More information and a full updated listing of projects can be found on the Vanderbilt Epidemiology Center website.

COHORT STUDIES

The Southern Community Cohort Study (SCCS, R01 CA092447, PI: Blot) was launched in 2002 as one of the largest and most intensive studies ever to evaluate the determinants of cancer among African Americans and among low income adults regardless of race. Approximately 86,000 men and women aged 40-79 years, 2/3 of whom are African American, across 12 southern states (TN, KY, AR, LA, MS, AL, FL, GA, SC, NC, VA, and WV) have been enrolled in the SCCS, most (85%) from community health centers (CHCs) primarily serving America’s uninsured. Extensive baseline questionnaire data have been obtained, and biologic specimens (blood, urine, and/or buccal cells) have been collected and stored at VU for approximately 90% of participants. A series of studies are being carried out to evaluate whether 1) energy balance (physical inactivity and adiposity), 2) vitamin D, 3) inflammation, 4) selenium and other dietary factors, 5) tobacco carcinogen metabolism, 6) cancer screening practices, 7) survivorship, quality of life and function, and 8) genetic polymorphisms are associated with major cancers (prostate, breast, lung, and colorectal) among African Americans and whether they are the underlying reasons for cancer disparities. Other research activities in the SCCS include H. pylori eradication, nutrition and gastric cancer prevention; metformin use and breast cancer risk; inflammatory biomarkers and lung cancer; and colonoscopy screening among African Americans. The SCCS contributes to multiple consortium projects and has spawned more than 130 publications,This cohort provides an unparalleled opportunity and resources for MAGEC trainees to develop skills and a career in cancer epidemiology, particularly in cancer disparities. 

The Shanghai Women's Health Study (SWHS, R37 CA70867, PI: Zheng) is a population-based prospective cohort study initiated in 1996. From 1996 to 2000, approximately 75,000 Chinese women living in Shanghai were recruited into the study. In addition to survey data, most study participants donated blood (75%) and urine (87%) samples at baseline. This cohort of women is being followed for the occurrence of cancer and several common diseases and mortality through a combination of biennial home visits and record linkages with files routinely collected by the Shanghai Cancer Registry and Vital Statistical Unit. In the current funding cycle, the study is focusing on evaluating dietary factors and biomarkers for cancer. The resources from this study have supported approximately 40 ongoing or planned studies to address etiologic hypotheses for cancers and other chronic diseases, such as coronary heart disease, asthma, diabetes, stroke, hypertension, and bone fracture. To date, over 320 research papers have been published using data and biological samples collected in the SWHS. In 2009, Dr. Zheng received a MERIT award from NCI to support this large cohort study for up to 10 years. The SWHS provides exceptional opportunities for trainees to develop skills in conducting large cohort studies in nutritional and molecular epidemiology of chronic diseases.

The Shanghai Men’s Health Study (SMHS, R01 CA82729, PI: Shu) is a population-based cohort study of 61,582 men that is being conducted in parallel with the SWHS using similar study protocols. Study recruitment took placed between 2001 and 2006. In addition to survey data, 75% of study participants provided a blood sample, nearly 90% provided a urine sample, and 22% a buccal cell sample. Two food frequency questionnaires were/are being administered in person two years apart. The cohort is being followed through a combination of biennial home visits of all living subjects and record linkages to collect information on mortality, occurrence of cancer and major chronic diseases, including diabetes, hypertension cardiovascular disease, and bone fracture. The cohort has been followed up for cancer occurrence and deaths via linkage with the population-based Shanghai Cancer Registry and the Shanghai Vital Statistics Unit, as well as through visits to all living cohort members every 3-4 years. The SMHS has contributed to over 20 consortium studies, and more than 140 publications. The SWHS and SMHS, with their large sample size, wealth of resources, and unique exposure patterns and disease spectrum, provide exceptional opportunities for MAGEC trainees to address significant hypotheses that cannot be adequately investigated in other existing cohorts. 

 

GENETIC EPIDEMIOLOGICAL STUDIES

Breast Cancer Genetic Study in African-Ancestry (AA) Populations (R01CA202981, PIs: Zheng, Haiman, and Palmer) is a large consortium study in African-ancestry women including approximately 20,000 breast cancer patients and an equal number of controls to systematically search the whole genome using a next-generation sequencing approach to discover novel genetic susceptibility factors for breast cancer for AA women. This study will also build a comprehensive reference panel for imputation and meta-analysis of GWAS data, and use gene expression signatures to understand the mechanism underlying the influence of germline variants on breast cancer biology. This study will generate critically needed data to improve understanding of the genetics, biology, and etiology of breast cancer in AAs.

The Genome Sequencing to Identify Novel Genetic Factors for Breast Cancer Risk study (R01CA158473, PI: Zheng), builds upon the resources established in three NCI-funded large epidemiologic studies conducted among women in Shanghai, and aims to systematically search the entire coding region in the human genome to identify new genetic susceptibility factors for breast cancer.

Colorectal Cancer Risk Loci: GWAS, Fine-Mapping, and Functional Analysis (R01CA188214, PIs: Zheng and Long) is the first large study in East Asians, involving 48,800 participants, to comprehensively search for genetic risk factors for CRC. The study will also employ experimental approaches to identify functional variants and novel genes/pathways through which GWAS-identified loci contribute to CRC risk.

Translating Gene-Calcium Interactions to Precision Medicine for Colorectal Cancer (1U01CA182364-01, PIs: Dai, Edwards) aims to unravel functional variants and identify new rare variants using a next-generation sequencing approach and then prospectively evaluate if calcium-gene interactions affect colon carcinogenesis (incidence adenoma, recurrent adenoma and incident cancer), and discover the underlying mechanism(s) for these interactions. This study uses PLCO resources.

The Design and Analysis of Sequencing Studies for Gene Mapping in Families project (R01HG006857, PI: Li) is designed to develop novel statistical and computational methods to address the challenges of identification of rare variants associated with complex traits for family studies.

Exome Sequencing to Identify Novel Genetic Factors for Lung Cancer in Nonsmokers (U01CA161045, PI: Cai) is a whole-exome sequencing study to systematically search the entire coding region in the human genome for lung cancer susceptibility genes and variants among never-smokers. The study will sequence the whole exome of 600 lung cancer cases and 600 controls and validate variants/genes in two independent samples of 2500 cases and 2500 controls.

The Analysis, Validation and Resource Creation for Genome Sequencing of Complex Diseases project (U01HG009086, PIs: Li and Cox) is one of the Analysis Centers funded by NHGRI for the Genome Sequencing Program, which is carrying out high depth-whole genome sequencing for a variety of complex diseases. The study will develop and apply novel approaches for prioritizing results using BioVU, the 200,000 member biobank at Vanderbilt with high quality electronic health records. Queriable results databases are being developed for use by both the internal sequencing community and the broader scientific community.

The multi-stage Genome-Wide Association Study (GWAS) Analysis of Uterine Fibroid Tumors (R01HD074711, PI: Velez Edwards) aims to identify genetic markers for risk of fibroids through a GWAS of AA and European American participants. The study uses BioVU and data obtained from the cohorts participating in the Electronic MEdical Records and GEnomic network (eMERGE).

The Searching For New Risk Variants In Known Breast Cancer Risk Loci In Asians study (R03CA176757, PI: Long) aims to identify novel genetic variants and independent genetic signals in previously-identified GWAS loci in Asian ancestry populations. The GWAS data of ~9,400 breast cancer cases and controls of Asian ancestry will be imputed using the 1,000 Genomes Project data as reference to evaluate 10 breast cancer loci in which the index SNPs were not replicated in Asians.

The Unraveling Genetic Determinants of Lung Cancer Risk in African Americans study (K07CA172294, PI Aldrich) seeks to identify genetic factors contributing to lung cancer in African Americans by sequencing the exomes of lung cancer cases and controls, and to identify interactions between local African ancestry and smoking exposure on lung cancer.

 

MOLECULAR EPIDEMIOLOGICAL STUDIES

Sex Hormones, Phytoestrogens, and Lung Cancer in Female Nonsmokers is a case-control study of lung cancer (R01CA200999, PI: Yang) nested in the SWHS to investigate the role of endogenous and plant estrogens (phytoestrogens) on lung cancer risk and mortality among female never smokers (N=600 pairs). 

A Prospective Analysis of Obesity and Progression from HGPIN to Prostate Cancer (American Institute of Cancer Research, PI: Fowke) creates a cohort of 250 men with high-grade prostatic intraepithelial neoplasia and follows them for conversion to prostate cancer.  Blood and urinary markers of inflammation will be measured to identify the role of inflammation in the early phases of prostate carcinogenesis. 

The Magnesium and Racial Disparities in Prostate Cancer Detection and Prognosis study (PC141010, Department of Defense, PI: Fowke) investigates the link between dietary and blood magnesium levels with prostate cancer diagnosis and prognosis following treatment among African American and white men and the link between blood magnesium and prostate tissue inflammation.

The Effect of Magnesium Treatment on Vitamin D Resistance study (R03CA189455, PI: Shrubsole) aims to evaluate the effect of magnesium supplementation on circulating biomarkers of vitamin D status in the context of a randomized controlled trial.

The Methionine Metabolism in Esophageal Adenocarcinoma Carcinogenesis study (R03CA19566, PI: Shrubsole) is a case-control study to test the hypothesis that a high S- adenosylmethionine level is associated with a reduced risk of Barrett’s esophagus, esophageal adenocarcinoma.

The Tennessee Colorectal Polyp Study (TCPS, P50CA095103, Project leader Zheng) is a major project in the Vanderbilt SPORE in GI Cancer (P50CA095103, PI Coffey) aiming to evaluate lifestyle factors and biomarkers for colorectal polyps. More than 6,000 patients were recruited, completed a telephone interview, and provided various biological samples, including blood, exfoliated buccal cells, polyp tissues, and tissues from rectal biopsies. The resources from this project have supported multiple externally-funded studies, including three K07 grants for career development of junior investigators. In the current funding period, the primary goal of the study is to identify biomarkers to predict the risk of adenoma recurrence. 

 

MICROBIOME STUDIES

The Oral Microbiome and Lung Cancer Risk study (R01CA207466, PIs: Cai and Rosenberg) investigates whether the oral microbiome may be associated with lung cancer risk among 1800 AAs and European Americans, and if so, whether the association differs between these two racial groups.

Foregut Microbiome, Gastric Intestinal Metaplasia, and Gastric Cancer Risk (R01 CA204113, PIs: Chen/Shu/Pei) applies a metagenome approach to systematically investigate the role of foregut microbiota in the development of gastric cancer, using resources collected in the SWHS, SMHS, SCCS and a clinic-based case-control study of gastric intestinal metaplasia. Promising findings will be validated by evaluating antibodies to specific microbiota.  A total of 900 gastric cancer cases, 120 gastric intestinal metaplasia cases, and 1440 controls will be included in the study.

A Prospective Investigation of the Oral Microbiome and Pancreatic Cancer (U01 CA187508, PIs: Palm/Shu) is a nested case-control study of 475 cases and controls to investigate whether oral microbiota are associated with the development of pancreatic cancer among African Americans, applying metagenome analysis of oral microbiota in pre-diagnosis mouthwash samples.

Reproducibility and Validity of Microbiomial Markers in Colorectal Cancer (R03CA183019, PI: Shrubsole) is a study in which 16S rRNA and metagenomic analyses of gut microbiome samples is being conducted. The purpose of the study is to evaluate similarities and differences according to microbiome niche and to further understand the relationship of the niches to carcinogenesis biomarkers in rectal tissue.

The Ca2+/Mg2+ Balance, Microbiota, Necroptosis & Inflammation study (R01DK110166, PIs: Dai, Shrubsole) investigates the influence of calcium and magnesium ratio and gut microbiota on necroptosis and inflammation biomarkers. 

 

CLINICAL TRIALS AND INTERVENTION STUDIES

The Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Prevention study (NCI, PI: Dai) will evaluate if 3-week on/3-week off aspirin use in individuals at average risk of colorectal cancer can minimize adverse events while maximizing efficacy.

The Methylomic Biomarkers for Magnesium Deficiency and Colon Neoplasia Prevention study (R01CA202936A, PIs: Dai, Hou) aims to identify, in a randomized trial, sensitive methylation biomarkers for magnesium status which change with magnesium treatment. These biomarkers will be used for the personalized prevention of colorectal cancer. 

The Increasing HPV Vaccine Uptake in Community-based Pediatric Practices project (R01CA207401-0, PI: Hull)aims to determine the clinical effectiveness and cost-effectiveness of two modalities for delivering a multi-component practice facilitation intervention to increase HPV vaccination initiation and completion in community-based pediatric practices.

 

Projects that are not actively funded, but which have resources available to support new studies:

The Nashville Breast Health Study (R01CA100374, PI Zheng) is a population-based, case-control study of breast cancer conducted in Nashville, Tennessee since 2004. More than 4,000 breast cancer cases and controls were recruited in the study, the vast majority of whom provided an exfoliated buccal cell or saliva sample as a source of genomic DNA. Breast tissue samples have been collected in 60% of cases.

Tumor Markers and Recurrent Adenomas: A Follow-up Study (R01CA97386, PI Zheng) includes 1,200 patients with either an advanced adenoma or multiple adenomas recruited from Tennessee and Indiana. Polyp tissue samples from these patients have been analyzed for 18 tumor markers.

The Shanghai Breast Cancer Study (R01CA64277, R01CA90899, PIs Zheng/Shu) is a population-based, case-control study involving 3,500 breast cancer cases and an equal number of controls. In addition to in-person interview data, biological samples were collected from study participants. The resources from the study have supported multiple research and training grants.

The Fatty Acid Desaturase Activity, Fish Oil and Colorectal Cancer Prevention Trial (FADAFO, R01CA160938, PI: Murff) is a clinical trial designed to investigate whether fish oil reduces markers associated with colorectal cancer risk and if genetic determinates of fatty acid desaturase activity modify this effect.  The study collected blood, urine, adipose and rectal tissue samples.

The Shanghai Breast Cancer Survival Study (SBCSS, DAMD 17-02-1-0607, R01 CA118229, PI: Shu) is a population-based cohort study of 5,000 breast cancer survivors. The study includes multiple in-person interviews administered at 6-, 18-, and 36-month, 5-, and 10-year post-diagnosis, to obtain information on cancer diagnosis, treatment, progression, lifestyle factors, and quality of life. Medical charts were abstracted and tumor slides (85%) were collected. 96% of study participants provided DNA samples, 32% a blood sample and 53.2% a urine sample. In addition to recurrence and mortality, this study also collected information on depression, cognitive decline and bone density.

The Nashville Men’s Health Study (R01 CA121060, PI: Fowke) uses a multi-clinic, rapid-recruitment protocol to conduct molecular studies of prostate disease among men 40 years or older in the Nashville area.  Approximately 1,500 prostate cancer cases, 250 cases of prostatic intraepithelial neoplasia, and 3000 biopsy negative controls, and 400 healthy men have been recruited to the study with a participation rate exceeding 90%. The biospecimen collection includes spot urine and blood samples, collected from 100% of participants.

Personalized Prevention of Colorectal Cancer (R01 CA149633, PI: Dai) is a randomized placebo-controlled intervention trial to test whether reducing the calcium to magnesium intake ratio through supplementation of magnesium has effects on the associated biomarkers. The study has collected multiple rectal biopsies, samples of blood, urine, and stool, and tested apoptosis biomarkers (e.g. TUNEL and Bax), COX-2 (inflammation), Ki-67 (proliferation index), and TRPM7/TRPM6 in colorectal mucosa, as well as total erythrocyte magnesium and urinary excretion of prostaglandin E2 metabolite (PGE-M).

The Shanghai Endometrial Cancer Study (SECS, R01 CA92585, PI: Shu) is a population-based case-control study including 1,200 endometrial cancer cases and a similar number of controls. In addition to detailed dietary intake and other questionnaire-based information, the study also collected a blood or buccal cell sample and a urine sample from study participants.

Inflammatory Biomarkers and Colorectal Cancer Risk (R01 CA122364, PI: Yang) is a nested case-control study within the SWHS. Urine samples from 580 incident case-control pairs were measured for metabolite of prostaglandin E2 and F2-isoprostanes. Blood samples were measured for multiple pro-inflammatory markers.