Cancer Epidemiology

Melinda Aldrich, PhD, MPH, Jeffrey Blume, PhD
Funding Agency: NCI
Grant Number: 1 R01 CA251758-01A1

Current eligibility guidelines for lung cancer screening exclude a greater percentage of high-risk African Americans than whites. To remedy this, we will build a lung cancer risk prediction model for African Americans and use the new model to identify racially equitable screening strategies in the US population. 

Wei Zheng, Chris Haiman (University of Southern California)  Julie Palmer (Boston University)     
Funding Agency: NCI      
Grant Number:  R01CA202981 

The age-adjusted breast cancer mortality rate is more than 40% higher in African Americans than in whites for reasons poorly understood. To date, genome-wide association studies (GWAS) are mostly conducted in Asian and European descendants. However, only a few of the GWAS-identified risk variants can be directly replicated in African-ancestry women. GWAS are often not equipped to study structural variants and are inefficient for capturing low-frequency variants. These variants, although not yet adequately investigated, may contribute substantially to the heritability of breast cancer. In this consortium, we will generate new genomic data using whole genome sequencing and high-density genotyping arrays and consolidate GWAS data from existing studies to search genetic risk variants for breast cancer. Furthermore, we will evaluate how germline risk variants identified in this study and previous studies affect the major signaling pathways of breast cancer. More than 40,000 breast cancer patients and controls of African descent recruited from >20 studies conducted in the US and Africa will be included in this study. 

Xiao-Ou Shu
Funding Agency: NCI       
Grant Number: R03 CA183021

Lung cancer is the leading cause of cancer death 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 the 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 to 1) 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) evaluate whether calcium intake is associated with lung cancer prognosis. This consortium study was expanded to investigate the associations of dietary fat, prebiotic and probiotic foods, weight change and physical activity with lung cancer risk and prognosis. (Research activities are ongoing.)

Wei Zheng, Jirong Long
Funding Agency: NCI       
Grant Number: R01CA188214

Known genetic factors explain only a small fraction of colorectal cancer (CRC) heritability. This study expands our ongoing genome-wide association study (GWAS) in East Asians, the Asia Colorectal Cancer Consortium (including approximately 250,000 cases and controls), to identify new genetic susceptibility loci for CRC. We use fine-mapping and in vitro and in vivo functional analyses to discover functional variants and genes that drive the associations. The results of this study should help accelerate the translation of GWAS findings into disease prevention and treatment.

Loren Lipworth, Immaculata De Vivo, Wendy Setiawan  Margaret Du
Funding Agency: NCI 
Grant Number: R01CA250476

Endometrial cancer is becoming increasingly common, particularly in women with aggressive tumors who have poor outcomes. African American women have higher mortality than other racial/ethnic groups even after accounting for stage, histology, comorbid conditions, and treatment. Here, we will use the largest, most diverse population to date (including >1,000 African American and >2,000 non-African American endometrial cancer patients) in the Epidemiology of Endometrial Cancer Consortium (E2C2) to investigate endometrial tumor genomics, distinct risk factor profiles across tumor types, and the role of underlying tumor biology in driving this large survival disparity. 

Jirong Long, Fei Ye
Funding Agency: NCI
Grant Number:: R01CA247987

To conduct methylome-wide association study to identify novel genes and methylation loci for breast cancer.

Xiao-Ou Shu, Chen, Yu (NYU), Pei, Zhiheng (NYU)
Funding Agency:  NIH/NCI      

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 to prospectively investigate the oral microbiome and gastric cancer. The study also investigates whether antibodies of newly identified bacterial markers are related to gastric cancer. (Research activities are ongoing.)

Wei Zheng
Funding Agency: NIH
Grant Number:  R01 CA158473 

Known genetic risk factors explain about 28% of breast cancer heritability. 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. 

Qiuyin Cai, Jirong Long
Funding Agency: NIH/NCI     
Grant Number: R01 CA249863 

To systematically integrate transcriptome, methylome, and genome data to identify novel genes and methylation loci for lung cancer risk.

Staci Sudenga, Jessica Castilho
Funding Agency: NIH/NCI    
Grant Number: P30CA068485

Evaluate the potential biological importance of immunosenescence and risk of lung cancer among HIV-positive and -negative individuals.

Qiuyin Cai, Jirong Long
Funding Agency: NIMHD    
Grant Number:  R01MD015396

To investigate how individual and social contextual factors might affect DNA methylation and biological aging in racial minorities and identify potential mechanisms by which individual and social contextual factors might affect lung cancer risk in AAs and low SES EAs.

Wei Zheng, Jirong Long
Funding Agency: NCI
Grant Number: R01CA235553 

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. Since 2007, common genetic variants in ~200 loci have been identified in genome-wide association studies (GWAS) correlating to breast cancer risk. However, it is often difficult to translate GWAS findings to disease prevention and treatment since causal genes in most GWAS-identified loci are unknown. Furthermore, a large part of breast cancer heritability remains unexplained. We propose a well-powered transcriptome-wide association study (TWAS) to systematically search the whole transcriptome to identify genes associated with breast cancer risk using data from approximately 320,000 breast cancer patients and controls. We will also perform in vitro assays to functionally characterize promising genes identified in TWAS. Finally, we will evaluate whether TWAS-identified genes may contribute to racial differences in breast cancer risk by molecular subtypes. 

Christianne Roumie, Carlos G. Grijalva
Funding Agency: AHRQ
Grant Number: 1T32HS026122

This training program provides support for personalized mentoring for projects related to the learning healthcare system paradigm.

Wei Zheng
Funding Agency: NCI          
Grant Number: R01CA100374

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 and most participants provided an exfoliated buccal cell or saliva sample as a source of genomic DNA. Breast tumor tissue samples have been collected from approximately 1,400 participants with breast cancer. The main study ended in 2010. However, we continue to use data and biological samples collected in this study for multiple projects, including the first genome-wide association study of breast cancer in African American women.

Qiuyin Cai, Lynn Rosenberg
Funding Agency: NIH/NCI
Grant Number:  R01 CA207466 

To investigate whether oral microbiome may be associated with lung cancer risk among African Americans and European Americans.

Nikhil Khankari
Funding Agency: NIH/NCI
Grant Number: R00CA215360

Arachidonic acid, a long-chain omega-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, omega-3, also bind to the same enzymes involved in arachidonic acid metabolism; however, the resulting set of eicosanoids are anti-inflammatory. Thus, omega-3 PUFA metabolism could indirectly inhibit PGE2 production and reduce cancer risk. Multiple genetic variants have been identified to be associated with PUFAs. The goal of the proposed K99/R00 award 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.

Wei Zheng
Funding Agency: NIH
Grant Number: R01CA64277, RO1CA090899

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 between the ages of 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. 

Xiao-Ou Shu
Funding Agency: NIH/NCI
Grant Number: DAMD 17-02-1-0607, R01 CA118229

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 ages 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. (Research activities are ongoing.)

Xiao-Ou Shu
Funding Agency: NCI
Grant Number: R01 CA092585

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 major objectives of the study are to evaluate the roles 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. (Research activities are ongoing.)

Wei Zheng
Funding Agency: NIH
Grant Number: UM1CA182910

This population-based prospective cohort study was initiated in 1996, in which ~75,000 Chinese women living in Shanghai were recruited from 1996 to 2000. In addition to survey data, most study participants donated a blood or mouthwash sample and a urine sample at baseline. This cohort of women is being followed for incidence of site-specific cancers and cause-specific mortality. Five in-person follow-up surveys have been completed, each with a response rate greater than 90%. The resources from this study have supported more than 200 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, unique exposure patterns, and disease spectrum, provides exceptional opportunities to address many significant hypotheses that cannot be adequately investigated in other existing cohorts.

Wei Zheng, Wen Wanqing
Funding Agency: NIH
Grant Number: UM1CA182910

This population-based prospective cohort study was initiated in 1996, in which ~75,000 Chinese women living in Shanghai were recruited from 1996 to 2000. In addition to survey data, most study participants donated a blood or mouthwash sample and a urine sample at baseline. This cohort of women is being followed for incidence of site-specific cancers and cause-specific mortality. Five in-person follow-up surveys have been completed, each with a response rate greater than 90%. The resources from this study have supported more than 200 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, unique exposure patterns, and disease spectrum, provides exceptional opportunities to address many significant hypotheses that cannot be adequately investigated in other existing cohorts.

Song Yao (Roswll Park Cancer Institute), Wei Zheng (VUMC)  John Carpten (USC)  Julie Palmer (Boston University)
Funding Agency: NIH
Grant Number: R01CA228156 

Women of African ancestry are disproportionately afflicted with triple-negative breast cancer (TNBC), and bear the highest mortality rate of all populations from the disease in the U.S. In this research consortium, we propose to characterize the mutational landscape of TNBC in African American women by performing whole-exome sequencing and RNA-sequencing. We will then compare significantly mutated genes and mutational signatures between African- and European-ancestry women. Finally, we will investigate genetic and environmental factors in relation to somatic mutations. This research will greatly advance the field of breast cancer research by characterizing the tumor mutational landscape in African American women and determine whether cancer biology at the somatic mutation level differs by ancestral populations. 

Wei Zheng, Martha Shrubsole
Agency: NIH
Grant Number: U01CA202979 

The SCCS was initiated in 2001. Nearly 86,000 adults aged 40-79 at cohort entry were recruited during 2002-2009 across 12 southern states, mostly at Community Health Centers (institutions providing basic health and preventive services in underserved areas). By design, two-thirds of the cohort was selected to be African American and the remainder predominantly non-Hispanic white to help remedy the underrepresentation of African Americans in health studies and enable direct black/white comparisons. Most of the cohort members, both black and white, had low income and education levels. In addition to detailed survey data, biospecimens were collected from more than 76,000 cohort members at baseline, with blood obtained and stored for approximately 39,000, mouth rinses/saliva for 38,000, and urine for 24,000, so that genomic DNA could be extracted from nearly 90% of participants. In 2018, we initiated stool sample collection and have collected these samples from ~8,500 cohort members. This cohort is being followed for incidence of site-specific cancers and cause-specific mortality. Data and biospecimens collected in the SCCS have been used to support large numbers of epidemiologic and genetic studies of cancer and other chronic diseases. 

Wei Zheng, Harvey Murf
Funding Agency:  NIH
Grant Number: P50CA095103 

 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. 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 VUMC 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. Recruitment for this study ended in 2010; however, data and biological samples collected in this study continue to be used in multiple studies. The resources from this project have supported multiple externally funded studies, including six K07 or K99/R00 grants for career development of junior investigators and multiple R01-funded studies.

Staci Sudenga, Wei Zheng
Funding Agency: NCI
Grant Number: K07CA225404

The proposed research project aims to evaluate the potential biological importance of tumor infiltrating lymphocytes (TILs) in patients with pre-malignant anal lesions and anal cancer. Through the career development award, Dr. Sudenga will develop skills in tumor immunology and cancer research to become an independent investigator in infection-related cancer epidemiology.

Wei Zheng
Funding Agency:  NIH
Grant Number: R01CA097386

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.

Melinda Aldrich
Funding Agency: NCI
Grant Number: 1U01CA253560-01

This study examines the interplay of biologic susceptibility, along with social, behavioral, and community-level determinants contributing to lung cancer risk in both African American and White individuals. 

Melinda Aldrich
Funding Agency: Lung Cancer Research Foundation

This project will provide a deeper understanding of which factors influence lung cancer stage of diagnosis among community health center patients and provide outreach to the community about the importance of early detection for lung cancer. 

Wilbroad Mutale, MBChB, PhD, Douglas C Heimburger, MD, MS
Funding Agency: NIH
Grant Number: 5D43 TW009744

UVP trains Zambian PhD- and postdoctoral HIV researchers, equipping them with research skills in non-communicable complications and comorbidities of HIV, while expanding the University of Zambia (UNZA) / University Teaching Hospital's (UTH) research training and investigative capacities.

Xiao-Ou Shu, Setiawan, Veronica (USC)
Funding Agency:  NCI
Grant Number: R01 CA227133

Detecting pancreatic cancer at an early, asymptomatic stage is a top priority for reducing incidence and mortality of this most fatal disease. This multi-center study utilizes pre-diagnostic blood samples collected in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Southern Community Cohort Study (SCCS), Multiethnic Cohort Study (MEC), Shanghai Women's Health Study (SWHS), and Shanghai Men's Health Study (SMHS) to discover and validate circulating microRNAs as biomarkers for pancreatic cancer early detection and risk assessment. (Research activities are ongoing.)

Xiao-Ou Shu
Funding Agency: NCI            
Grant Number: T32 CA160056

This NCI-funded training program is designed to build an elite class of epidemiologists to lead multidisciplinary collaborative research in cancer. The program delivers 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. For more information, please visit: https://www.vumc.org/magec/welcome. (Research activities are ongoing.)

Douglas C Heimburger, MD, MS, Muktar Aliyu, MBBS, DrPH
Funding Agency: NIH/NIAID
Grant Number: 2D43 TW009337

Vanderbilt-Emory-Cornell-Duke (VECD) is one of six consortia that comprise the Fogarty Global Health Program for Fellows and Scholars. The purpose of this program is to provide mentored global health research training opportunities in low- and middle-income countries (LMICs) for pre- and post-doctoral candidates from the U.S. and LMICs. The program is sponsored by the Fogarty International Center (FIC) and several collaborating Institutes and Centers at the National Institutes of Health (NIH). Multiple training sites are available through VECD.