A multidisciplinary team led by investigators at Vanderbilt University Medical Center has received a $4.2 million grant from the National Cancer Institute (NCI) to probe the genetics of colorectal adenomas — polyps that can develop into colon cancer — and to identify drug candidates that could reduce adenoma recurrence. 

Colorectal cancer is the second most common cause of cancer-related death in the United States, according to the NCI, part of the National Institutes of Health. Removing precancerous polyps during colonoscopy procedures significantly reduces the burden of colorectal cancer, but about 30% of patients who have a colorectal adenoma removed will develop recurrent adenomas. 

“Patients who have recurrent adenomas are at higher risk for developing cancer,” said Xingyi Guo, PhD, associate professor of Medicine in the Division of Epidemiology and lead principal investigator for the project. “We will integrate cutting-edge genomic research with real-world patient data from electronic health records, with the goal of translating genetic discoveries into actionable strategies to prevent colorectal cancer.” 

Zhijun Yin, PhD, MS, associate professor of Biomedical Informatics, is co-principal investigator for the four-year project. 

The team previously conducted genome-wide association studies (GWAS) of about 8,000 colorectal adenoma cases from European American and African American participants included in BioVU, VUMC’s de-identified DNA biobank and linked electronic health records. Using a large-scale analysis of electronic health records and pathology reports, the investigators also established the Vanderbilt Colonoscopy Cohort of colorectal adenoma cases after polyp removal, which includes 76,664 cases. 

With the new funding support, the team will extend its efforts to establish the largest-ever genetic study of colorectal adenoma, drawing on BioVU, the Mass General Brigham Biobank, and the NIH All of Us Research Program to include over 25,000 cases in European Americans and 6,500 cases in African Americans, with thousands of recurrences. African Americans are about 20% more likely to have colorectal cancer and about 40% more likely to die from it compared to other racial groups, according to the American Cancer Society. 

“Our approach will allow us to examine racial differences in adenoma recurrence and colorectal cancer risk,” Guo said. 

In addition to GWAS, the team will conduct transcriptome-wide, methylome-wide, and proteome-wide association studies to identify genes and proteins associated with colorectal adenomas and their recurrence. The investigators will integrate findings from these “omics” studies with electronic health record data from the Vanderbilt Colonoscopy Cohort and the Mass General Brigham Colonoscopy Cohort and use machine learning frameworks to identify candidate drugs that could prevent colorectal adenoma recurrence. They will test the most promising drug candidates in colorectal adenoma and cancer cells, patient-derived organoids, and animal models. 

“This project is an innovative integration of multiomics analyses with electronic health record-based real-world clinical evidence,” Yin said. “We anticipate that our findings will inform personalized colorectal polyp surveillance, guide therapeutic prevention strategies, and ultimately reduce the burden of colorectal cancer nationwide.” 

Guo holds a secondary appointment in the Department of Biomedical Informatics at VUMC, and Yin holds secondary appointments in the Department of Computer Science and the Department of Electrical and Computer Engineering at Vanderbilt University. Guo and Yin have both received NCI R37 MERIT Awards, which provide long-term grant support to outstanding investigators. 

Other collaborators for the new NCI grant (R01CA297582) include VUMC Department of Medicine investigators Wei Zheng, MD, PhD, MPH, Qiuyin Cai, MD, PhD, and Wanqing Wen, MD, MPH, Division of Epidemiology; Bhuminder Singh, PhD, Division of Gastroenterology, Hepatology and Nutrition; and Kristen Ciombor, MD, MSCI, Division of Hematology and Oncology; and Harvard T.H. Chan School of Public Health investigator Mingyang Song, ScD, Departments of Epidemiology and Nutrition.

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Plant-based diets have become popular for their health and environmental benefits. 

However, these benefits may vary based on the quality of the plant foods and other foods that make up the diet. A recent study at VUMC analyzed the association of plant-based diet patterns with mortality in over 77,000 mostly Black and low-income participants in the Southern Community Cohort Study, which started in 2002.  

Dietary intakes were assessed using a validated, 89-item food frequency questionnaire. The investigators generated three measures to assess the association of diet and risk of premature death: an overall plant-based diet index (PDI) that included both healthy plant foods (such as whole grains, fruits and vegetables) and unhealthy plant foods (such as fruit juices, refined grains and potatoes); a healthy plant-based diet index (hPDI); and an unhealthy plant-based diet index (uPDI).  

The study follow-up was through 2022 with a median duration of almost 17 years. The investigators identified over 26,000 deaths during the duration of the study. The highest PDI and hPDI scores were associated with reduced mortality; while the highest uPDI scores were associated with elevated mortality. 

The findings were reported in the The American Journal of Clinical Nutrition, a journal of the American Society for Nutrition. They show a strong association between high quality plant-based diets and reduced mortality rate among low-income populations, suggesting that efforts to promote diets high in healthy plant foods and low in animal foods could improve health outcomes. 

Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine and director of the Vanderbilt Epidemiology Center, is the corresponding author of the study. Fangcheng Yuan, a graduate student in the PhD Program in Epidemiology, is the first author. 

This work was supported by the National Cancer Institute, part of the National Institutes of Health (grant U01CA202979).

Guillermo Sanchez, PhD, is a staff scientist in the lab of Nick Zachos, PhD, associate professor of Surgery and Cell and Developmental Biology at Vanderbilt University.

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Walking fast for just 15 minutes per day reduced the risk of death in a large study group of mostly low-income participants. 

The research findings, published July 29 in the American Journal of Preventive Medicine, support promoting brisk walking as a strategy for improving health outcomes in all communities. 

Although the health benefits of walking are widely recognized, there has been limited research on the effect of factors such as walking pace on mortality, particularly in low-income and Black populations, said the study’s senior author, Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine and director of the Vanderbilt Epidemiology Center. 

“This is one of the few studies to quantify the effect of daily walking on mortality in a low-income and predominantly Black U.S. population,” said Zheng, who also directs the Division of Epidemiology at Vanderbilt University Medical Center. “By demonstrating the benefits of fast walking — which is a low-cost and largely accessible activity — we provide direct evidence to inform targeted public health interventions and policies to improve health outcomes.” 

The study analyzed data from the Southern Community Cohort Study (SCCS), which enrolled about 85,000 participants ages 40-79 between 2002 and 2009. Most participants (86%) were recruited in collaboration with community health centers serving low-income populations across 12 southeastern states. Participants provided baseline information, including daily walking pace and time, demographic and lifestyle factors, and medical history, using structured questionnaires. 

The current study, led by first author Lili Liu, PhD, MPH, included data from 79,856 of the SCCS participants (racial groups: 66% Black, 30% white, 4% other). In the baseline survey, participants reported the average amount of time per day (in minutes) they typically spend “walking slowly (such as moving around, walking at work, walking the dog or engaging in light exercise)” and “walking fast (such as climbing stairs, brisk walking or exercising).”

The cohort was linked to the National Death Index to obtain vital status and cause of death information through Dec. 31, 2022. Over a median follow-up of 16.7 years, 26,862 deaths occurred. 

The researchers found that fast walking as little as 15 minutes per day was associated with a nearly 20% reduction in total mortality. Slow walking more than three hours per day was associated with a smaller reduction in mortality. The benefit of fast walking remained strong even after accounting for other lifestyle factors, such as leisure-time physical activity levels. 

In addition to reducing premature death from all causes, fast walking reduced death specifically from cardiovascular diseases — the No. 1 cause of death in the United States. The researchers suggested that fast walking might reduce cardiovascular mortality by improving the heart’s efficiency and output, and by reducing the prevalence of obesity and its associated cardiovascular risks such as hypertension and high cholesterol. 

“Brisk walking offers a convenient, accessible and low-impact activity that individuals of all ages and fitness levels can use to improve general health and cardiovascular health specifically,” Zheng said. 

The authors acknowledge that self-reported data on daily walking may have included other types of physical activity, which could introduce misclassification errors. Also, the physical activity data was only collected at baseline, so changes over time could not be considered. The study’s long follow-up and large sample size contribute to “robust and reliable estimates,” they noted. 

Other VUMC co-authors are Guochang Jia, PhD, Martha Shrubsole, PhD, Wanqing Wen, MD, MPH, and Staci Sudenga, PhD. The research was supported in part by the National Institutes of Health (grant U01CA202979).

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