The purpose of this Notice of Special Interest (NOSI) is to inform potential applicants to the National Cancer Institute (NCI) of special interest to promote research that incorporates biological information within population-based cancer epidemiologic studies to identify and understand how the interplay between environmental exposures (e.g., chemical and physical exposures, dietary, and other exposures) and germline genetic variation contribute to cancer risk. Biological information can include functional annotations of the genome (e.g., methylation, promoters or enhancers); methods of linking variants to genes (e.g., expression quantitative trait loci analysis), gene pathway or network-based approaches (e.g., network modeling); analysis of metabolites or biomarkers, or data from mechanistic studies.

Background

Although it is well accepted that both environmental and genetic factors contribute to cancer etiology, efforts to better understand how the effects of exposures vary across genotypes (and vice versa) have been less successful; measuring and quantifying environmental exposures is challenging, most genetic variants have small effects and are thus difficult to identify, and the biological consequences of most genetic variants are not well understood and are difficult to characterize. Incorporating biological information can improve power for identifying interactions among environmental exposures and genetic variants that impact disease by focusing the search to genomic regions most likely to have a functional effect. A better understanding of the functional/biological consequences (e.g., markers of oxidative damage, metabolomic markers) of an exposure can improve our ability to measure and quantify environmental exposures. Once exposures and genetic variants have been hypothesized to affect cancer susceptibility, laboratory approaches can be used to understand the biological mechanisms by which exposures and genetics affect cancer risk. This research could help identify subgroups with varying degrees of susceptibility to environmental exposures.

Research Objectives

NCI is interested in research that integrates biological data with epidemiological data from environmental exposure and germline genetic projects, and encourages applications that include mechanistic follow-up (e.g., appropriate laboratory experiments that go beyond annotation) designed to understand the biological processes involved in the interplay between environmental exposures and genes at the molecular, cellular, and/or organismal level. Studies of cancer risk are of interest for this Notice.

This NOSI encourages, but is not limited to, research applications in the following areas:

• Epidemiological studies and statistical approaches that incorporate biological data to discover, verify, and prioritize exposure and genetic associations for functional follow-up

• Integration of biological information from experimental or human studies with environmental exposure and germline genetics data to inform and improve exposure assessment and/or describe how environmental exposures and genetics contribute to cancer risk
• Use of high-throughput model systems or in vitro studies to identify and characterize biological mechanisms underlying the interplay between environmental exposures and germline genetic variants

• Risk stratification studies to identify genotypes that may confer a higher risk of cancer in conjunction with specific environmental exposures and corresponding deleterious biological responses

Application and Submission Information

This NOSI applies to Application Due Dates on or after February 5, 2020, and subsequent receipt dates through January 08, 2022.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these FOAs through the expiration date of this Notice.

Activity Code	FOA	Application Due Date	Expiration Date
R01	PA-18-529, Early-life Factors and Cancer Development Later in Life (R01 Clinical Trial Not Allowed)	February 5, 2020	January 8, 2021
R03	PA-18-531, Early-life Factors and Cancer Development Later in Life (R03 Clinical Trial Not Allowed)	February 16, 2020	January 8, 2021
R21	PA-18-532, Early-life Factors and Cancer Development Later in Life (R21 Clinical Trial Not Allowed)	February 16, 2020	January 8, 2021
R01	PA-18-677, Epidemiologic Research on Emerging Risk Factors and Liver Cancer Susceptibility (R01 Clinical Trial Not Allowed)	June 5, 2020	May 8, 2021
R21	PA-18-678, Epidemiologic Research on Emerging Risk Factors and Liver Cancer Susceptibility (R21 Clinical Trial Not Allowed)	June 16, 2020	May 8, 2021
R01	PA-19-056, NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)	January 5, 2020	January 8, 2022
R01	PAR-18-869, Modular R01s in Cancer Control and Population Sciences (R01 Clinical Trial Optional)	March 6, 2020	March 9, 2021
R01	PAR-19-018, Mechanisms of Disparities in Etiology and Outcomes of Lung Cancer in the US: The Role of Risk and Protective Factors (R01 Clinical Trial Not Allowed)	March 4, 2020	March 5, 2021
R21	PAR-19-019, Mechanisms of Disparities in Etiology and Outcomes of Lung Cancer in the US: The Role of Risk and Protective Factors (R21 Clinical Trial Not Allowed)	March 4, 2020	March 5, 2021

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-20-002" (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 be not be considered for the NOSI initiative.