Methods for pooling results of epidemiologic studies: the Pooling Project of Prospective Studies of Diet and Cancer

University of Toronto, Toronto, Ontario, Canada
American Journal of Epidemiology (Impact Factor: 5.23). 07/2006; 163(11):1053-64. DOI: 10.1093/aje/kwj127
Source: PubMed


With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined.

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    • "Then we used a meta-analysis to pool the exposure-mortality effects among these subgroups. We further used a mixed-effects meta-regression model to investigate effect modification of community-level factors (Lin et al., 2013a; Smith-Warner et al., 2006). Spearman's correlation coefficients were calculated between the 13 community-level variables, and some variables were highly correlated (r N 0.9) (Supplementary Table A2). "
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    ABSTRACT: Many studies have reported increased mortality risk associated with heat waves. However, few have assessed the health impacts at a nation scale in a developing country. This study examines the mortality effects of heat waves in China and explores whether the effects are modified by individual-level and community-level characteristics. Daily mortality and meteorological variables from 66 Chinese communities were collected for the period 2006-2011. Heat waves were defined as ≥2 consecutive days with mean temperature ≥95th percentile of the year-round community-specific distribution. The community-specific mortality effects of heat waves were first estimated using a Distributed Lag Non-linear Model (DLNM), adjusting for potential confounders. To investigate effect modification by individual characteristics (age, gender, cause of death, education level or place of death), separate DLNM models were further fitted. Potential effect modification by community characteristics was examined using a meta-regression analysis. A total of 5.0% (95% confidence intervals (CI): 2.9%-7.2%) excess deaths were associated with heat waves in 66 Chinese communities, with the highest excess deaths in north China (6.0%, 95% CI: 1%-11.3%), followed by east China (5.2%, 95% CI: 0.4%-10.2%) and south China (4.5%, 95% CI: 1.4%-7.6%). Our results indicate that individual characteristics significantly modified heat waves effects in China, with greater effects on cardiovascular mortality, cerebrovascular mortality, respiratory mortality, the elderly, females, the population dying outside of a hospital and those with a higher education attainment. Heat wave mortality effects were also more pronounced for those living in urban cities or densely populated communities. Heat waves significantly increased mortality risk in China with apparent spatial heterogeneity, which was modified by some individual-level and community-level factors. Our findings suggest adaptation plans that target vulnerable populations in susceptible communities during heat wave events should be developed to reduce health risks. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Environment International 11/2014; 75C:103-109. DOI:10.1016/j.envint.2014.11.004 · 5.56 Impact Factor
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    • "First, we used multivariable logistic regression models to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) of the association between exposure and outcome in each study. Second, the study-specific ORs were pooled using random-effects meta-analysis to generate summary ORs [17]. We excluded study-specific results from a particular meta-analysis if the underlying model from that study failed to converge. "
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    ABSTRACT: Background Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. Methods Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. Results Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index. Conclusions This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.
    PLoS ONE 07/2014; 9(7):e103508. DOI:10.1371/journal.pone.0103508 · 3.23 Impact Factor
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    • "Missing data for the adjustment variables (<2.1% for each variable) were assigned to a separate category. Heterogeneity in the associations between marital status and first IHD events or IHD mortality by sub-groups of age, region and socio-economic, lifestyle and other factors, was assessed using a chi-squared contrast test [28]. "
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    ABSTRACT: Background: Being married has been associated with a lower mortality from ischemic heart disease (IHD) in men, but there is less evidence of an association for women, and it is unclear whether the associations with being married are similar for incident and for fatal IHD. We examined the relation between marital status and IHD incidence and mortality in the Million Women Study. Methods: A total of 734,626 women (mean age 60 years) without previous heart disease, stroke or cancer, were followed prospectively for hospital admissions and deaths. Adjusted relative risks (RRs) for IHD were calculated using Cox regression in women who were married or living with a partner versus women who were not. The role of 14 socio-economic, lifestyle and other potential confounding factors was investigated. Results: 81% of women reported being married or living with a partner and they were less likely to live in deprived areas, to smoke or be physically inactive, but had a higher alcohol intake than women who were not married or living with a partner. During 8.8 years of follow-up, 30,747 women had a first IHD event (hospital admission or death) and 2,148 died from IHD. Women who were married or living with a partner had a similar risk of a first IHD event as women who were not (RR = 0.99, 95% confidence interval (CI) 0.96 to 1.02), but a significantly lower risk of IHD mortality (RR = 0.72, 95% CI 0.66 to 0.80, P <0.0001). This lower risk of IHD death was evident both in women with and without a prior IHD hospital admission (respectively: RR = 0.72, 95% CI 0.60 to 0.85, P <0.0001, n = 683; and 0.70, 95% CI 0.62 to 0.78, P <0.0001, n = 1,465). These findings did not vary appreciably between women of different socio-economic groups or by lifestyle and other factors. Conclusions: After adjustment for socioeconomic, lifestyle and other factors, women who were married or living with a partner had a similar risk of developing IHD but a substantially lower IHD mortality compared to women who were not married or living with a partner.
    BMC Medicine 03/2014; 12(1-1):42. DOI:10.1186/1741-7015-12-42 · 7.25 Impact Factor
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