Nutritional Epidemiology

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.)

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.

PIs: Wang, Thomas, Shu, Xiao-Ou, Gerzten, Robert (Harvard University)
Agency: NIH/NIDDK
Grant No.: R01DK108159-01A1

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 well recognized that there is phenotypic heterogeneity among individuals who develop DM. Using 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 obesity. This research applied a two-phase nested case-control study design and included metabolomic data from a total of 2,258 participants. (Research activities are ongoing.)

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.

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: 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.

Xiao-Ou Shu
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, 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.

Danxia Yu
Funding Agency:  NHLBI
R21HL140375 

We conducted an international consortium-based analysis of circulating TMAO and related metabolites in relation to dietary intakes and cardiometabolic biomarkers. A total of 17 cohort studies from the US, Europe, and Asia participated in this pooling project.

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.

Douglas C Heimburger, MD, MS Muktar Aliyu, MBBS, DrPH
Funding Agency: NIH
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.