Pilot and Unpublished Studies

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Disease  |  Types of Study

Disease

Title: Replication genotyping for selected SNPs in relation to serum beta-carotene, retinol, and alpha-tocopherol and lung cancer risk
Investigator: Albanes, Demetrius
Institution: National Cancer Institute Division of Cancer Epidemiology and Genetics
Objective: To replicate an association between candidate SNPs and 1) follow-up serum concentrations of beta-carotene, retinol,and alpha-tocopheral by CARET intervention arm and 2) lung cancer risk by CARET intervention arm.

Title: Detecting early stage lung cancer with antibodies
Investigator: Bihain, Bernard
Institution: Genclis
Objective: Pilot study to validate the feasibility of detecting changes in antibodies directed against bioinformatically predicted aberrant peptides in samples from patients of CARET study diagnosed with lung cancer versus controls without cancer after five-year follow-up.

Title: Evaluation of soluble MICA as a biomarker for lung cancer
Investigator: Chien, Jason
Institution: Fred Hutchinson Cancer Research Center
Objective: To determine whether soluble MICA can be detected in CARET serum samples.

Title: EGFR pathway & lung cancer risk: haplotype analysis ILCCO
Investigator: Chen, Chu
Institution: Fred Hutchinson Cancer Research Center Public Health Sciences
Objective: To identify and determine whether certain haplotypes of the EGFR and of downstream signalling molecules are associated with the development of lung cancer.

Title: Evaluation of Pro-Gastrin Releasing Peptide (ProGRP) in Small Cell Lung Cancer
Investigator: Dowell, Barry
Institution: Abbott Diagnostics
Objective: To determine whether pro-GRP is elevated prior to the clinical detection of small cell lung cancer using a case-control study design, and compare serum versus plasma results in a small subset of samples.

Title: Effect of CARET Intervention on Pro-Gastrin Releasing Peptide in Small Cell Lung Cancer
Investigator: Dowell, Barry
Institution: Abbott Diagnostics
Objective: To determine if beta carotene and retinol supplementation increases plasma concentrations of pro-gastrin releasing peptide (ProGRP) in 55 cancer-free participants in the placebo group and 55 participants on the active intervention, as an initial step in exploring the hypothesis that the mechanism of the adverse effect of beta carotene and retinol on lung cancer incidence may be through an increased plasma concentration of Pro-GRP/GRP.

Title: Associations Between Genetic Factors and Risk of Lung Cancer and Other Diseases
Investigator: Goodman, Gary
Institution: Fred Hutchinson Cancer Research Center Public Health Sciences
Objective: To determine possible associations between genetic factors and risk of lung cancer and other diseases. Existing participant samples from CARET serum bank will be sent to collaborating laboratories for analysis.

Title: Pilot Study of S100 Proteins as Cancer Biomarkers Using CARET Sera
Investigator: Hanash, Samir
Institution: University of Michigan
Objective: Pilot study with the short-term goal to test for S100 proteins (MRP8 and MRP14) in stored CARET serum. The long-term goals of this research are to investigate whether these biomarkers are correlated with disease and may help explain the effect of the intervention in the CARET study.

Title: Antibodies to the HE4 protein and development of lung adenocarcinoma
Investigator: Hellstrom, Ingegerd
Institution: University of Washington
Objective: To investigate a possible relationship between antibodies to HE4 and tumor development, a study is proposed in the Hellstrom laboratory to evaluate coded serum samples from healthy male and female donors who later developed lung adenocarcinoma. This tumor type was chosen because most lung adenocarcinomas express HE4 according to immunohistology and the HE4 protein can be detected in serum while many squamous cell lung carcinomas do not express HE4. If antibodies are found more frequently in this group than in controls we may later consider to also measure antibodies to mesothelin which is overexpressed in lung adenocarcinomas but will not include mesothelin in the pilot study. If the pilot study supports a larger investigation we may in that case also measure antigen in the serum samples.

Title: Association between Folate and B12 Levels and Lung and Prostate Cancers
Investigator: King, Irena
Institution: Fred Hutchinson Cancer Research Center Public Health Sciences
Objective: To investigate the relationship between serum folate and B12 levels and lung and prostate cancer incidence in CARET participants. To determine the effect of intervention on the serum folate and B12 levels in CARET participants with and without the diagnoses of lung and prostate cancers.

Title: Role of BRM Loss in Tumor Development in the CARET Trial
Investigator: Reisman, David
Institution: University of Florida Health
Objective: 1) To determine if there is a greater frequency of BRM and/or BRG1 loss in tumors from the retinoid-treated patients compared with the placebo group. Perform immunohistochemical (IHC) staining to evaluate the BRM and BRG1 status of available tumor slides derived from lung cancers in this trial. 2) To determine if BRM polymorphisms are statistically enriched in retinoid-treated patients compared with placebo-control patients. Calculate odds ratios to determine if there is a statistically significant increase in the frequency of BRM polymorphisms in the cases. Explore whether there exists differences in the association between BRM polymorphisms and cancer risk in the retinoid-treated participants, as compared to the placebo-treated, both through subset analyses (by treatment arm), and in a treatment arm-polymorphism interaction analysis. 3) To determine whether there is a statistically significant association between HIS staining and BRM polymorphisms in this set of patients from the CARET trial; perform logistic regression.

Title: Detection of Aberrant Hypermethylation of Cancer-Related Genes in Serum as a Screening Tool for Early Detection of Lung Cancer
Investigator: Sidransky, David
Institution: Johns Hopkins Medicine
Objective: Pilot study to validate ability to use CARET samples to confirm the possibility of performing a study looking at aberrant promoter hypermethylation of cancer related genes (p16, MGMT, DAP-kinase, GSTP1, and APC) in serum/plasma samples as tool for the early detection of lung cancer in high-risk populations and/or monitoring patients with lung cancer during treatment utilizing CARET specimens.

Title: Development and validation of lung cancer risk prediction models
Investigator: Tammemagi, Martin
Institution: Brock University Applied Health Sciences
Objective: 1. In CARET data, to externally validate existing lung cancer risk prediction models in their ability to predict incident lung cancers, and lung cancer mortality. Almost all of the currently published models have been designed to identify becoming a lung cancer case. But some recent discussion regarding selection criteria for screening has suggested identification of those who will die from lung cancer may also be relevant. 2. To validate the Tammemagi 2012 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) model into which asbestos has been synthetically added as predictors. And if found to be deficient use CARET data to improve the parameter estimates for asbestos in the Tammemagi 2012 model. 3. To develop and validate lung cancer risk prediction models for never-smokers (if data permits).

Title: Prevalence of Anti-P53 antibodies and P53 Mutations in CARET Participants with Lung or Prostate Cancer.
Investigator: Trivers, Glen
Institution: National Cancer Institute Human Carcinogenesis
Objective: To determine the incidence of measurable concentrations of antibodies against the mutant P53 protein in CARET participants with and without lung cancer.

Title: Association between Growth Factors and Risk of Lung Cancer and Other Diseases
Investigator: Williams, James
Institution: University of California Irvine Department of Medicine
Objective: To determine in the CARET population if particular growth factors are associated with the incidence of lung cancer and cardiovascular disease.

Title: Antibodies to HE4 and mesothelin predictive for future ovarian cancer
Investigator: Hellstrom, Ingegerd
Institution: University of Washington
Objective: To investigate whether antibodies to two biomarkers, mesothelin and HE4, are related to the development of ovarian carcinoma (OvC) by being more frequently detected in sera from symptom-free women who later developed OvC cancer than in sera from women who did not.

Title: Serum Test for Preclinical Detection of Ovarian Cancer
Investigator: Lokshin, Anna
Institution: University of Pittsburgh Department of Medicine
Objective: To test the hypothesis that to develop an effective screening algorithm for identification of preclinical (pre-diagnostic) ovarian cancer, algorithm training should be performed on samples collected prior to diagnosis. Our primary objectives are to develop and validate reliable and highly sensitive multimarker assays for early (preclinical) detection and diagnosis of ovarian cancer.

Title: Detection of Epithelial Ovarian Cancer in CARET study using H-NMR metabonomics
Investigator: Odunsi, Kunle
Institution: Roswell Park Cancer Institute Gynecologic Oncology
Objective: To validate 1H-NMR based on metabonomics for early detection utilizing samples from the Carotene and Retinol Efficacy Trial (CARET) study. The primary goal is to evaluate, as a function of time before clinical diagnosis, the capacity of metabonomics to detect preclinical disease. Specimens obtained within 3 years of the closet time point to diagnosis from ovarian cancer cases will be tested utilizing NMR metabonomics.

Title: miRNA Biomarkers for Early Ovarian Cancer Detection
Investigator: Tewari, Maneesh
Institution: Fred Hutchinson Cancer Research Center Human Biology
Objective: To assess performance of miR-135b as a single biomarker in pre-clinical samples from the Carotene and Retinol Efficacy Trial (CARET) repository. Secondary analyses will include sensitivity using the PEB longitudinal algorithm, sensitivity at other levels of specificity, contribution to a decision rule including CA125, HE4, and Mesothelin and evaluation of miR-135b in a risk algorithm.

Title: Auto-antibodies to p53 for Early Ovarian Cancer Detection
Investigator: Urban, Nicole
Institution: Fred Hutchinson Cancer Research Center Public Health Sciences
Objective: To test the hypothesis that addition of the p53 autoantibody assay to CA125, HE4, and mesothelin will enhance the ability to detect ovarian cancer in its early, curable stage.

Title: Association between Folate and B12 Levels and Lung and Prostate Cancers
Investigator: King, Irena
Institution: Fred Hutchinson Cancer Research Center Public Health Sciences
Objective: To investigate the relationship between serum folate and B12 levels and lung and prostate cancer incidence in CARET participants. To determine the effect of intervention on the serum folate and B12 levels in CARET participants with and without the diagnoses of lung and prostate cancers.

Title: SNPs in Cancer Risk and Response
Investigator: Petersdorf, Effie
Institution: Fred Hutchinson Cancer Research Center Clinical Research
Objective: To determine the clinical significance of SNPs in immune respone genes in patients diagnosed with cancer. SNPs will be genotyped using PCR-based platforms. We will define the extent and nature of SNPs in a clinical population of patients with cancer cancer (all types excluding non-melanoma skin cancer) and in cancer-free individuals (controls). The frequency of SNPs in the cases and controls will be determined in order to assess the effect of SNPs on cancer survival and response to therapy.

Title: Serum Concentrations of Mesothelin in the Early Diagnosis of Mesothelioma
Investigator: Hellstrom, Ingegerd
Institution: Pacific Northwest Research Institute
Objective: Pilot study to determine if mesothelin is elevated in patients with malignant mesothelioma. An initial phase II trial has been added to measure the concentration of MPF/Mesothelin in the serum of 10 patients with a diagnosis of malignant mesothelioma and 10 matched healthy controls.

Title: Genome-Wide Association Study of Fibrosing Interstitial Lung Diseases
Investigator: Schwartz, David
Institution: University of Colorado Denver School of Medicine
Objective: To discover genes and gene variants that are central to the development of fibrosing interstitial lung diseases.

Title: Is there an Association between Glutathione -S-transferase M1 Deletion and the Severity of Asbestos-Related Lung Disease
Investigator: Thornquist, Mark
Institution: Fred Hutchinson Cancer Research Center Public Health Sciences
Objective: To determine if Glutathione S-transferases Mu1 gene deletion is a risk factor for asbestos related fibrosis in this subset of the CARET population.

Title: Association Between Serum Homocysteine and Folate Levels and Cardiovascular Disease
Investigator: Omenn, Gilbert
Institution: University of Michigan School of Public Health
Objective: To investigate associations and relative risks for the folic acid-homocysteine-cardiovascular disease endpoints cascade in CARET participants, testing whether low folic acid generation and ingestion correlate with serum folate levels; serum folate with serum total homocysteine levels; and the relationship between homocysteine levels and cardiovascular disease and coronary heart disease.

Title: Association between Growth Factors and Risk of Lung Cancer and Other Diseases
Investigator: Williams, James
Institution: University of California Irvine Department of Medicine
Objective: To determine in the CARET population if particular growth factors are associated with the incidence of lung cancer and cardiovascular disease.

Title: Biomarkers for Early Detection of Mesothelioma
Investigator: Carbone, Michele
Institution: University of Hawaii Cancer Center
Objective: To evaluate HMGB1 as 1) a diagnostic marker which can distinguish MM from lung cancer, and 2) as a biomarker of mineral fiber exposure and a possible marker of MM, determine whether different fiber types elicit similar increases on HMGB1 in the serum, and whether treatment with aspirin modulates HMGB1 in the sera of an asbestos-exposed cohort from a prospective, double-blind, double cross-over study.

Title: Serum Concentrations of Mesothelin in the Early Diagnosis of Mesothelioma
Investigator: Hellstrom, Ingegerd
Institution: Pacific Northwest Research Institute
Objective: Pilot study to determine if mesothelin is elevated in patients with malignant mesothelioma. An initial phase II trial has been added to measure the concentration of MPF/Mesothelin in the serum of 10 patients with a diagnosis of malignant mesothelioma and 10 matched healthy controls.

Title: Soluble Mesothelin Related Peptide (SMRP) and Osteopontin (OPN) as Early Detection Markers for Malignant Mesothelioma (MM)
Investigator: Pass, Harvey
Institution: New York University Medical Center
Objective: To determine whether SMRP and OPN are specific and sensitive biomarkers for malignant mesothelioma (MM), and whether a rise in the level of either or both markers in a high risk asbestos exposed cohort of patients will occur prior to the development of clinically apparent mesothelioma.

Types of Study

Title: Association between Folate and B12 Levels and Lung and Prostate Cancers
Investigator: King, Irena
Institution: Fred Hutchinson Cancer Research Center Public Health Sciences
Objective: To investigate the relationship between serum folate and B12 levels and lung and prostate cancer incidence in CARET participants. To determine the effect of intervention on the serum folate and B12 levels in CARET participants with and without the diagnoses of lung and prostate cancers.

Title: Hepatoxicity-Hepatic Effects of Low Dose Vitamin A Supplementation
Investigator: Brodkin, Carl
Institution: Harborview Medical Center
Objective: To assess the technical feasibility of quantitatively determining procollagen levels from frozen banked serum on 10 participants from the CARET intervention group and compare them to 10 participants from the CARET placebo group. The specific aims of this data was to provide an estimate of mean values, variance, and distribution to utilize in sample size calculations for a larger, comprehensive study.

Title: Determining the Plasma Disappearance and Pharmakokinetics of Beta-Carotene and Long Term Oral Supplementation
Investigator: Redlich, Carrie
Institution: Yale University School of Medicine
Objective: To determine the serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol over time after CARET participants discontinued oral supplementation with beta-carotene. This study began at the time the CARET intervention ended.

Title: Determining the Plasma Disappearance and Pharmakokinetics of Beta-Carotene after Long-Term Oral Supplementation
Investigator: Redlich, Carrie
Institution: Yale University School of Medicine
Objective: To determine the effects of long-term supplementation of Beta-carotene and retinyl palmitate on lipoptroteins (HDL, LDL, VLDL) and other carotenoids and retinoids by analysis of existing serum samples on 52 New Haven CARET participants stored at the CARET Coordinating Center. These results will be compared to existing chart data on CARET Seattle participants.

Title: Immunization-Vitamin Enhancement in Pneumococcal Vaccine Response
Investigator: Williams, James
Institution: University of California Department of Medicine
Objective: To examine the effects of the combination of beta-carotene and retinyl palmitate on antibody responses to immunization for Streptococcus Pneumoniae and influenza infections among CARET participants.