"Association between Folate and B12 Levels and Lung and Prostate Cancers." 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.
"Association Between S100 Proteins and Lung Cancer - A Pilot Study." Objective: The short-term goals of the pilot study are 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, which may help explain the effect of the intervention in the CARET study.
"Validation of Protein Markers for Lung Cancer Using CARET Sera and Proteomics Techniques." Objective: The objectives of this study are to (1) validate the finding from pilot studies with CARET sera of autoantibodies annexins I and II and PGP9.5 as potential biomarkers for lung cancers before the clinical diagnosis, evaluating sensitivity and specificity by time before diagnosis, treatment arm, gender, histologic type, and smoking status; (2) identify additional antigens and antibodies in sera from CARET participants, evaluating sensitivity and specificity by time before diagnosis, treatment arm, gender, histologic type, and smoking status, and, (3) compare the findings for individual biomarker candidates in participants who were current smokers versus former smokers.
"Analyzing CARET Specimens to Model Serum Markers for Cost Effective Ovarian Cancer Screening." Objective: The aim of this study was to provide serum samples from the CARET Serum Bank for seven female CARET participants previously diagnosed with ovarian cancer, and matched controls, in order to 1) pilot methods to conduct a case-control study of ovarian cancer serum markers for early detection, and 2) obtain preliminary estimates of the mean concentration and change in concentration over time in each marker and the correlation between markers, separately in cases and controls.
"Diet and Genetic Risks for Prostate Cancer." Objective: This proposal will investigate associations of dietary influences on oxidative balance (fat, fruit and vegetable intakes) and polymorphisms in oxidative stress regulatory enzymes with the risk of prostate cancer. The hypothesis is that dietary factors that increase oxidative stress (e.g., dietary fat) are associated with increased risk of prostate cancer; dietary factors that decrease oxidative stress (e.g., fruits and vegetables) are associated with decreased risk of prostate cancer; and the magnitude of these risks will vary by cancer susceptibility genetic profile. (Top of page)
"Diet and Genetic Risks for Prostate Cancer." Objective: This proposal will investigate associations of dietary influences on oxidative balance (fat, fruit and vegetable intakes) and polymorphisms in oxidative stress regulatory enzymes with the risk of prostate cancer. The hypothesis is that dietary factors that increase oxidative stress (e.g., dietary fat) are associated with increased risk of prostate cancer; dietary factors that decrease oxidative stress (e.g., fruits and vegetables) are associated with decreased risk of prostate cancer; and the magnitude of these risks will vary by cancer susceptibility genetic profile.
"SNPs and Cancer Risk and Response." Objective: This proposal will develop PCR arrays for a panel of 20 cytokine gene SNPs and apply the method to test a large clinical population of cancer patients and cancer-free individuals using samples from CARET. Investigators will collaborate with CARET and will genotype cytokine gene polymorphisms in genomic DNA that has been extracted from the archived blood spots, and will correlate the risk of cancer to each SNP using the cancer-free individuals as controls. We will investigate whether among cancer patients, the presence of certain SNPs correlates with survival. The specific aims of the study are to: 1) Develop and apply PCR arrays for genotyping SNPs in human genomic DNA; 1a) Design PCR arrays to detect SNPs encoded by cytokine genes; b) Define the extent and nature of CGPs in a clinical population of patients with lung cancer and in cancer-free individuals; 2) Define the frequency of CGPs in patients with lung cancer and in healthy individuals; 3) Determine the effect of CGPs on lung cancer survival.
"Pilot Study Genetic Association Study of Diabetes Candidate Genes and Pancreatic Cancer in the CARET Cohort." Objective: This proposal will investigate associations of single nucleotide polymorphisms (SNPs) and haplotypes in six diabetes candidate genes with risk for pancreatic cancer. DNA extraction from all samples will be completed in Year 1, using banked blood samples for all participants. Genotyping will be performed at the Functional Genomics Laboratory at the University of Washington with strict quality control procedures. Samples will be genotyped for half of the SNPs in Year 1, and the remaining SNPs will be genotyped in Year 2. Also in Year 2, haplotypes will be constructed using recently developed software, and both univariate and multivariate statistical approaches will be used to assess the genetic associations.
"Molecular Epidemiology of Lung Cancer." Objective: In a nested case-control study, this proposal is to determine whether polymorphisms of enzymes involved in the repair of smoking-induced DNA damage, namely those from the base excision (BER) and nucleotide excision repair (NER) pathways, are associated with risk of lung cancer. Genotyping of the functional single nucleotide polymorphisms (SNPs) as well as haplotype-tagging SNPs of 26 DNA repair genes, a total of 236 polymorphisms that have been resequenced by the Seattle Variation Discovery Resource for the Environmental Genome Project. The lung cancer cases (N = 900) and controls (n = 1800) for this study will come from the CARET specimen repository. Genotyping of cases and controls will utilize DNA obtained from leukocytes extracted from frozen whole blood samples. Detailed quantitative information on smoking and dietary history (using a food frequency questionnaire), obtained prior to the diagnosis of lung cancer, is available through CARET records. Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes, alone and in combination with other putative "high risk" genotypes within each pathway and in the two pathways combined. Results will be interpreted with multiple comparisons taken into account. The proposed study has sufficient statistical power to identify interactions between some of the high-risk genotypes, and to investigate whether the risk associated with a particular genotype varies by other risk factors, such as intake of antioxidant-rich fruits (e.g. Rosaceae fruits) and vegetables (e.g. Cruciferae vegetables), and food-derived nutrients, such as alpha-carotene, beta-carotene, lycopene, and tocopherols. (Top of page)
"Association of Supplemental Retinol and Bone Fractures." Objective:
"Association of Supplemental Beta-Carotene and Cataracts." Objective: (Top of page)
"Association Between S100 Proteins and Lung Cancer – A Pilot Study." Objective: The short-term goals of the pilot study are 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.
"SNPs in Lung Cancer Risk and Therapeutic Response." Objective: To utilize CARET specimens to refine experimental techniques for DNA extraction that will be used in a larger study of CARET specimens.
"Molecular Epidemiology of Lung Cancer." Objective: In a nested case-control study, this proposal is to determine whether polymorphisms of enzymes involved in the repair of smoking-induced DNA damage, namely those from the base excision (BER) and nucleotide excision repair (NER) pathways, are associated with risk of lung cancer. Genotyping of the functional single nucleotide polymorphisms (SNPs) as well as haplotype-tagging SNPs of 26 DNA repair genes, a total of 236 polymorphisms, that have been resequenced by the Seattle Variation Discovery Resource for the Environmental Genome Project. The lung cancer cases (N = 900) and controls (n = 1800) for this study will come from the CARET specimen repository. Genotyping of cases and controls will utilize DNA obtained from leukocytes extracted from frozen whole blood samples. Detailed quantitative information on smoking and dietary history (using a food frequency questionnaire), obtained prior to the diagnosis of lung cancer, is available through CARET records. Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes, alone and in combination with other putative "high risk" genotypes within each pathway and in the two pathways combined. Results will be interpreted with multiple comparisons taken into account. The proposed study has sufficient statistical power to identify interactions between some of the high-risk genotypes, and to investigate whether the risk associated with a particular genotype varies by other risk factors, such as intake of antioxidant-rich fruits (e.g. Rosaceae fruits) and vegetables (e.g. Cruciferae vegetables), and food-derived nutrients, such as alpha-carotene, beta-carotene, lycopene, and tocopherols. (Top of page)
"Predictors of Mesothelioma." Objective: To determine clinical predictors of mesothelioma by assessment of the following factors: occupational trade, cumulative asbestos exposure, parenchymal fibrosis, pleural plaques, and smoking history. (Top of page)