Heterogeneity In Risk Estimates Research Articles

Short-term associations between ground-level ozone exposure and urinary system disease hospital admissions through the emergency room in Beijing, China

BACKGROUND AND AIM: There is limited evidence on effects of ground-level ozone exposure on urinary system disease (USD). The aim of this study is to assess the association between short-term exposure to ground-level ambient ozone and risk of USD morbidity in Beijing, China. METHODS: We obtained data on daily average ozone concentrations from 35 fixed monitoring stations, and data on hospital admissions through the emergency room from secondary and tertiary hospitals in Beijing during 2013-2018. USD cases were extracted based on the primary diagnosis ICD-10 code (N00-N39). We estimated district-specific associations between ozone and daily counts of USD admissions on weekdays, using generalized linear models with a quasi-Poisson distribution and controlling for temperature and relative humidity in the model; and then pooled the district-specific estimates using random-effect meta-analysis. Lagged and cumulative effects were evaluated. Effect modification by season and confounding effects from co-pollutants (i.e., PM10, PM2.5, NO2, SO2, and CO) were assessed. RESULTS:We included 41,203 weekday USD admissions. An interquartile range increase of daily ozone exposure at lag 0 day was associated with 4.1% (95% confidence interval: 1.3%-6.9%) higher risk of USD admissions during the warm season (April to September), and was not associated with USD admission risk during the cool season (October to March), with no significant heterogeneity across districts. The heterogeneity of risk estimates between the warm and cool seasons was significant (I2=83%, Q=5.9, p-value=0.015). No lagged or cumulative associations were found. The association of warm-season ozone with risk of USD admissions was robust to adjustment for co-pollutants. CONCLUSIONS:Short-term exposure to higher ozone pollution is a risk factor for USD in Beijing during the warm season. This finding suggests that USD is a potential adverse health outcome of short-term ozone exposure. KEYWORDS: Ozone, short-term exposure, urinary system disease

Exogenous sex hormones, menstrual and reproductive history, and risk of non-melanoma skin cancer among women: a systematic literature review and meta-analysis

Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged < 40 years) have experienced steeper growth in their incidence rates in recent years. Hormonal factors were hypothesized to be playing a role in modulating NMSC risk, but the studies published to date provided conflicting results. We systematically reviewed and meta-analysed the studies focusing on the association between hormone-related characteristics (use of exogenous sex hormones, and aspects of menstrual and reproductive history) and the risk of NMSC among women. We included observational and experimental studies published in PubMed and EMBASE until February 2020. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) by applying random effects models with maximum likelihood estimation, and used the I2 statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88–1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87–1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women.

Evaluating the strength of evidence between long-term NO2 exposure and pediatric asthma incidence for potential inclusion into the Global Burden of Disease Study

Several epidemiological studies have highlighted a relationship between NO2 exposure and increased incidence and prevalence of pediatric asthma. Recently, the Global Burden of Disease (GBD) developed a quantitative evidence scoring approach with the intention to assess the effect and strength of the evidence for exposure-response relationships with consistency across all risk factors. We use this evidence scoring approach to generate a quantitative effect estimate for NO2 exposure and childhood asthma that can be applied for burden of disease assessments. For the purpose of this work, we systematically compiled existing studies on the relationship between NO2 and childhood asthma and extracted relative risks (RR). In addition, we extracted a set of study-specific covariates in order to explain between-study heterogeneity in risk estimates. We then applied the GBD’s newly developed meta-regression tool MR-BRT (MetaRegression - Bayesian, Regularized, Trimmed) to provide a quantitative estimate of effect and strength of evidence based upon unexplained between-study heterogeneity. Preliminary analyses including 28 sources from 11 countries identified within a systematic literature review conducted by Khreis et al. in 2017 were included in the metaregression. Overall, we estimated a RR of 1.10 (95% confidence interval [CI]=0.94-1.30) per 5 ppb increase in annual average NO2 (p-value=0.13) when not accounting for study-specific covariates. A model accounting for all significant study-level covariates (‘outcomes self-reported`, ‘confounding uncontrolled’, ‘selection bias’, and ‘subpopulation’) revealed an effect estimate of 1.28 (95%CI=1.00-1.63) per 5 ppb (p-value=0.024). Findings provide strong evidence for a relationship between NO2 exposure and pediatric asthma when adjusting for between-study heterogeneity. In future steps, we will include 27 additional studies that were published after the 2017 systematic review conducted by Khreis et al. (2017). Furthermore, we will apply an automated covariate selection process in which variables are sub-selected by running a set of log-linear models with a range of Lasso penalty parameters.

The effect of smoke-free legislation on the mortality rate of acute myocardial infarction: a meta-analysis

BackgroundSeveral studies have demonstrated that smoke-free legislation is associated with a reduced risk of mortality from acute myocardial infarction (AMI). This study aimed to examine and quantify the potential effect of smoke-free legislation on AMI mortality rate in different countries.MethodsStudies were identified using a systematic search of the scientific literature from electronic databases, including PubMed, Web of Science, ScienceDirect, Embase, Google Scholar, and China National Knowledge Infrastructure (CNKI), from their inception through September 30, 2017. A random effects model was employed to estimate the overall effects of smoke-free legislation on the AMI mortality rate. Subgroup analysis was performed to explore the possible causes of heterogeneity in risk estimates based on sex and age. The results of meta-analysis after excluding the studies with a high risk of bias were reported in this study.ResultsA total of 10 eligible studies with 16 estimates of effect size were included in this meta-analysis. Significant heterogeneity in the risk estimates was identified (overall I2 = 94.6%, p < 0.001). Therefore, a random effects model was utilized to estimate the overall effect of smoke-free legislation. There was an 8% decline in AMI mortality after introducing smoke-free legislation (RR = 0.92, 95% confidence interval (CI): 0.90–0.94). The results of subgroup analyses showed that smoke-free legislation was significantly associated with lower rates of mortality for the following 5 diagnostic subgroups: smoke-free in workplaces, restaurants and bars (RR = 0.92, 95% CI: 0.90–0.95), smaller sample size (RR = 0.92, 95% CI: 0.89–0.95), study location in Europe (RR = 0.90, 95% CI: 0.85–0.94), regional study area (RR = 0.92, 95% CI: 0.89–0.94), and no previous local smoke-free legislation (RR = 0.91, 95% CI: 0.90–0.93). However, there was not much difference in AMI mortality rates after the legislation between the longer (RR = 0.92, 95% CI: 0.86–0.98) and shorter follow-up duration subgroups (RR = 0.92, 95% CI: 0.89–0.94).ConclusionSmoke-free legislation could significantly reduce the AMI mortality rate by 8%. The reduction in the AMI mortality rate was more significant in studies with more comprehensive laws, without prior smoke-free bans, with a smaller sample size, at the regional level, and with a location in Europe.

Human exposure factors as potential determinants of the heterogeneity in city-specific associations between PM2.5 and mortality.

Multi-city population-based epidemiological studies of short-term fine particulate matter (PM2.5) exposures and mortality have observed heterogeneity in risk estimates between cities. Factors affecting exposures, such as pollutant infiltration, which are not captured by central-site monitoring data, can differ between communities potentially explaining some of this heterogeneity. This analysis evaluates exposure factors as potential determinants of the heterogeneity in 312 core-based statistical areas (CBSA)-specific associations between PM2.5 and mortality using inverse variance weighted linear regression. Exposure factor variables were created based on data on housing characteristics, commuting patterns, heating fuel usage, and climatic factors from national surveys. When survey data were not available, air conditioning (AC) prevalence was predicted utilizing machine learning techniques. Across all CBSAs, there was a 0.95% (Interquartile range (IQR) of 2.25) increase in non-accidental mortality per 10 µg/m3 increase in PM2.5 and significant heterogeneity between CBSAs. CBSAs with larger homes, more heating degree days, a higher percentage of home heating with oil had significantly (p < 0.05) higher health effect estimates, while cities with more gas heating had significantly lower health effect estimates. While univariate models did not explain much of heterogeneity in health effect estimates (R2 < 1%), multivariate models began to explain some of the observed heterogeneity (R2 = 13%).

The association between periodontal disease and the risk of myocardial infarction: a pooled analysis of observational studies

BackgroundSeveral meta-analyses have indicated that periodontal disease (PD) are related to cardiovascular diseases (CVDs). However, the association between PD and myocardial infarction (MI) remains controversial. Here we aimed to assess the association between PD and MI by meta-analysis of observational studies.MethodsPubMed, EMBASE and the Cochrane Library were searched through July, 2016. Observational studies including cohort, cross-sectional and case–control studies reporting odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CIs) were included in the analysis. Either fixed or random-effects model were applied to evaluate the pooled risk estimates. Sensitivity and subgroup analyses were also carried out to identify the sources of heterogeneity. Publication bias was assessed by the Begg’s, Egger’s test and funnel plot.ResultsWe included 22 observational studies with 4 cohort, 6 cross-sectional and 12 case–control studies, including 129,630 participants. Patients with PD have increased risk of MI (OR 2.02; 95% CI 1.59-2.57). Substantial heterogeneity in risk estimates was revealed. Subgroup analyses showed that the higher risk of MI in PD patients exists in both cross-sectional studies (OR 1.71; 95% CI 1.07-2.73) and case–control studies (OR 2.93; 95% CI 1.95-4.39), and marginally in cohort studies (OR 1.18; 95% CI 0.98-1.42). Further, subgroup meta-analyses by location, PD exposure, participant number, and study quality showed that PD was significantly associated with elevated risk of MI.ConclusionOur meta-analysis suggested that PD is associated with increased risk of future MI. However, the causative relation between PD and MI remains not established based on the pooled estimates from observational studies and more studies are warranted.

Household Air Pollution and Cardiovascular Disease Risk: Results from the Prospective Urban and Rural Epidemiological Study

Introduction: An estimated 2.9 million deaths in 2013 were attributable to exposure to household air pollution (HAP). The majority (52%) of this burden is from cardiovascular disease (CVD), yet to date no prospective study has examined HAP and CVD incidence. Here we investigate the association between HAP and CVD within the Prospective Urban and Rural Epidemiology (PURE) cohort. Methods: We examined 26 centers in the PURE study that reported greater than 10% solid fuel use for cooking, resulting in 97,350 participants with CVD follow-up across 10 countries (Bangladesh, Brazil, Chile, China, Colombia, India, Pakistan, South Africa, and Zimbabwe). Average follow-up in the cohort was 4.1 years, yielding 1,073 myocardial infarctions (MI), 878 strokes, 2,195 severe CVD events, 1,080 fatal CVD events, and 2,782 total deaths. We ran Cox-proportional hazards models, controlling for the INTERHEART risk score (a validated score for existing CVD risk-factors), urban/rural status, education, outdoor PM2.5, CVD medication use, country, and center. Results: We observed increases in risk of all-cause mortality (HR 1.16; 95% CI: 1.02-1.32) for individuals living in households with solid fuel use for cooking compared to electricity or liquefied petroleum gas (LPG). Increases (not statistically significant) in the risk of MI (7-20%), Stroke (9-46%) and Severe CVD (8-23%) were observed in models including all countries and in China/India models. The largest risks were observed in India. There was heterogeneity in risk estimates across study centers, although meta-analysis of these results were similar to overall models. Conclusions: In this large, multi-country prospective cohort we observed increases in all-cause mortality and CVD incidence for individuals living in households using solid fuel for cooking compared to electricity or LPG. Although effect sizes were modest, these results contribute the first direct evidence of an association between HAP and CVD incidence.

Molecular epidemiology study in Xuanwei: the relationship among coal type, genotype and lung cancer risk

背景与目的已有的研究证明：宣威是我国农村肺癌死亡率最高的地区，肺癌危险与室内燃烧烟煤产生的多环芳烃（polycyclic aromatic hydrocarbons, PAHs）有关，肺癌发病具有明显的地域性差别和家族聚集性。本研究从分子流行病学角度探索宣威肺癌风险的危险因素及与发病机理有关的基因型和燃煤类型。方法运用两个基于人群的病例对照研究，开展问卷调查，同时采集口腔细胞和痰等生物样品，提取DNA。应用PCR法检测GST超家族、AKR超家族和OGG1等基因型。通过Logistic回归分析煤种、基因型与肺癌风险的关联。结果与燃用无烟煤或木柴的研究对象相比，家用来宾烟煤的肺癌风险比数比（odds ratio, OR）值高达24.8，其次为龙潭（OR=11.6）、宝山（OR=6.0）、龙场（OR=4.1）、羊场（OR=3.8）等；燃用同种烟煤的男女肺癌风险相似。对于GSTM1缺失、AKR1C3（Ex1-70C > G）、OGG1（Ex6-315C > G）基因型，肺癌风险明显增高，且具统计学意义[OR（95%CI）分别为2.3（1.3-4.2）、1.8（1.0-3.5）和1.9（1.1-3.3）]。与家用烟煤量小且具GSTM1阳性的研究对象相比，用量大且GSTM1缺失的研究对象肺癌风险更高，女性OR为4.9（1.3-18.2），男性OR为2.7（1.0-7.4）。但对于AKR1C3（Ex1-70C > G）和OGG1（Ex6-315C > G），仅观察到女性肺癌风险的明显增高，OR分别为12.9（2.2-107.8）和5.7（1.1-34.2）。结论宣威不同煤种的肺癌风险有很大差异，但暴露于相同煤种的男性与女性肺癌风险相似。GSTM1缺失基因型与肺癌风险增高有关联。AKR1C3与OGG1这2种基因型与肺癌风险有关联，且在烟煤使用量高的女性中肺癌风险更高。

Prediagnostic serum tocopherol levels and the risk of non-hodgkin lymphoma: the multiethnic cohort.

Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high-pressure liquid chromatography/photodiode array detection with NHL risk. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). We observed U-shaped associations with NHL for total and α-tocopherols [Ptrend < 0.01 for polynomial terms (3 df)]. The ORs (95% CI) for total tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25-0.68), 0.52 (0.32-0.85), 0.39 (0.23-0.65), and 0.78 (0.47-1.29) for the second to fifth quintiles as compared with the first. The risk estimates were similar for α-tocopherol but nonsignificant for β- and γ-tocopherol combined and for γ-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than nonusers (21.32 ± 9.04 vs. 17.72 ± 7.43 μg/mL; P < 0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL.

The effects of smoke-free legislation on acute myocardial infarction: a systematic review and meta-analysis

BackgroundComprehensive smoke-free legislation has been implemented in many countries. The current study quantitatively examined the reduction in risk of acute myocardial infarction (MI) occurrence following the legislations and the relationship with the corresponding smoking prevalence decrease.MethodsPubMed, EMBASE, and Google Scholar databases and bibliographies of relevant studies and reviews were searched for potential original studies published from January 1, 2004, through October 31, 2011. Meta-analysis was performed using a random effect model to estimate the overall effects of the smoking-free legislations. Meta-regression was used to investigate possible causes of heterogeneity in risk estimates.ResultsA total of 18 eligible studies with 44 estimates of effect size were used in this study. Meta-analysis produced a pooled estimate of the relative risk of 0.87 (95% confidence interval (CI): 0.84 to 0.91). There was significant heterogeneity in the risk estimates (overall I2 = 96.03%, p<0.001). In meta-regression analysis, studies with greater smoking prevalence decrease produced larger relative risk (adjusted coefficient −0.027, 95% CI: -0.049 to −0.006, p=0.014).ConclusionSmoke-free legislations in public and work places were associated with significant reduction in acute MI risk, which might be partly attributable to reduced smoking prevalence.

Exposure to pesticides or solvents and risk of Parkinson disease

To investigate the risk of Parkinson disease (PD) associated with exposure to pesticides and solvents using meta-analyses of data from cohort and case-control studies. Prospective cohort and case-control studies providing risk and precision estimates relating PD to exposure to pesticides or solvents or to proxies of exposure were considered eligible. The heterogeneity in risk estimates associated with objective study quality was also investigated. A total of 104 studies/3,087 citations fulfilled inclusion criteria for meta-analysis. In prospective studies, study quality was not a source of heterogeneity. PD was associated with farming and the association with pesticides was highly significant in the studies in which PD diagnosis was self-reported. In case-control studies, study quality appeared to be a source of heterogeneity in risk estimates for some exposures. Higher study quality was frequently associated with a reduction in heterogeneity. In high-quality case-control studies, PD risk was increased by exposure to any-type pesticides, herbicides, and solvents. Exposure to paraquat or maneb/mancozeb was associated with about a 2-fold increase in risk. In high-quality case-control studies including an appreciable number of cases (>200), heterogeneity remained significantly high (>40%) only for insecticides, organochlorines, organophosphates, and farming; also, the risk associated with rural living was found to be significant. The literature supports the hypothesis that exposure to pesticides or solvents is a risk factor for PD. Further prospective and high-quality case-control studies are required to substantiate a cause-effect relationship. The studies should also focus on specific chemical agents.

Personality Disorders, Violence, and Antisocial Behavior: A Systematic Review and Meta-Regression Analysis

The risk of antisocial outcomes in individuals with personality disorder (PD) remains uncertain. The authors synthesize the current evidence on the risks of antisocial behavior, violence, and repeat offending in PD, and they explore sources of heterogeneity in risk estimates through a systematic review and meta-regression analysis of observational studies comparing antisocial outcomes in personality disordered individuals with controls groups. Fourteen studies examined risk of antisocial and violent behavior in 10,007 individuals with PD, compared with over 12 million general population controls. There was a substantially increased risk of violent outcomes in studies with all PDs (random-effects pooled odds ratio [OR] = 3.0, 95% CI = 2.6 to 3.5). Meta-regression revealed that antisocial PD and gender were associated with higher risks (p = .01 and .07, respectively). The odds of all antisocial outcomes were also elevated. Twenty-five studies reported the risk of repeat offending in PD compared with other offenders. The risk of a repeat offense was also increased (fixed-effects pooled OR = 2.4, 95% CI = 2.2 to 2.7) in offenders with PD. The authors conclude that although PD is associated with antisocial outcomes and repeat offending, the risk appears to differ by PD category, gender, and whether individuals are offenders or not.

The Impact of Saturable Metabolism on Exposure-Response Relations in 2 Studies of Benzene-induced Leukemia

Enzymatic saturation of metabolic pathways is one factor that potentially contributes to the nonlinear exposure-response relations that are frequently reported in occupational epidemiologic studies. The authors propose an approach to explore the contribution of saturable metabolism to previously reported exposure-response relations by integrating predictive models of relevant biomarkers of exposure into the epidemiologic analysis. The approach is demonstrated with 2 studies of leukemia in benzene-exposed workers, one conducted in the Australian petroleum industry (1981-1999) and one conducted in a US rubber hydrochloride production factory in Ohio (1940-1996). The studies differed greatly in their magnitudes and durations of exposure. Substitution of biomarker levels for external estimates of benzene exposure reduced the fold difference of the log relative risk of leukemia per unit of cumulative exposure between the 2 studies by 11%-44%. Nevertheless, a considerable difference in the log relative risk per unit of cumulative exposure remained between the 2 studies, suggesting that exposure misclassification, differences in study design, and potential confounding factors also contributed to the heterogeneity in risk estimates.

Comparison of exposure assessment methods for occupational carcinogens in a multi-centre lung cancer case–control study

ObjectivesRetrospective exposure assessment remains a problematic aspect of population-based case–control studies. Different methods have been developed, including case-by-case expert assessment and job–exposure matrices (JEM). The present analyses compare exposure prevalence...

Estimating the Attributable Fraction for Cancer: A Meta-analysis of Nevi and Melanoma

Epidemiologic research has shown convincingly that certain phenotypic attributes are associated with increased relative risks of melanoma. Although such findings have intrinsic utility, there have been few attempts to translate such knowledge into estimates of disease burden suitable for framing public health policy. We aimed to estimate the population attributable fraction (PAF) for melanoma associated with melanocytic nevi using relative risk estimates derived from a systematic review and meta-analysis. We identified eligible studies using citation databases, followed by manual review of retrieved references. Of 49 studies identified, 25 and 23, respectively, were included in meta-analyses of atypical and common nevi. For people with > or =1 atypical nevi, the summary relative risk was 3.63 (95% confidence interval, 2.85-4.62), with a PAF of 0.25. The relative risk increased by 1.017 (95% confidence interval, 1.014-1.020) for each common nevus; however, significant heterogeneity in risk estimates was observed. We estimated that 42% of melanomas were attributable to having > or =25 common nevi (PAF 25-49 nevi = 0.15; PAF > or =50 nevi = 0.27), whereas PAFs for low nevus counts were modest (PAF 0-10 nevi = 0.04; PAF 11-24 nevi = 0.07). We modeled PAF under scenarios of varying nevus prevalence; the highest melanoma burden was always among those with high nevus counts (PAF range of 0.31-0.62 for > or =25 common nevi). Patients with > or =25 common nevi and/or > or =1 atypical nevi are a high-risk group, which might be targeted for identification, screening, and education. This work is the necessary first step in designing targeted preventive strategies for melanoma, which must now be overlaid with information about cost and utility.

Variation in lung cancer risk by smoky coal subtype in Xuanwei, China

Lung cancer rates in Xuanwei County have been among the highest in China for both males and females and have been causally associated with exposure to indoor smoky (bituminous) coal emissions that contain very high levels of polycyclic aromatic hydrocarbons. There are numerous coal mines across the County. Although lung cancer risk is strongly associated with the use of smoky coal as a whole, variation in risk by smoky coal subtype has not been characterized as yet. We conducted a population-based case-control study of 498 lung cancer cases and 498 controls, individually matched to case subjects on age (+/-2 years) and sex to examine risk by coal subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) for coal subtype were calculated by conditional logistic regression, adjusting for potential confounders. Overall, smoky coal use was positively and statistically significantly associated with lung cancer risk, when compared with the use of smokeless coal or wood (OR = 7.7, 95% CI = 4.5-13.3). Furthermore, there was a marked heterogeneity in risk estimates for specific subtypes of smoky coal (test for heterogeneity: p = 5.17 x 10(-10)). Estimates were highest for coal of the Laibin (OR = 24.8, 95% CI = 12.4-49.6) and Longtan (OR = 11.6, 95% CI = 5.0-27.2) coal types and lower for coal from other subtypes. These findings strongly suggest that in Xuanwei and elsewhere, the carcinogenic potential of coal combustion products can exhibit substantial local variation by specific coal source.

Nonsteroidal Anti-inflammatory Drugs and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County

Nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a reduced risk of colon cancer; further epidemiologic data appear consistent for stomach and esophageal adenocarcinomas. Yet, data on potential confounding effects by upper gastrointestinal tract (UGI) disorders on adenocarcinomas of the UGI are limited. This study recruited newly diagnosed patients with esophageal adenocarcinoma (n = 220), gastric cardia adenocarcinoma (n = 277), or distal gastric adenocarcinoma (n = 441) as well as 1,356 control subjects in Los Angeles County. Unconditional multivariable logistic regression analyses were done to evaluate the association between regular NSAID use, at least two pills per week for 1 month, and these cancers. Duration of regular use of aspirin and non-aspirin NSAIDs was associated with reduced relative odds of distal gastric adenocarcinoma [>5 years use versus no regular use: odds ratio (OR), 0.61; 95% confidence interval, 0.40-0.92; P(trend) = 0.009] and esophageal adenocarcinoma (OR, 0.60; 95% confidence interval, 0.38-0.95; P(trend) = 0.04) in multivariable models that included history of UGI disorders and other potential confounding factors. Daily regular use was also associated with statistically significant reduced ORs of these two tumor types. No significant heterogeneity in risk estimates was noted after stratification by history of UGI disorders for any of the sites studied. However, irregular users of NSAIDs also had reduced risk of these cancers when compared with nonusers. Results from this study support an inverse association between regular NSAID use and risk of esophageal and distal gastric adenocarcinomas in individuals with and without a history of UGI disorders with long duration and daily use, providing the greatest risk reduction. Reduced risk in irregular users suggests that factors other than an effect on cyclooxygenase may also be important.

A polymorphism in the 3' untranslated region of the gene encoding prostaglandin endoperoxide synthase 2 is not associated with an increase in breast cancer risk: a nested case-control study

IntroductionProstaglandins are integral components in the cellular response to inflammation, promoting cellular proliferation and angiogenesis. The enzyme responsible for the conversion of arachidonic acid to prostaglandins in response to inflammation is prostaglandin endoperoxide synthase 2/cyclo-oxygenase 2 (PTGS2/COX2). Polymorphisms in the PTGS2 gene have been associated with various diseases, including inflammatory bowel disease and cancer of the lung, colorectum, and breast.MethodsWe genotyped the five most common polymorphisms (rs20417, rs5277, rs20432, rs5275, and rs4648298) in the Nurses' Health Study (1,270 cases, 1,762 controls) to test the hypothesis that polymorphisms in PTGS2 are associated with breast cancer risk, using logistic regression analyses. The Nurses' Health Study 2 (317 cases, 634 controls) and Harvard Women's Health Study (702 cases, 703 controls) were used to further examine putative associations.ResultsThe rs5275 polymorphism in the 3' untranslated region of the PTGS2 gene was associated with a decrease in breast cancer risk. We therefore genotyped this single-nucleotide polymorphism in the Nurses' Health Study 2 and Harvard Women's Health Study. Similar results were observed in these subsequent analyses, with no statistically significant heterogeneity in risk estimates between studies. In pooled analyses, women homozygous for the T allele at rs5275 had a 20% lower risk of breast cancer than those homozygous for the C allele (odds ratio 0.80, 95% confidence interval 0.66 to 0.97).ConclusionAlthough this polymorphism may be associated with a decrease in breast cancer risk among Caucasian women, we provide strong evidence that it is not associated with an increased risk of breast cancer.

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and α- and γ-tocopherol, with the risk of gastric adenocarcinoma in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and α-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma β-cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30–0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22–0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33–0.93, Ptrend=0.005) and lipid-unadjusted α-tocopherol (OR=0.59, 95% CI=0.37–0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted α-tocopherol (OR=0.26, 95% CI=0.11–0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and α-tocopherol are associated with reduced risk of GC.

The Effect of Ozone and PM10 on Hospital Admissions for Pneumonia and Chronic Obstructive Pulmonary Disease: A National Multicity Study

A case-crossover study was conducted in 36 US cities to evaluate the effect of ozone and particulate matter with an aerodynamic diameter of < or =10 microm (PM10) on respiratory hospital admissions and to identify which city characteristics may explain the heterogeneity in risk estimates. Respiratory hospital admissions and air pollution data were obtained for 1986-1999. In a meta-analysis based on the city-specific regression models, several city characteristics were evaluated as effect modifiers. During the warm season, the 2-day cumulative effect of a 5-ppb increase in ozone was a 0.27% (95% confidence interval (CI): 0.08, 0.47) increase in chronic obstructive pulmonary disease admissions and a 0.41% (95% CI: 0.26, 0.57) increase in pneumonia admissions. Similarly, a 10-microg/m(3) increase in PM10 during the warm season resulted in a 1.47% (95% CI: 0.93, 2.01) increase in chronic obstructive pulmonary disease at lag 1 and a 0.84% (95% CI: 0.50, 1.19) increase in pneumonia at lag 0. Percentage of households with central air conditioning reduced the effect of air pollution, and variability of summer apparent temperature reduced the effect of ozone on chronic obstructive pulmonary disease. The study confirmed, in a large sample of cities, that exposure to ozone and PM10 is associated with respiratory hospital admissions and provided evidence that the effect of air pollution is modified by certain city characteristics.