Cancer Epidemiology

  • PI:  Shu, Xiao Ou     Funding Agency: NCI       Grant No.:  R03 CA183021 
    Lung cancer is the leading cause of cancer deaths worldwide. Although cigarette smoking is the major cause, up to 25% of lung cancer cases are never smokers.  Nutritional factors may affect multiple steps in lung carcinogenesis and cancer progression. Funded by NCI, we launched a large-scale pooling project that involves thirteen large prospective cohorts, including nearly two million men and women from the United States and countries in Europe and Asia. The major objectives for the study are 1) to prospectively investigate whether calcium intake is associated with the risk of lung cancer and whether such associations differ by smoking, sex, race or major determinants of vitamin D status; and 2) to evaluate whether calcium intake is associated with lung cancer prognosis. Additional ancillary projects investigate the associations of weight change and physical activity in association with lung cancer risk and prognosis.

  • PI:  Zheng, Wei      Funding Agency: NCI       Grant No.:  R37 CA070867 
    Description:  Using data and biological samples collected from the Shanghai Women’s Health Study (SWHS), we are evaluating several important etiologic hypotheses for cancer that are difficult to investigate in other existing cohort studies. We are studying dietary factors that could potentially reduce the risk of cancer. We also conduct nested case-control studies to evaluate biomarkers that could potentially be used for cancer risk prediction and assessment.

  • PI:  Boice, John Dunning Jr.     Funding Agency: NCI       Grant No.: U01 CA137026 
    The lifetime risk of cancer is being quantified among 125,000 United States atomic veterans who participated at one or more of the 230 aboveground atmospheric nuclear weapons tests at the Nevada Test Site or the Pacific Proving Ground between 1946 and 1958. Reliable estimates of radiation dose for individual atomic veterans are being made which were not possible in previous investigations. Advances in dose reconstruction methods will permit dose-response evaluations and risk quantification. New knowledge will be sought on specific cancer risks following protracted low-dose exposure to external and internal radiation, including the inhalation and ingestion of plutonium, uranium and radioactive fission products. The hypothesis to be tested is that chronic low-dose radiation exposure some 50 to 60 years ago can be linked to increases in leukemia and other diseases, including coronary heart disease.

  • PI: Zheng, WeiLong, Jirong     Funding Agency: NCI        Grant No.: R01 CA188214 
    Description: Known genetic factors explain only a small fraction of colorectal cancer (CRC) heritability. This study cost-efficiently expands our ongoing genome-wide association study (GWAS) in East Asians to identify new genetic susceptibility loci for CRC.  We use fine-mapping and functional analysis to discover functional variants and genes that drive the associations. A novel stem-cell-driven mouse model of colonic neoplasia will be used to further determine specific CRC genes and susceptibility alleles in selected loci identified in GWAS. This GWAS expansion is the first large study in East Asians to comprehensively search for genetic risk factors for CRC. We anticipate identifying functional variants and novel genes/pathways for CRC to improve the understanding of the biological mechanisms through which GWAS-identified loci contribute to CRC risk. This information will help accelerate the translation of GWAS findings into disease prevention and treatment. 

  • PI:  Zheng, Wei ; Long, Jirong      Funding Agency: NCI          Grant No.:   R01 CA148667 
      This study comprises two projects to significantly advance our understanding of the genetic basis for breast cancer and the methodology used for genetic epidemiologic research. The first project, a genome-wide association study (GWAS) based on the newly-established Asia Breast Cancer Consortium, analyzes data from 11 studies conducted among Asian women living in various parts of the world.. In the second project, we sequence eight GWAS-mapped regions with a goal of identifying additional genetic risk variants, particularly low-frequency risk variants, for breast cancer. This is the only well-powered genetic study of its kind conducted in Asian women, and thus offers the opportunity to discover genetic variants for breast cancer that are unlikely or more difficult to identify in GWAS of other populations.

  • PI: Zheng, WeiPotter, John         Funding Agency: NCI      Grant No.: R03 CA153116 
    Description: In Asian countries, in the wake of lifestyle changes (reduced physical activity, increased prevalence of obesity and cigarette smoking, and heavy alcohol consumption), the burden of chronic diseases has increased substantially in recent decades. Each of these modifiable factors has been linked to premature death; however, the overall impact of these factors on total and cause-specific mortality is unclear. This study will also evaluate the association of central obesity with total and cause-specific mortality. This study is being conducted as part of the Asia Cohort Consortium, in which data from more than 1 million individuals recruited in approximately 20 cohort studies have been harmonized and analyzed to quantify the association of BMI and tobacco smoking with total and cause-specific mortality (Zheng W, et al, NEJM, 2011; 364(8):719-29; Zheng W, et al, PLoS Medicine, 2014; 11(4):e1001631). Study results will inform the design of effective programs tackling the emerging epidemic of chronic diseases and reduce premature death in Asian countries.

  • PI:  Shrubsole, Martha       Funding Agency:  NCI        Grant No.: R03 CA189455 
    Description:  Despite fortification or supplementation and even adequate sunlight exposure, vitamin D insufficiency or deficiency is still relatively common in the US.  One striking observation is that a large portion of the inter-person variation in serum 25-hydroxyvitamin D (25(OH)D) levels is unexplained. Magnesium (Mg), the second most abundant intracellular cation, plays a critical role in the synthesis and metabolism of vitamin D. Previous in vitro studies have indicated that the activities of three major enzymes determining 25(OH)D level may be Mg-dependent. We are evaluating whether Mg supplementation affects serum 24,25(OH)D and the ratio of 24,25(OH)D/ 25(OH)D, and, thus, improves vitamin D resistance (i.e. insensitivity to vitamin D supplementation) and reduces risks of diseases related to vitamin D deficiency/resistance (e.g. colorectal cancer) using data and serum samples collected in the Personalized Prevention of Colorectal Cancer Trial, a randomized controlled intervention trial of Mg supplementation.

  • PI: Cai, Quiyin       Funding Agency: NCI       Grant No.: U01 CA161045 
    Description:We are conducting a whole-exome sequencing study to systematically search the entire coding region in the human genome to detect lung cancer susceptibility genes and variants. This study is built on the resources established in the Shanghai Women’s Health Study, Guangzhou Lung Cancer Study, and the Female Lung Cancer Consortium in Asia, all of which are conducted among East-Asian women. The specific aims of the study are as follows; all cases and controls are female never-smokers. Aim 1 is to sequence the whole exome of 600 NSCLC cases and 600 controls (Stage 1). Aim 2 is to validate variants in approximately 350 promising genes identified in Aim 1 in 2,500 NSCLC cases and 2,500 controls (Stage 2). Aim 3 is to validate approximately 15 genes from Stage 2 in an additional 2,500 NSCLC cases and 2,500 controls (Stage 3). To our knowledge, this is the first large association study of lung cancer conducted among never-smokers using whole-exome sequencing.

  • PI: Murff, Harvey       Funding Agency: NCI       Grant No.: R01 CA160938 
    Description: Observational studies have suggested that the n-3 polyunsaturated fatty acids, eicosapentanoic acid and docosahexanoic acid, may reduce the risk of colorectal cancer. Our hypothesis is that individuals with lower activity of fatty acid desaturase-1(FADS1) will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity due to lower production of endogenous arachidonic acid. To test this hypothesis we will recruit 150 participants and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. Our first factor will be FADS1 genotype (GG, GT, and TT) and our second factor will be fish oil supplementation (fish oil versus placebo). Our specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention.

  • PI: Chen, Yu (NYU), Shu, Xiao-Ou, Pei, Zhiheng (NYU)       Funding Agency: NIH/NCI    Grant No.: 1R01 CA204113-01
    Description: Gastric cancer is a major cancer worldwide. H. pylori infection plays a critical role in gastric cancer initiation but colonizes gastric precancerous lesions poorly.  The loss of H. pylori and impairment of acid secretion in these lesions may facilitate the colonization of other bacteria, particularly those from the oral cavity, into the stomach, which may promote gastric carcinogenesis. To test this hypothesis, this study uses pre-diagnostic oral wash samples from the Shanghai Women's Health Study, Shanghai Men's Health Study, and Southern Community Cohort Study in the first prospective case-control study of the oral microbiome and gastric cancer. The study also investigates whether antibodies of the newly-identified bacterial markers are related to gastric cancer. This study will provide complementary and comprehensive data that may be useful to understand the etiology and epidemiology of gastric cancer, as well as to help in the development of future interventions and risk stratifications for gastric cancer.

  • PI: Fowke, Jay H.     Funding Agency: NCI     Grant No.: R01 CA121060 
    Description: The purpose of this study is to investigate the associations between obesity, prostate cancer, and high-grade prostatic intraepithelial neoplasia (PIN). Toward this goal, we developed a multi-centered rapid-recruitment protocol targeting men seeking a diagnostic prostate biopsy within any urology clinic in metro Nashville, TN.  Trained staff measure body size and body composition using bioelectric impedance analysis, collect pre-diagnosis blood and urine for biomarker and genetic analyses, administer a research lifestyle questionnaire, and perform medical chart review for clinical and pathology data.  Genetic and molecular markers of obesity are investigated toward prostate cancer and PIN risk.

  • PI:  Zheng, WeiMurff, Harvey     Funding Agency: NCI      Grant No.: P50 CA095103 
    Description:    This project was conducted as part of the Vanderbilt SPORE in GI Cancer (PI, Robert Coffey).
    Most colorectal cancers arise from adenomatous polyps, and a large proportion of adenoma patients develop new (metachronous) adenomas after their initial polypectomy. This study evaluates both genetic susceptibility risk variants and tumor markers in relation to the risk of metachronous adenomas. Approximately 1700 patients with multiple or advanced adenomas are included in this study. These patients are being followed for adenoma recurrence. Biological samples collected from these patients are being analyzed for genetic and epigenetic markers. It is anticipated that this study will provide critical information valuable in identifying high-risk adenoma patients for intensive follow-up.

  • PI:  Zheng, Wei        Funding Agency: NCI        Grant No.:  R01 CA124558 
    Description:   Genetic factors play an important role in the etiology of breast cancer.  With recent significant advances in high-throughput genotyping technologies, it has become feasible to conduct genome-wide association studies (GWAS) to systematically evaluate genetic risk factors for breast cancer. We initiated a pilot study in 2005 providing the proof-of-principle evidence that novel genetic risk variants for breast cancer can be identified in GWAS. This full-scale study, the first GWAS of breast cancer conducted in non-European descendants, initiated in 2008, uses resources of multiple studies. The results from the study will improve the understanding of breast cancer biology and genetics and could potentially be used to identify women at high risk for breast cancer.

  • PI:  Zheng, Wei          Funding Agency: NCI           Grant No.:  R01 CA158473 
    Description:  Known genetic risk factors explain about 28% of heritability for breast cancer. Emerging evidence strongly suggests that a large fraction of the heritable risk for breast cancer and other complex diseases may be difficult to identify using conventional methods and genome-wide association studies (GWAS). This study systematically searches the entire coding region in the human genome to identify new genetic susceptibility factors for breast cancer. This is the first large association study for breast cancer using whole exome sequencing. It is anticipated that this study will identify novel genes and pathways to significantly improve our understanding of breast cancer genetics and biology. Newly identified genes could serve as targets for novel cancer treatment and improved cancer screening and risk assessment.

  • PI: Epplein, Meira          Funding Agency: NCI         Grant No.: R01 CA174853 
    Description: Infection with Helicobacter pylori is the leading risk factor for gastric cancer, the second-most deadly and fourth-most common cancer in the world, yet only a fraction of those infected will develop the disease. Utilizing novel H. pylori multiplex serology in a nested case-control study in China, we have recently found a novel biomarker panel that could identify individuals with a 10-20% absolute risk of gastric cancer, and are now seeking to determine if we can replicate and validate this finding in other prospective cohorts in East Asia most likely to be infected with similar bacterial strains. As H. pylori eradication therapy can effectively reduce gastric cancer incidence and mortality, a validated risk prediction model in high-incidence populations will create the opportunity to substantially decrease the burden of gastric cancer through targeted prevention strategies among H. pylori-infected individuals at highest risk, while reducing unnecessary antibiotic use among those at low risk.

  • PI: Epplein, Meira         Funding Agency: VICTR          Grant No.: VR4676 
    Description: It has been suggested that Helicobacter pylori, a known risk factor for gastric cancer, may also increase risk of colorectal cancer, and two recent meta-analyses of published studies of the association of H. pylori with colorectal cancer incidence have found a 40% to 50% increase in odds for those infected with the bacteria. The present study seeks to further our understanding of the H. pylori–colon cancer association by measuring serum gastrin levels and assessing their individual association with H. pylori strain-specific infection and with colorectal cancer risk, and the possibility of gastrin as part of the pathway from H. pylori infection to development of colon cancer, among an under-studied population with a high prevalence of H. pylori, the Southern Community Cohort Study.

  • PI: Epplein, Meira         Funding Agency: NCI          Grant No.: K07 CA151782 
    Description: Inflammation has been hypothesized to be involved in the etiology of multiple cancers, including those of the liver (HBV, HCV), cervix (HPV), and stomach (Helicobacter pylori), and it has even been postulated that cancer is a situation of unhealed infection. The aim of the research plan proposed in this award is to be able to identify the most virulent H. pylori strains and the most vulnerable populations to gastric cancer, the second leading cause of death from cancer worldwide, so that we can more appropriately assess risk and focus diagnostic testing and eradication therapy to prevent the development of gastric cancer. This investigation into the bacteria-host-environment risk factors related to gastric cancer, including levels of host inflammatory cytokines, will both further the field of gastric cancer etiology and provide a strong training opportunity for a future career in the broader field of inflammation and cancer.

  • PI: Epplein, Meira        Funding Agency: NCI          Grant No.: R01 CA190428 

    Colorectal cancer is the third most common and deadly cancer in the US, and there is evidence that colorectal cancer incidence is increasing among both men and women younger than 50 years of age, who are also more likely to be diagnosed with late-stage disease. Additionally, there is a significant racial disparity, in that African American men and women experience a higher incidence of colorectal cancer compared to white men and women, and an even higher rate of death from colorectal cancer compared to the white population. The current project seeks to evaluate the novel association between Helicobacter pylori protein-specific infection and colorectal cancer risk, building the groundwork for significantly strengthening colorectal cancer prevention and screening strategies with a new risk biomarker, as well as the possibility of identifying an exposure that is proven to be modifiable through the use of eradication therapy, and may be modifiable by a regimen of regular aspirin use.

  • PI: Yang, Gong          Funding Agency: NCI          Grant No.: R01 CA122364
    Description: This is a nested case-control study within the Shanghai Women’s Health Study, to evaluate the association of colorectal cancer (CRC) risk with measures of several key products of chronic inflammation and oxidative stress, and with related genetic markers. Urine samples collected at baseline were measured for PGE2 metabolite, F2-isoprostanes and its major metabolite using LC/GC MS-based methods. Baseline blood samples were measured for CRP, proinflammatory cytokines and their soluble receptors. Genomic DNA was assayed for polymorphisms in genes involved in redox balance and PGE2 production, metabolism and signaling. This study may contribute to further understanding the role of inflammation and oxidative stress in the etiology of CRC and to the development of new strategies for the assessment of CRC risk and prevention. Funded by the National Cancer Institute.

  • PI: Cai, Quiyin          Funding Agency: DOD          Grant No.: LC120707
    Description: We hypothesize that antibody profiles or signatures could be identified and used to distinguish lung cancer cases from controls at a very early stage by using a random peptide array. To test this hypothesis, we are conducting a nested case-control study within a prospective, population-based cohort study. The specific aims for the proposed study are: Aim 1: To conduct antibody profiling assays in 100 incident lung cancer cases and 100 matched controls using a novel, large, peptide array. Pre-diagnostic plasma samples will be used for the peptide array assays. Aim 2: To perform statistical analyses to identify antibody profiles or signatures that differ significantly between participants who subsequently develop lung cancer and participants who remain lung cancer free. The proposed study holds significant potential to develop a biomarker panel for lung cancer risk assessment and/or early diagnosis.

  • PI: Murff, Harvey         Funding Agency: NCI          Grant No.: R01 CA143288 
    Description: Chronic inflammation is contributors to colorectal carcinogenesis. Eicosapentanoic acid exhibits anti- inflammatory actions while arachidonic acid, an omega-6 polyunsaturated fatty acid, appears pro- inflammatory. Our overarching hypothesis is that individuals with increased dietary ratios of arachidonic acid to eicosapentanoic acid will have an increased risk of colorectal adenoma and that this increased risk is mediated through pro-inflammatory eicosanoids and increased oxidative stress. The specific aims of this research proposal are: 1) To test the hypothesis that a greater erythrocyte phospholipid membrane arachidonic acid to eicosapentanoic acid ratio is associated with an increased risk of colorectal adenomas; 2) To test the hypothesis that an increase in urinary levels of F2-isoprostanes is associated with an increase risk of colorectal adenomas and; 3) To test the hypothesis that a greater arachidonic acid to eicosapentanoic acid ratio is associated with increased levels of prostaglandin E2 and urinary F2-isoprostanes.

  • PI: Wang, Thomas: Shu, Xiao-OU; Gerzten, Robert (Harvard University)  Funding Agency: NIH/NIDDK  
    Grant No.:  1R01DK108159-01A1
    Description:Type 2 diabetes mellitus (DM) is a major cause of morbidity and mortality worldwide. The pathogenesis of DM reflects a complex interplay of genetic, dietary, and environmental exposures affecting multiple pathways. It is also increasingly recognized that there is phenotypic heterogeneity among individuals who develop DM. Using the resources from the Shanghai Women’s Health Study and Shanghai Men’s Health Study, this study comprehensively evaluates metabolomic profiling to identify metabolites associated with incident DM in a population with low prevalence of diabetes. This research includes a nested case-control study and a separate case-cohort study to replicate findings, as well as an assessment of whether the addition of metabolites improves the ability to predict the risk of DM in Asians, compared with risk factors alone, and whether the metabolite predictors are associated with mortality and cardiovascular events.

  • PI: Shrubsole, Martha          Funding Agency:  NCI           Grant No.: R03 CA195660 
    Esophageal adenocarcinoma (EA) incidence in the western world has rapidly increased but survival remains low. Most EA arises in Barrett’s Esophagus (BE) although the etiology of both diseases are poorly understood and there are very few known modifiable risk factors. Recent studies suggest DNA hypomethylation may be a key factor that appears early in carcinogenesis. The methyl donor S-adenosylmethionine (SAM) from the methionine cycle is involved in both one-carbon metabolism (OCM) and DNA methylation. We previously found higher plasma SAM levels were associated with decreased neoplasia risk in two studies. We also found dietary OCM factors have a role in BE and EA risk. Thus, we are testing the hypothesis that methionine cycle metabolism has a role in EA carcinogenesis in a study using plasma samples from a population-based case-control study of BE and EA based in Northern Ireland.

  • PI: Fowke, Jay H.          Funding Agency: NCI             Grant No.: R03 CA159398 
    Description: This analysis uses data from a consortium of 13 prospective cohort studies across Asia to investigate lifestyle risk factors for prostate cancer in regions where prostate cancer is relatively rare and there is substantially less screening.

  • PI:  Zheng, Wei             Funding Agency: NCI            Grant No.: R01 CA100374 
    This study is a population-based, case-control study of breast cancer conducted in Nashville, Tennessee since 2004. Its primary aim is to study genetic factors and gene-environment interactions in relation to breast cancer risk. Approximately 6,000 breast cancer cases and controls have been recruited; the vast majority of participants provided an exfoliated buccal cell or saliva sample as a source of genomic DNA. Breast tumor tissue samples have been collected from approximately 1400 participants with breast cancer. The main study ended in 2010. However, recruitment for breast cancer patients of African ancestry has been continued and expanded to other regions, including greater Tennessee, South Carolina and Georgia. Data and biological samples collected in this study have been used in multiple projects, including the first genome-wide association study of breast cancer in African Americans.

  • PI: Khankari, Nikhil            Funding Agency: NCI            Grant No.: K99 CA215360
    Description: Arachidonic acid, a long-chain ω-6 polyunsaturated fatty acid (PUFA), has been demonstrated to affect carcinogenesis in animal and in vitro studies. The effect of arachidonic acid is believed to be largely due to overproduction of the eicosanoid, prostaglandin E2 (PGE2). The other class of PUFAs, ω-3, also bind to the same enzymes involved in arachidonic acid metabolism; however, the resulting set of eicosanoids are anti-inflammatory. Thus, ω-3 PUFA metabolism could indirectly inhibit PGE2 production and reduce cancer risk. Over the past few years, multiple genetic variants have been identified to be associated with PUFAs. The goal of this study is to elucidate the potential causal association between long-chain PUFAs and colorectal tumor risk using Mendelian randomization (MR), an approach that may avoid potential pitfalls of conventional observational epidemiologic research and utilizes genetic variation as a proxy for exposures.

  • PI: Aldrich, Melinda          Funding Agency: DOD          Grant No.: W18XWH-11-LCRP-EI
    Description:  This study seeks to find the reasons for poor survival after a lung cancer diagnosis, especially among people at greatest risk. Discovery of genes that affect lung cancer survival can identify new targets for drug treatments and lead to the development of important clinical tests to improve survival of lung cancer. Understanding the reasons for poor survival will lead to better quality of care and treatments for persons with lung cancer.

  • PI: Shrubsole, Martha          Funding Agency:  NCI           Grant No.: R03 CA183019 
    Description:  The human colorectum is host to billions of bacteria which comprise the microbiota. Previous epidemiological studies of the colorectal microbiome are few, and with very small sample sizes. Furthermore, before microbial biomarkers can be adopted in large-scale epidemiologic studies of colorectal neoplasia, two key methodological or practical questions remain. First, what source(s) of sample(s) is/are most appropriate for analysis of the human colorectal microbiome, and, second, whether a spot sample is adequately reliable for representing the colorectal microbiome in relation to colorectal carcinogenesis. This study will address these two key issues using serial samples collected in a randomized trial, laying a foundation for future epidemiologic studies and intervention tria

  • PI: Shu, Xiao Ou           Funding Agency: NCI            Grant No.: DAMD 17-02-1-0607, R01 CA118229 
    Description: The Shanghai Breast Cancer Survival Study (SBCSS) is a population-based cohort study of 5,042 women who were diagnosed with primary breast cancer between age 25 and 74 years. Participants were identified from the population-based Shanghai Cancer Registry and recruited to the study approximately 6 months after cancer diagnosis between April 1, 2002 and December 31, 2006 (response rate: 80.1%). The study has completed multiple in-person interviews administered at 6, 18, 36, and 60 months after diagnosis, which collected information on cancer diagnosis, treatment, progression, lifestyle factors, and quality of life. The 10-year post-diagnosis survey is ongoing. Medical charts were abstracted to verify cancer diagnosis and initial treatments; tumor slides were collected. The vast majority of study participants (96%) provided DNA samples to the study. The SBCSS has published many high impact papers addressing the influences of lifestyle, psychosocial, and genetic factors on cancer outcomes and quality of life among survivors.

  • PI: Zheng, Wei, Shu, Xiao Ou          Funding Agency: NCI            Grant No.: R01 CA090899R01 CA064277 
    Description: The Shanghai Breast Cancer Study (SBCS) is a population-based, case-control study funded by NCI since 1996 to investigate lifestyle factors, genetic susceptibility, and other biomarkers associated with breast cancer risk and survival. Included in the study are approximately 3,500 breast cancer cases aged between 25 and 70 years and an equal number of community controls recruited among female residents of Shanghai, China. 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 and provided opportunities for many graduate students and postdoctoral fellows to conduct research. To date, over 150 research papers have been published from the SBCS addressing a wide range of significant issues related to dietary, lifestyle, environmental, and genetic contributions to breast cancer risk and prognosis.

  • PI: Shu, Xiao Ou            Funding Agency: NCI            Grant No.: R01 CA82729, UM1 CA173640 
    Description: The Shanghai Men’s Health Study (SMHS), funded by NCI since 2001, is a population-based cohort study of 61,482 men aged between 35 and 75 years and recruited from 2002 to 2006. At baseline, detailed information on dietary intakes, personal habits, occupational history, medical history, and other lifestyle factors was collected, and anthropometrics were measured. Blood or buccal cell, and  urine samples were collected from 89% of participants. The cohort has been followed through multiple in-person surveys to update exposure information and through record linkages with the population-based Shanghai Cancer Registry and Shanghai Vital Statistics Registry to obtain information on cancer occurrence and survival status. Over the years, SMHS data and biological samples have been used to evaluate many important etiologic hypotheses addressing the contributions of environmental, dietary, lifestyle, and genetic exposures to the development of cancer and other chronic diseases. The cohort supports multiple studies, including over 25 consortium projects.

  • PI: Shu, Xiao Ou          Funding Agency: NCI            Grant No.: R01 CA092585 
    Description: The Shanghai Endometrial Cancer Study is a population-based, case-control study of 1,204 endometrial cancer cases and 1,212 controls who were aged between 30 and 69 years and recruited between 1997 and 2003. The study recently recruited an additional 587 endometrial cancer patients. The major objectives of the study are to evaluate the role of and interactions between hormonal, dietary, and other lifestyle factors and genetic susceptibility in endometrial carcinogenesis. 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 participants. The study has published multiple papers reporting novel findings on dietary risk/protective factors and genetic susceptibility factors. The SECS is one of the largest epidemiological studies of endometrial cancer and is a major contributor to the international Epidemiology of Endometrial Cancer Consortium.

  • PI: Zheng, Wei           Funding Agency: NCI            Grant No.:   UM1 CA182910 
    Description: This population-based prospective cohort study was 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. Approximately 50% of study participants who did not donate a blood sample provided a sample of exfoliated buccal cells. This cohort of women is being followed for incidence of site-specific cancers and cause-specific mortality through a combination of in-person surveys and record linkages with population-based registries. Four in-person follow-up surveys have been completed, each with a response rate greater than 90%. The resources from this study have supported multiple studies, including approximately 40 international research consortia, to address etiologic hypotheses for cancers and other chronic diseases. The SWHS, with its large sample size, wealth of resources, and unique exposure patterns and disease spectrum, provides exceptional opportunities to address many significant hypotheses that cannot be adequately investigated in other existing cohorts.

  • PI: Yang, Gong          Funding Agency: NCI          Grant No.: R01 CA200999 
    To evaluate whether exposure to endogenous estrogens and plant estrogens (phytoestrogens) is related to lung cancer risk and mortality in nonsmoking women.

  • PI:  Zheng, WeiReid Ness          Funding Agency: NCI            Grant No.: P50 CA90949 
    Description:  This project was conducted as part of the Vanderbilt SPORE in GI Cancer (PI, Robert Coffey). Recruitment for this study ended in 2010; however, data and biological samples collected in this study continue to be used in multiple studies. The primary aim of this study is to evaluate lifestyle factors and biomarkers for the risk and recurrence of colorectal polyps. Participants were recruited from patients who were scheduled for clinically-indicated colonoscopy at the VU Hospital and the VA Tennessee Valley Healthcare System. More than 7,000 patients were recruited and completed a telephone interview. Biological samples, including blood, exfoliated buccal cells, polyp tissues, and rectal biopsies, were collected from eligible subjects. The resources from this project have supported multiple externally-funded studies, including three K07 grants for career development of junior investigators and multiple R01-funded studies.

  • PI: Zheng, Wei           Funding Agency: NCI            Grant No.: R01 CA97386 
    Description: This study officially ended in 2008, but the resources it established continue to be used to support other studies. The aim of this study was to study biomarkers that can be used to predict adenoma recurrence after initial polypectomy. Approximately 1,200 patients with either an advanced adenoma or multiple adenomas were recruited from Tennessee and Indiana. Polyp tissue samples from these patients have been used to evaluate multiple tumor markers.

  • PI:  Aldrich, Melinda       Funding Agency:  NCI         Grant No.: K07 CA172294 
    Description : African Americans have the greatest risk of lung cancer compared to all other racial/ethnic groups, yet have been historically underrepresented in research. This study seeks to identify genetic factors contributing to lung cancer in African Americans and ultimately reduce their disease occurrence. This investigation into the genetics and environmental risk factors related to lung cancer will both further the field of lung cancer and also provide a strong training opportunity for the candidate to have a successful career in the broader field of genetics and cancer.

  • PI: Cai, Quiyin          Funding Agency: DOD          Grant No.: W81XWH-15-2-0053
    Lung cancer is the number one cause of cancer-related deaths. While low-dose helical CT (LDCT) scanning has demonstrated a degree of success with a reduction in lung cancer mortality by 20%, it has a high false discovery rate. It is conceivable that a complementary biomarker, from a non-invasively collected biospecimen such as urine, could be utilized to increase the specificity of LDCT and significantly improve current screening methods. In this DOD-funded project, we are collaborating with Dr. Curtis Harris at NCI to investigate the performance of previously discovered urinary metabolomic biomarkers. Validation study will be conducted using data and urine samples from the Southern Community Cohort Study. Identified urinary metabolomics markers may improve the performance of currently existing risk, diagnostic, and prognostic lung cancer classifiers in the high risk populations.

  • PI: Heimburger, Douglas       Funding Agency: FIC       Grant No.: R25 TW009337 
    Description: This project aims to nurture a new generation of global health researchers through a collaborative training program with overseas research institutions from low and middle-income countries with which our universities have worked for decades.

  • PI: Shu, Xiao Ou       Funding Agency: FIC            Grant No.: D43 TW008313 
    Description: The Vanderbilt-Shanghai Chronic Disease Research Training Program, funded by the NIH Fogarty International Center, aims to train a new generation of scientists and future leaders in chronic disease research in China and equip them with the expertise to conduct multi-disciplinary chronic disease research and build research and training capacity, as well as establish long-term international collaborative partnerships in chronic disease research and prevention. The training program includes the organization of two workshops and an international conference on chronic disease research and prevention in China and the training of 18 medium-term (6-month) and long-term (12-month) visiting fellows at the Vanderbilt Epidemiology Center. The program primarily focuses on advanced training in epidemiological and biostatistical methodology, design and execution of multidisciplinary research projects, and building expertise in cancer, cardiovascular disease, and diabetes research, as well as grant writing skills.

  • PI: Shu, Xiao OuHeimburger, Douglas       Funding Agency: NCI            Grant No.: R25 CA160056 
    Description: This program is designed to address the urgent need to build an elite class of epidemiologists to lead the new era of multidisciplinary collaborative research in cancer by delivering individualized didactic and research training to equip postdoctoral fellows from a variety of disciplines with the methodological tools, practical laboratory and survey-research knowledge, and hands-on research and grant writing experience necessary to launch independent careers in the molecular and genetic epidemiology of cancer.