July 30, 2024
National Cancer Institute (NCI)
This Notice of Special Interest (NOSI) is to support applications improving diet and/or physical activity assessment biomarker development for evaluating lifestyle-based cancer prevention and interception approaches across diverse settings. Multiple Principal Investigator structured applications with the appropriate expertise are encouraged to apply. Preclinical and pilot human studies assessing baseline and recovery biomarkers for dietary intake, nutritional status, and/or physical activity intervention(s) as complementary exposures are important for early cancer prevention and its interception in high-risk individuals or groups.
Please note that this NOSI replaces NOT-CA-24-060, published on June 12, 2024.
Diet and physical activity are multidimensional exposures influencing cancer prevention and its interception. Lifestyle approaches are safe, long-term approaches used globally to reduce some obesity-related cancer risks (e.g., post-menopausal breast, colorectal, pancreatic, multiple myeloma, and liver cancers) while promoting overall health and well-being. Complex physiological interactions occur daily between ingested foods, physical activity, and the host's general nutritional status, influencing their cancer risk. Evidence from the European Prospective Investigation into Cancer and Nutrition (EPIC) Spain cohort concluded that poor diet and nutritional status, low physical activity, excess body weight, and alcohol intake are modifiable lifestyle factors promoting metabolic dysfunction and contributing to chronic disease initiation, including obesity and some cancers. Diet and physical activity are indirect measurements as validated direct exposure biomarkers are missing. Current gaps in our scientific understanding exist about how lifestyle risk factors modify cancer risks across average- and high-risk groups. Developing direct baseline and exposure biomarkers indicative of changing cancer risk is critical for establishing safe, long-term lifestyle interventions for preventing and intercepting cancer in average- and high-risk groups.
Developing direct dietary intake and/or nutritional status biomarkers.
Few objective baseline status and recovery biomarkers exist for basic nutritional assessment (e.g., doubly labeled water for energy, 24-hour urinary nitrogen, 24-hour urinary sucrose). Even fewer candidate biomarkers undergo the rigorous testing needed to establish their connection(s) with cancer processes. Yet, multi-omics platforms can facilitate biomarker advances across biomedical disciplines. High-throughput analytical chemistry techniques (e.g., mass spectroscopy, nuclear magnetic resonance) are easy-to-use, robust improvements over widely used self-reported dietary intake and/or physical activity tools. Yet, most identified potential lifestyle biomarkers lack further interrogation. For example, in a 28-day randomized crossover human feeding intervention, proteomic data identified dietary influences on known cancer pathway biomarkers for colorectal, breast, and pancreatic cancers. One such potential biomarker identified is a unique O-glycosylated plasma protein that can distinguish high-body-fat mass participants consuming pro-adipogenic high-glycemic load diets (high sugar and refined grains) from low-body-fat mass participants consuming low-glycemic load diets (fruits, vegetables, whole grains). These glycoproteins exclusively overrepresented changes in the cell cycle, DNA repair, and DNA replication pathways implicated in cancer initiation. Interestingly, posttranslational protein modified pathway plasma biomarkers were detected in many cancer types and were similarly found in participants consuming high glycemic load diets, irrespective of personal fat mass. These data suggest dietary biomarkers may reflect biological responses signaling early changes in cancer-related pathways, distinguishing high-risk individuals based on diet and individual body fat mass composition, warranting further exploration.
Developing direct physical activity biomarkers.
Similar gaps exist in directly evaluating physical activity response differences between free-living high-risk measurements (e.g., muscle mass, fat mass, and cardiovascular capacity) as well as short-term metabolic changes in energy expenditure. Yet, validation studies of free-living individuals required to assess potential physical activity response differences are missing. Exercise physiologists routinely use oxidative stress, inflammation, and muscle damage biomarkers to suggest health status, but data are limited to younger athletes. Compelling evidence from the American College of Sports Medicine Roundtable Report (2019) shows physical activity has beneficial effects on modifying risks for several cancers, but it is unknown what type, amount, intensity, and timing of physical activity is required to influence cancer risk. Additional evidence shows physical activity influences host metabolic controls. Using over 2,900 replication samples to confirm non-targeted mass spectroscopy metabolites previously identified in the UK Airwave Health Monitoring Study, investigators reported vigorous physical activity enhanced arginine and proline amino acid metabolism, accompanied by mitochondrial electron transport chain changes by 1.5- and 2.0-fold, respectively. When data were adjusted for age, sex, and body mass index, 2 of 36 identified metabolites had nominally significant IVW estimates, specifically 3-(4-hydroxy-phenyl) lactate and alpha-hydroxy isovalerate. Additionally, 1-(1-enyl-stearyl)-2-docosahexaenoyl-GPC (P-18:0/22:6) was identified when adjusted for genetic differences, but none were further interrogated. These data suggest additional studies may fill critical knowledge gaps in how lifestyle interventions might influence strategies for reducing cancer.
This NOSI will serve as an important advancement in first-line diet and physical activity lifestyle interventions for reducing cancer risks in healthy and at-risk individuals and groups (e.g., obesity-related cancers). Through this NOSI, NCI DCP is particularly interested in studies developing and evaluating rigorous diet and/or physical activity baseline and recovery biomarker studies for use in long-term cancer risk reduction and its interception studies in high-risk groups across the lifecycle. This NOSI will support, but is not limited to, the following research areas:
Examples of responsive studies include, but are not limited to:
Examples of nonresponsive studies could include, but are not limited to:
This Notice applies to due dates on or after October 5, 2024, and subsequent application due dates through January 08, 2027 (the expiration date for this NOSI).
Applicants are strongly advised to review the specific Application Due Date Table for each NOFO (listed below) before applying to this NOSI.
Submit applications for this initiative using one of the following notices of funding opportunity (NOFOs) or any reissues of these announcements through the expiration date of this NOSI. Please note that each NOFO has a specific Expiration Date:
NOFO Number | Title of NOFO | First Available Due Date |
PAR-24-072 | Cancer Prevention and Control Clinical Trials Grant Program (R01 Clinical Trial Required) | October 05, 2024 |
PAR-23-058 | NCI Small Grants Program for Cancer Research for Years 2023, 2024, and 2025 (NCI Omnibus) (R03 Clinical Trial Optional) | October 17, 2024 |
PAR-22-216 | NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional) | October 10, 2024 |
PA-20-185 | NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) | October 05, 2024 |
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.
Scientific Research Contact(s)
For all inquiries related to this NOSI:
Nancy Emenaker, PhD, MEd, RDN, LD, FAND
National Cancer Institute (NCI)
Telephone: 240-276-7125
Email: nancy.emenaker@nih.gov
Financial/Grants Management Contact(s)
Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov