Key Dates

Related Announcements

• December 15, 2023 - Cancer Prevention and Control Clinical Trials Grant Program (R01 Clinical Trial Required).  See NOFO PAR-24-072.
• December 05, 2022 - NCI Small Grants Program for Cancer Research for Years 2023, 2024, and 2025 (NCI Omnibus) (R03 Clinical Trial Optional). See NOFO PAR-23-058.
• September 10, 2022 - NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional). See  See NOFO PAR-22-216.
• May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185

Issued by

National Cancer Institute (NCI)

Purpose

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.

Background

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 indirectly measured 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). While fewer candidates undergo the rigorous testing needed to establish a connection with cancer processes, Presently, multi-omics platforms are facilitating 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 are under interrogated. For example, in a 28-day randomized crossover human feeding intervention, proteomic data identified dietary influences on known cancer pathway biomarkers contributing to increased risk for chronic disease, including colorectal, breast, and pancreatic cancers. A unique O-glycosylated plasma protein could distinguish between high-body-fat mass participants consuming pro-adipogenic high-glycemic load diets (high sugar and refined grains) and low-body-fat mass participants consuming low-glycemic load diets (fruits, vegetables, whole grains). These glycoproteins exclusively over-represented 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. 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). While fewer candidates undergo rigorous testing needed to establish a connection with cancer processes. Presently, multi-omics platforms are facilitating 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-report dietary intake and/or physical activity tools. Yet, most identified potential lifestyle biomarkers are un-interrogated. For example, in a 28-day randomized crossover human feeding intervention, proteomic data identified dietary influences on known cancer pathway biomarkers contributing to increased risk for chronic disease, including colorectal, breast, and pancreas cancers. A unique O-glycosylated plasma proteins could distinguish between 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 over-represented 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 individuals and across people groups. Physical activity induces biologically based outcome 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 BMI, 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 interrogated further. These data suggest additional studies may fill critical knowledge gaps in how lifestyle interventions might influence strategies for reducing cancer. Research Objectives

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:

• Rigorous pilot studies using potential baseline and recovery biomarkers of dietary intake or nutritional status on early neoplastic changes in average-risk and high-risk people groups (e.g., Lynch Syndrome carriers).
• Rigorous omics-based studies assessing how dietary intake, nutritional status, and/or physical activity modifications influence cellular or systemic functional changes (e.g., breast, colorectum, liver, lung) modifying cancer risk or its interception in humans or animal cancer models.
• Rigorous studies assessing how physical activity changes baseline and/or recovery biomarkers influencing changes in cancer processes are modifying cancer risk in humans or animal cancer models.
• Rigorous omics-based studies interrogating identified physical activity biomarkers or panels for assessing physical activity duration and intensity interventions on modifying hyperplastic events in humans or animal cancer models.

Responsive and Non-responsive Studies

Examples of responsive studies could include, but are not limited to:  

• Studies proposing novel technologies (e.g., in blood, urine) for assessing dietary intake, overall nutritional status, and/or physical activity in healthy groups compared to high-risk groups.
• Studies developing dietary biomarkers (in order of preference: recovery, predictive, or concentration) reflect how changing dietary habits or patterns may modify cancer risk in average- or high-risk groups.
• Studies developing multi-omics techniques assessing dietary intake, nutritional status, and/or physical activity as complementary exposures for preventing or intercepting cancer.
• (Non-) invasive physical activity intervention studies assessing genetically appropriate metabolite panels of cellular changes impacting cancer risk in average- or high-risk groups.

Examples of nonresponsive studies could include but are not limited to:

• Studies lacking identified baseline or recovery dietary, nutritional status, and/or physical activity biomarker candidate(s).
• Studies lacking a primary endpoint(s) related to cancer prevention or cancer interception. 
• Studies in humans lacking the clinically appropriate multidisciplinary teams (e.g., physicians, dietitians, nurses, exercise physiologists, and/or laboratory medicine/pathologists).
• Epidemiological studies associating or linking a dietary pattern with a particular cancer process or cancer outcome.

Application and Submission Information

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:
 

All instructions in the SF424 (R&R) Application Guide  and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include "NOT-CA-24-060" (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

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