Epidemiology and Genomics Research Program

Bethesda, MD, United States

Epidemiology and Genomics Research Program

Bethesda, MD, United States
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Lee J.T.,U.S. National Institutes of Health | Lai G.Y.,U.S. National Institutes of Health | Liao L.M.,U.S. National Institutes of Health | Subar A.F.,U.S. National Institutes of Health | And 6 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2017

Background: Epidemiologic evidence on the association between nut consumption and lung cancer risk is limited. Methods: We investigated this relationship in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, a population-based case-control study, and the National Institutes of Health (NIH) American Association of Retired Persons (AARP) Diet and Health Study, a prospective cohort. We identified 2,098 lung cases for EAGLE and 18,533 incident cases in AARP. Diet was assessed by food frequency questionnaire for both studies. Multivariable ORs and HRs and respective 95% confidence intervals (CI) were calculated using unconditional logistic regression and Cox proportional hazards regression for EAGLE and AARP, respectively. Results: Higher frequency of intake of nut consumption was inversely associated with overall lung cancer risk (highest vs. lowest quintile, OREAGLE = 0.74; 95% CI, 0.57-0.95; HRAARP = 0.86; 95% CI, 0.81-0.91), regardless of smoking status. Results from the prospective cohort showed similar associations across histologic subtypes and a more pronounced benefits from nut consumption for those who smoked 1 to 20 cigarettes/day (OREAGLE = 0.61; 95% CI, 0.39-0.95; HRAARP = 0.83; 95% CI, 0.74-0.94). Conclusions: Nut consumption was inversely associated with lung cancer in two large population-based studies, and associations were independent of cigarette smoking and other known risk factors. Impact: To our knowledge, this is the first study that examined the association between nut consumption and lung cancer risk by histologic subtypes and smoking intensity. © 2017 American Association for Cancer Research.

PubMed | Epidemiology and Genomics Research Program, National Cancer Institute, University of Alberta, U.S. National Institute of Diabetes and Digestive and Kidney Diseases and 2 more.
Type: Journal Article | Journal: Advances in nutrition (Bethesda, Md.) | Year: 2014

The NIH has made a significant commitment through the NIH Common Funds Metabolomics Program to build infrastructure and capacity for metabolomics research, which should accelerate the field. Given this investment, it is the ideal time to start planning strategies to capitalize on the infrastructure being established. An obvious gap in the literature relates to the effective use of metabolomics in large-population studies. Although published reports from population-based studies are beginning to emerge, the number to date remains relatively small. Yet, there is great potential for using metabolomics in population-based studies to evaluate the effects of nutritional, pharmaceutical, and environmental exposures (the exposome); conduct risk assessments; predict disease development; and diagnose diseases. Currently, the majority of the metabolomics studies in human populations are in nutrition or nutrition-related fields. This symposium provided a timely venue to highlight the current state-of-science on the use of metabolomics in population-based research. This session provided a forum at which investigators with extensive experience in performing research within large initiatives, multi-investigator grants, and epidemiology consortia could stimulate discussion and ideas for population-based metabolomics research and, in turn, improve knowledge to help devise effective methods of health research.

Ioannidis J.P.A.,Epidemiology and Genomics Research Program | Ioannidis J.P.A.,Stanford University | Schully S.D.,Epidemiology and Genomics Research Program | Lam T.K.,Epidemiology and Genomics Research Program | And 2 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Knowledge integration includes knowledge management, synthesis, and translation processes. It aims to maximize the use of collected scientific information and accelerate translation of discoveries into individual and population health benefits. Accumulated evidence in cancer epidemiology constitutes a large share of the 2.7 million articles on cancer in PubMed. We examine the landscape of knowledge integration in cancer epidemiology. Past approaches have mostly used retrospective efforts of knowledge management and traditional systematic reviews and meta-analyses. Systematic searches identify 2,332 meta-analyses, about half of which are on genetics and epigenetics. Meta-analyses represent 1:89-1:1162 of published articles in various cancer subfields. Recently, there are more collaborative meta-analyses with individual-level data, including those with prospective collection of measurements [e.g., genotypes in genome-wide association studies (GWAS)]; this may help increase the reliability of inferences in the field. However, most meta-analyses are still done retrospectively with published information. There is also a flurry of candidate gene meta-analyses with spuriously prevalent "positive" results. Prospective design of large research agendas, registration of datasets, and public availability of data and analyses may improve our ability to identify knowledge gaps, maximize and accelerate translational progress or-at a minimum-recognize dead ends in a more timely fashion. ©2012 AACR.

Mahabir S.,Epidemiology and Genomics Research Program | Mahabir S.,NCI Inc | Baer D.J.,U.S. Department of Agriculture | Pfeiffer R.M.,NCI Inc | And 3 more authors.
European Journal of Clinical Nutrition | Year: 2014

The objective of this study was to evaluate the effect of 8 weeks of no alcohol, low (1 drink or 15 g/day) and moderate (2 drinks or 30 g/day) alcohol consumption on markers of bone health: fasting serum 25-hydroxy vitamin D (25(OH)D), osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), urine deoxypyridinoline (DPD) and helical peptide (HP) in postmenopausal women (n=51). Compared with no alcohol, 1 or 2 drinks/day for 8 weeks had no significant impact on any of the bone markers. Within each alcohol group, obese women had significantly lower serum 25(OH)D and higher DPD concentrations than normal weight women. Season significantly affected the concentrations of serum 25(OH)D, but there was no significant interaction between alcohol and season on serum 25(OH)D concentrations. Low or moderate alcohol consumption for 8 weeks had no significant impact on markers of bone health in postmenopausal women. © 2014 Macmillan Publishers Limited.

Hamilton J.G.,Sloan Kettering Cancer Center | Edwards H.M.,Frederick National Laboratory for Cancer Research | Khoury M.J.,Epidemiology and Genomics Research Program | Khoury M.J.,Centers for Disease Control and Prevention | Taplin S.H.,U.S. National Institutes of Health
Cancer Epidemiology Biomarkers and Prevention | Year: 2014

The long-standing medical tradition to "first do no harm" is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to disease. Genetic risk information can have varying implications for the health and well-being of patients and their relatives, and has raised important questions about the evaluation and value of risk information. This article explores the paradigms that are being applied to the evaluation of conventional cancer screening tests and emerging genetic and genomic tests of cancer susceptibility, and how these perspectives are shifting and evolving in response to advances in our ability to detect cancer risks. We consider several challenges germane to the evaluation of both categories of tests, including defining benefits and harms in terms of personal and clinical utility, addressing healthcare consumers' information preferences, and managing scientific uncertainty. We encourage research and dialogue aimed at developing a better understanding of the value of all risk information, nongenetic and genetic, to people's lives. Cancer Epidemiol Biomarkers Prev; 23(6); 909-16. ©2014 AACR.

Zanetti K.A.,U.S. National Cancer Institute | Zanetti K.A.,Epidemiology and Genomics Research Program | Haznadar M.,U.S. National Cancer Institute | Welsh J.A.,U.S. National Cancer Institute | And 10 more authors.
Cancer Research | Year: 2012

Because chronic intestinal inflammation is a risk factor for colorectal cancer, we hypothesized that genetic variants of inflammatory mediators, such as mannose-binding lectin 2 (MBL2), are associated with colon cancer susceptibility. Here, we report the association of 24 MBL2 single-nucleotide polymorphisms (SNP) and corresponding haplotypes with colon cancer risk in a case-control study. Four SNPs in the 3′-untranslated region (UTR) of the gene (rs10082466, rs2120132, rs2099902, and rs10450310) were associated with an increased risk of colon cancer in African Americans. ORs for homozygous variants versus wild-type ranged from 3.17 [95% confidence interval (CI), 1.57-6.40] to 4.51 (95% CI, 1.94-10.50), whereas the 3′-UTR region haplotype consisting of these four variants had an OR of 2.10 (95% CI, 1.42-3.12). The C allele of rs10082466 exhibited a binding affinity of miR-27a and this allele was associated with both lower MBL plasma levels and activity. We found that 50 secretor haplotypes known to correlate with moderate and low MBL serum levels exhibited associations with increased risk of colon cancer in African Americans, specifically as driven by two haplotypes, LYPA and LYQC, relative to the referent HYPA haplotype (LYPA: OR, 2.60; 95% CI, 1.33-5.08 and LYQC: OR, 2.28; 95% CI, 1.20-4.30). Similar associations were not observed in Caucasians. Together, our results support the hypothesis that genetic variations in MBL2 increase colon cancer susceptibility in African Americans. ©2012 AACR.

Lynch J.A.,Dana-Farber Cancer Institute | Lynch J.A.,Center for Health Quality | Khoury M.J.,Epidemiology and Genomics Research Program | Borzecki A.,Center for Health Quality | And 6 more authors.
Genetics in Medicine | Year: 2013

Purpose: We examined hospital use of the epidermal growth factor receptor assay in patients with lung cancer in the United States. Our goal was to inform the development of a model to predict phase 3 translation of guideline-directed molecular diagnostic tests. Methods: This was a retrospective observational study. Using logistic regression, we analyzed the association between hospitals' institutional and regional characteristics and the likelihood that an epidermal growth factor receptor assay would be ordered. Results: Significant institutional predictors included affiliation with an academic medical center (odds ratio, 1.48; 95% confidence interval, 1.20-1.83), participation in a National Cancer Institute clinical research cooperative group (odds ratio, 2.06, 1.66-2.55), and availability of positron emission tomography scan (odds ratio, 1.44, 1.07-1.94) and cardiothoracic surgery (odds ratio, 1.90, 1.52-2.37) services. Significant regional predictors included metropolitan county (odds ratio, 2.08, 1.48-2.91), population with above-average education (odds ratio, 1.46, 1.09-1.96), and population with above-average income (odds ratio, 1.46, 1.04-2.05). Distance from a National Cancer Institute cancer center was a negative predictor (odds ratio, 0.996, 0.995-0.998), with a 34% decrease in likelihood for every 100 miles. Conclusion: In 2010, only 12% of US acute-care hospitals ordered the epidermal growth factor receptor assay, suggesting that most patients with lung cancer did not have access to this test. This case study illustrated the need for: (i) increased dissemination and implementation research, and (ii) interventions to improve adoption of guideline-directed molecular diagnostic tests by community hospitals. © American College of Medical Genetics and Genomics.

Ghazarian A.A.,Epidemiology and Genomics Research Program | Ghazarian A.A.,U.S. National Cancer Institute | Simonds N.I.,Epidemiology and Genomics Research Program | Bennett K.,Epidemiology and Genomics Research Program | And 6 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Background: Genetic and environmental factors jointly influence cancer risk. TheNIHhas made the study of gene-environment (GxE) interactions a research priority since the year 2000. Methods: To assess the current status of GxE research in cancer, we analyzed the extramural grant portfolio of the National Cancer Institute (NCI) from Fiscal Years 2007 to 2009. Publications attributed to selected grants were also evaluated. Results: From the 1,106 research grants identified in our portfolio analysis, a random sample of 450 grants (40%) was selected for data abstraction; of these, 147 (33%) were considered relevant. The most common cancer type was breast (20%, n 29), followed by lymphoproliferative (10%, n 14), colorectal (9%, n 13), melanoma/other skin (9%, n 13), and lung/upper aerodigestive tract (8%, n 12) cancers. The majority of grants were studies of candidate genes (68%, n 100) compared with genome-wide association studies (GWAS) (8%, n 12). Approximately one-third studied environmental exposures categorized as energy balance (37%, n 54) or drugs/treatment (29%, n 43). From the 147 relevant grants, 108 publications classified as GxE or pharmacogenomic were identified. These publications were linked to 37 of the 147 grant applications (25%). Conclusion: The findings from our portfolio analysis suggest that GxE studies are concentrated in specific areas. There is room for investments in other aspects of GxE research, including, but not limited to developing alternative approaches to exposure assessment, broadening the spectrum of cancer types investigated, and conducting GxE within GWAS. Impact: This portfolio analysis provides a cross-sectional review of NCI support for GxE research in cancer. © 2013 American Association for Cancer Research.

Lam T.K.,U.S. National Cancer Institute | Lam T.K.,Epidemiology and Genomics Research Program | Freedman N.D.,Nutritional Epidemiology Branch | Fan J.-H.,Peking Union Medical College | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2013

Background: China has some of the highest incidence rates for gastric adenocarcinoma (GA) and esophageal squamous cell carcinoma (ESCC) in the world. Prospective studies suggested that vitamin C may reduce risks; however, associations are unclear because of limited sample size. Objective: The objective was to examine the relation between prediagnostic plasma vitamin C and the risk of GA and ESCC. Design: A case-cohort study was used to assess the association between prediagnostic plasma vitamin C and incidence of GA (n = 467) and ESCC (n = 618) in the General Population Nutrition Intervention Trial. With the use of multivariate Cox proportional hazards models, we estimated the HRs and 95% CIs. We also conducted a meta-analysis of the literature up to 1 October 2012 on the relation between circulating vitamin C and gastric cancer incidence. Two cohort studies and the current study were included to assess the body of evidence. Results: For GA, each 20-μmol/L increase in plasma vitamin C was associated with a 14% decrease in risk (HR: 0.86; 95% CI: 0.76, 0.96). Compared with individuals with low plasma vitamin C concentrations (≤28 μmol/L), those with normal concentrations (>28 μmol/L) had a 27% reduced risk of GA (HR: 0.73; 95% CI: 0.56, 0.94). No association between vitamin C concentrations and ESCC was seen. Meta-analysis showed that the risk of incident GA among those with the highest concentration of plasma vitamin C was 31% lower (random-effects-pooled-odds ratio 0.69; 95% CI: 0.54, 0.89) than those in the lowest category. Conclusion: Our data provide evidence that higher circulating vitamin C was associated with a reduced risk of incident GA, but no association was seen for ESCC. © 2013 American Society for Nutrition.

Peng B.,University of Houston | Chen H.-S.,U.S. National Institutes of Health | Mechanic L.E.,Epidemiology and Genomics Research Program | Racine B.,Cornerstone Systems Northwest Inc. | And 4 more authors.
Bioinformatics | Year: 2013

Many simulation methods and programs have been developed to simulate genetic data of the human genome. These data have been widely used, for example, to predict properties of populations retrospectively or prospectively according to mathematically intractable genetic models, and to assist the validation, statistical inference and power analysis of a variety of statistical models. However, owing to the differences in type of genetic data of interest, simulation methods, evolutionary features, input and output formats, terminologies and assumptions for different applications, choosing the right tool for a particular study can be a resource-intensive process that usually involves searching, downloading and testing many different simulation programs. Genetic Simulation Resources (GSR) is a website provided by the National Cancer Institute (NCI) that aims to help researchers compare and choose the appropriate simulation tools for their studies. This website allows authors of simulation software to register their applications and describe them with well-defined attributes, thus allowing site users to search and compare simulators according to specified features. © 2013 The Author.

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