs (Group III) were analyzed for comparison. Indirect ELISAs were performed to compare serum levels of aPL subtypes, including anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), antiphosphatidylcholine (aPC), and anti-β2 glycoprotein I antibodies (aβ2GPI), and antiphosphatidylinositol antibodies (aPI), among different groups or subgroups of dogs. Among outpatient dogs, aCL, being highly prevalent in outpatient dogs with thrombocytopenia (63/64, 98 %), is an important risk factor for thrombocytopenia (with a high relative risk of 8.3), immune thrombocytopenia (relative risk 5.3), or severe thrombocytopenia negative for aPLT (relative risk ∞, odds ratio 19). In addition, aPS is a risk factor for immune thrombocytopenia or severe thrombocytopenia negative for aPLT (moderate relative risks around 2), whereas aPC and aβ2GPI are risk factors for immune thrombocytopenia (relative risks around 2).ConclusionsOf all the aPL subtypes tested here, aCL is highly associated with canine thrombocytopenia, including immune thrombocytopenia, severe thrombocytopenia negative for aPLT, and less severe thrombocytopenia. Furthermore, aPS is moderately associated with both canine immune thrombocytopenia and severe thrombocytopenia negative for aPLT, whereas aβ2GPI, and aPC are moderately relevant to canine immune thrombocytopenia. In contrast, aPI is not significantly associated with canine immune thrombocytopenia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0727-3) contains supplementary material, which is available to authorized users.

Earthquake Hazard Zonation and Seismotectonics of the Bandar Abbas Area, Zagros, Iran

The study area (Bandar Abbas area) is located in the Zagros fold-thrust belt as part of the Alpine-Himalayan orogenic belt as seismically active belt. This area is located between the Makran accretionary prism and Oman Mountains from east and the Zagros collision belt from west as transition zone. The Zagros fold-thrust belt from the viewpoint of seismicity, is very active and Iran’s major earthquake-prone area. The study area has main active faults and some high magnitude earthquakes occurred in current century. Because the Bandar Abbas area has high seismic activity, the main goal of this research is prepared to earthquake hazard zonation and identify hazardous seismic zones, based on Decision Support System method for define active seismotectonic in this area. The seismotectonic study has been done in 30 - 100 km radius, for Bandar Abbas area. In this research, we used Decision Support System method by in corporate and combine essential data such as seismic data from 1900-2015, Digital Elevation Model of the study area (DEM), surface geology, seismicity parameters, soil classification and location main faults. In this research the Decision Support System (DSS) base on GIS database is used for calculate seismicity parameters. Based on the relative risk of earthquake zonation map, the Bandar Abbas area is located from the north to the East and from the South to the East, in area with high seismic risk (with Orange color). Some small regions with very high relative seismic risk have been limited to these areas with high risk. Also from north to west and from south to west “the study area” is located mainly in the area with earthquake relative risk of in areas with moderate and low relative risk of earthquakes. In the far southwestern region of the study, the small area is located in an area with high and very high seismic relative risk and this case may be due to the activity of the Mountain Front Fault (MFF) and Zagros Fore deep Fault (ZFF). Finally, the study area has been affected by active faults and it causes high vulnerability of the study area in the face of a possible occurrence of earthquakes. Based on of Seismotectonic investigations, there are existed minor faults of the Zagros fault from East to West and in the middle part. This case has been caused some parts in the study area with low and moderate seismic risk to be considered in the face of possible earthquakes and seismic damages, as an area with high seismic risk.

Authors' response: Understanding variation in disease risk.

Authors' response: Understanding variation in disease risk.

Understanding variation in disease risk: the elusive concept of frailty.

The concept of frailty plays a major role in the statistical field of survival analysis. Frailty variation refers to differences in risk between individuals which go beyond known or measured risk factors. In other words, frailty variation is unobserved heterogeneity. Although understanding frailty is of interest in its own right, the literature on survival analysis has demonstrated that existence of frailty variation can lead to surprising artefacts in statistical estimation that are important to examine. We present literature that demonstrates the presence and significance of frailty variation between individuals. We discuss the practical content of frailty variation, and show the link between frailty and biological concepts like (epi)genetics and heterogeneity in disease risk. There are numerous suggestions in the literature that a good deal of this variation may be due to randomness, in addition to genetic and/or environmental factors. Heterogeneity often manifests itself as clustering of cases in families more than would be expected by chance. We emphasize that apparently moderate familial relative risks can only be explained by strong underlying variation in disease risk between families and individuals. Finally, we highlight the potential impact of frailty variation in the interpretation of standard epidemiological measures such as hazard and incidence rates.

Mammographic density is not a worthwhile examination to distinguish high cancer risk women in screening

Numerous studies established high mammographic density (MD) as a significant breast cancer risk. By adopting both radiological and epidemiological perspectives, we analysed the capacity of this radiological parameter to express an individual level of risk and the methods for assessing the relationship between MD categories and risk. MD is unable to identify individual underlying anatomical and physiological components. Many factors affect accurate and reproducible measurements and consequently classifications of MD. Significant relative risks were found by comparing the MD categories in the tails of distribution (i.e. the group of women with the lowest MD to that with the highest MD), which represent <10% of women in each group: the majority of the population was ignored. When a relevant threshold of MD was applied to compare another group and the entire population was included to compare the two groups, some studies showed no significant or only moderate relative risk (RR) between women with readings above and those below the threshold. Sensitivity and specificity remain unknown. MD cannot be considered a worthwhile test by which to categorically identify high-risk women in screening. Key points • Unknown individual anatomical and physiological components do not express the risk level.• The epidemiological conditions are not relevant to distinguish a high-risk category.• The most relevant studies show no or moderate risks.

Resting State Electroencephalogram Oscillatory Abnormalities in Schizophrenia and Psychotic Bipolar Patients and Their Relatives from the Bipolar and Schizophrenia Network on Intermediate Phenotypes Study

Abnormal resting state electroencephalogram (EEG) oscillations are reported in schizophrenia (SZ) and bipolar disorder, illnesses with overlapping symptoms and genetic risk. However, less evidence exists on whether similar EEG spectral abnormalities are present in individuals with both disorders or whether these abnormalities are present in first-degree relatives, possibly representing genetic predisposition for these disorders. Investigators examined 64-channel resting state EEGs of 225 SZ probands and 201 first-degree relatives (SZR), 234 psychotic bipolar (PBP) probands and 231 first-degree relatives (PBPR), and 200 healthy control subjects. Eight independent resting state EEG spectral components and associated spatial weights were derived using group independent component analysis. Analysis of covariance was conducted on spatial weights to evaluate group differences. Relative risk estimates and familiality were evaluated on abnormal spectral profiles in probands and relatives. Both SZ and PBP probands exhibited increased delta, theta, and slow and fast alpha activity. Post-hoc pair-wise comparison revealed increased frontocentral slow beta activity in SZ and PBP probands as well as SZR and PBPR. Augmented frontal delta activity was exhibited by SZ probands and SZR, whereas PBP probands and PBPR showed augmented fast alpha activity. Both SZ and PBP probands demonstrated aberrant low-frequency activity. Slow beta activity was abnormal in SZ and PBP probands as well as SZR and PBPR perhaps indicating a common endophenotype for both disorders. Delta and fast alpha activity were unique endophenotypes for SZ and PBP probands, respectively. The EEG spectral activity exhibited moderate relative risk and heritability estimates, serving as intermediate phenotypes in future genetic studies for examining biological mechanisms underlying the pathogenesis of the two disorders.

Logistic Regression for Extremely Rare Events: The Case of School Shootings

School shootings are often used in public policy debate as a justification for increased regulation, based on qualitative arguments. However, to date, no effort has been made to find valid quantitative evidence for the claims bolstering the regulation recommendations. In defense of this absence of evidence, it is usually argued that the rarity of such events does not allow the employment of quantitative methods. This paper, using a simulation study, shows that, based on the number of school shootings in the United States and Germany combined, the well-known method of logistic regression can be applied to a case-control study, making it possible to at least test for an association between hypothesized influential variables and the occurrences. Moderate relative risks, explained by an observed variable, would lead to a high power of the appropriate test. A moderate numbers of cases generated by such a variable would suffice to show a significant association.

Winter time particulate matter concentrations at an urban roadway in India

This paper presents analysis and interpretation of 1-hr average fine (PM1 and PM2.5) and coarse (PM10) particulate matter (PM) concentrations measured during winter 2008 and 2009 at a roadside in Chennai city, India. Results showed typical weekly and diurnal cycles with high concentrations corresponding morning and evening peak traffic flows. The 24-hr average PM10 and PM2.5 concentrations were found to be 135 ± 65 and 73 ± 39 μg/m3 in winter 2008 and 131 ± 75 and 67 ± 32 μg/m3 in winter 2009, respectively and were violating the NAAQS (PM10 = 100 μg/m3; PM2.5 = 60 μg/m3) and WHO (PM10 = 50 μg/m3; PM2.5 = 25 μg/m3) limits. The daily PM1 concentrations at the study site were in the range of 11–200 (mean = 56) μg/m3. The estimated mortality relative risks associated with daily PM concentrations showed a high (81–85%) and moderate (42–48%) relative risks for PM10 and PM2.5, respectively, at the study site.

Factors associated with achievement and durability of cytogenetic response in patients with chronic myeloid leukemia treated with imatinib

Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has revolutionized the treatment of Bcr-Abl positive chronic myeloid leukemia and become the standard of care for this disease. The aim of this study was evaluation and analysis of cytogenetic response in different intervals and risk groups as well as finding association between pre-treatment characteristics and later probability of achievement of major cytogenetic response. We analyzed a total of 22 adult patients with newly diagnosed Philadelphia positive early chronic phase chronic myeloid leukemia treated at our institution from June 2006 to December 2009. The median follow-up time for patients during treatment with imatinib was 25.7 months (range, 12-42 months). A complete hematologic response was achieved in all of the analyzed patients within 6 months from the start of the treatment. The major cytogenetic response rate was 81.8%, and the complete cytogenetic response rate was 72.7%. The patients with low or moderate relative risk had the rate of complementary achieving major and complete cytogenetic response of 75-90%. A multivariate analysis identified the following independent prognostic factors for achieving major cytogenetic response: the absence of splenomegaly, white blood cell count less than 10 x 10(9)/L, the platelet count less than 450 x 10(9)/L, the presence of less than 5% of bone marrow blasts and basophils, the absence of blasts in peripheral blood, the presence of less than 7% of basophils in peripheral blood. Patients who early achieve complete and major cytogenetic response as well as those with low and moderate relative risk have a higher rate of achieving and maintaining complete cytogenetic response. There are also characteristics of patients before treatment that may indicate the treatment outcome.

Relative Risk of Probabilistic Category Learning Deficits in Patients with Schizophrenia and Their Siblings

Although patients with schizophrenia display an overall probabilistic category learning performance deficit, the extent to which this deficit occurs in unaffected siblings of patients with schizophrenia is unknown. There are also discrepant findings regarding probabilistic category learning acquisition rate and performance in patients with schizophrenia. A probabilistic category learning test was administered to 108 patients with schizophrenia, 82 unaffected siblings, and 121 healthy participants. Patients with schizophrenia displayed significant differences from their unaffected siblings and healthy participants with respect to probabilistic category learning acquisition rates. Although siblings on the whole failed to differ from healthy participants on strategy and quantitative indexes of overall performance and learning acquisition, application of a revised learning criterion enabling classification into good and poor learners on the basis of individual learning curves revealed significant differences between percentages of sibling and healthy poor learners: healthy (13.2%), siblings (34.1%), patients (48.1%), yielding a moderate relative risk. These results clarify previous discrepant findings pertaining to probabilistic category learning acquisition rate in schizophrenia and provide the first evidence for the relative risk of probabilistic category learning abnormalities in unaffected siblings of patients with schizophrenia, supporting genetic underpinnings of probabilistic category learning deficits in schizophrenia. These findings also raise questions regarding the contribution of antipsychotic medication to the probabilistic category learning deficit in schizophrenia. The distinction between good and poor learning might be used to inform genetic studies designed to detect schizophrenia risk alleles.

Narrowing the boundaries of the genetic architecture of schizophrenia.

Genetic architecture of a disease comprises the number, frequency, and effect sizes of genetic risk alleles and the way in which they combine together. Before the genomic revolution, the only clue to underlying genetic architecture of schizophrenia came from the recurrence risks to relatives and the segregation patterns within families. From these clues, very simple genetic architectures could be rejected, but many architectures were consistent with the observed family data. The new era of genome-wide association studies can provide further clues to the genetic architecture of schizophrenia. We explore models of genetic architecture by description rather than the mathematics that underpins them. We conclude that the new genome-wide data allow us to narrow the boundaries on the models of genetic architecture that are consistent with the observed data. A genetic architecture of many common variants of moderate (relative risk > approximately 1.2) can be excluded, yet there is evidence that current generation genome-wide chips do tag an important proportion of the genetic variation for schizophrenia and that the underlying causal variants will include common variants of small effect as well as rarer variants of larger effect. Together, these observations imply that the total number of genetic variants is very large—of the order of thousands. The first generation of studies have generated hypotheses that should be testable in the near future and will further narrow the boundaries on genetic architectures that are consistent with empirical data.

Proton Pump Inhibitor and Clopidogrel Interaction: Fact or Fiction?

Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. Clopidogrel is converted to its active metabolite by cytochrome P450 (CYP) enzymes. Clopidogrel users with decreased CYP2C19 function have less inhibition of platelet aggregation and increased cardiovascular (CV) events. As PPI metabolism also involves CYP2C19, it was hypothesized that competition by PPIs might interfere with clopidogrel's action. Omeprazole, but not other PPIs, worsens surrogate markers of clopidogrel efficacy. Some (but not all) observational studies show that clopidogrel users prescribed PPIs have increased risks of CV events (hazard/odds ratios=1.25-1.5). When effect sizes are small to moderate (relative risks<1.5-2.0), however, it is only possible to conclude whether statistical associations are valid in randomized trials. A randomized trial of omeprazole vs. placebo in clopidogrel users showed no difference in CV events (hazard ratio=1.02,0.70-1.51). Thus, current evidence does not justify a conclusion that PPIs are associated with CV events among clopidogrel users, let alone a judgment of causality. Nonetheless, positive results from some observational studies and biological plausibility have led some health-care providers to accept that PPIs reduce clopidogrel's efficacy. The US Food and Drug Administration (FDA) recommends that "concomitant use of drugs that inhibit CYP2C19 (e.g., omeprazole) should be discouraged." As the presence of PPIs and clopidogrel in plasma is short lived, separation by 12-20 h should in theory prevent competitive inhibition of CYP metabolism and minimize any potential, though unproven, clinical interaction. PPI may be given before breakfast and clopidogrel at bedtime, or PPI may be taken before dinner and clopidogrel at lunchtime.

Analysis of Recently Identified Prostate Cancer Susceptibility Loci in a Population-based Study: Associations with Family History and Clinical Features

Two recent genome-wide association studies have highlighted several single nucleotide polymorphisms (SNPs) purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and the clinicopathologic features of the disease. We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk stratified by family history of prostate cancer and clinicopathologic features of the disease was calculated with the use of logistic and polytomous regression. These results confirm the importance of multiple, previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude with that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, whereas risk estimates for rs10993994 and rs5945619 varied by Gleason score. Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however, the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features.

Gauging the Performance of SNPs, Biomarkers, and Clinical Factors for Predicting Risk of Breast Cancer

Gauging the Performance of SNPs, Biomarkers, and Clinical Factors for Predicting Risk of Breast Cancer