Cancer epidemiology cohorts (CECs) provide key insights into genetic, environmental, lifestyle, and clinical factors influencing cancer development, progression, and outcomes. Engaging communities impacted by research and participants in cohort studies is essential for building trust and ensuring the success of these studies. While the concept of engagement in cancer research is not new, the practice of engagement is evolving towards more rigorous, bidirectional relationships between researchers and communities. Here, we discuss some goals of engagement in CECs supported by the National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, which include: (i) involving community and participant voices in study design and implementation, (ii) providing updates on study progress, (iii) returning value to communities and participants, and (iv) demonstrating appreciation to study participants. This paper also outlines opportunities to enhance engagement activities across cohorts such as expanding the use of digital technologies, continuing to share lessons learned, and supporting report back of findings. Additionally, strengthening evidence base on how to engage communities at all stages of research can foster more meaningful partnerships and ultimately lead to more impactful research and better health outcomes.

Many complex disorders are impacted by the interplay of genetic and environmental factors. In gene-environment interactions (GxE), an individual's genetic and epigenetic makeup impacts the response to environmental exposures. Understanding GxE can impact health at the individual, community, and population levels. The rapid expansion of GxE research in biomedical studies for complex diseases raises many unique ethical, legal, and social implications (ELSIs) that have not been extensively explored and addressed. This review article builds on discussions originating from a workshop held by the National Institute of Environmental Health Sciences (NIEHS) and the National Human Genome Research Institute (NHGRI) in January 2022, entitled: "Ethical, Legal, and Social Implications of Gene-Environment Interaction Research." We expand upon multiple key themes to inform broad recommendations and general guidance for addressing some of the most unique and challenging ELSI in GxE research. Key takeaways include strategies and approaches for establishing sustainable community partnerships, incorporating social determinants of health and environmental justice considerations into GxE research, effectively communicating and translating GxE findings, and addressing privacy and discrimination concerns in all GxE research going forward. Additional guidelines, resources, approaches, training, and capacity building are required to further support innovative GxE research and multidisciplinary GxE research teams.

Supplementary Figure 4 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis

Supplementary Figure 5 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis

Supplementary Figure Legends from Quantitative Detection of p53 Mutations in Plasma DNA from Tobacco Smokers

Abstract Inflammation influences the development of cancer. The nitric oxide synthase (NOS2) is induced by inflammatory cytokines, e.g., tumor necrosis factor α and interleukin 1β, and produces nitric oxide (NO·), a critical mediator of the inflammatory response. Because p53 governs NO· production by transcriptionally transrepressing NOS2, we used a genetic strategy to determine whether NO· and p53 cooperatively regulate tumorigenesis. Lymphomas developed more rapidly in p53−/−NOS2−/− or p53−/−NOS2+/− mice than in p53−/−NOS2+/+ mice that were cross-bred into a >95% C57BL6 background and maintained in a pathogen-free condition. Likewise, sarcomas and lymphomas developed faster in p53+/−NOS2−/− or p53+/−NOS2+/− than in p53+/−NOS2+/+ mice. When compared with the double knockout mice, p53−/−NOS2+/+ mice showed a higher apoptotic index and a decreased proliferation index with an increased expression of death receptor ligands, CD95-L and tumor necrosis factor-related apoptosis-inducing ligand, and the cell cycle checkpoint protein, p21waf1, in the spleen and thymus before tumor development. Furthermore, mice deficient in both p53 and NOS2 produced a high level of anti-inflammatory interleukin 10 when compared with p53-deficient mice. These studies provide genetic and mechanistic evidence that NO· can suppress tumorigenesis.

Supplementary Figure 3 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis

Supplementary Figure 2 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis

Supplementary Figure 9 from Nitric Oxide Is a Key Component in Inflammation-Accelerated Tumorigenesis

Supplementary Figure 8 from Nitric Oxide Is a Key Component in Inflammation-Accelerated Tumorigenesis

Supplementary Figure 6 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis

Supplementary Figures 1-3 from Quantitative Detection of p53 Mutations in Plasma DNA from Tobacco Smokers

Supplementary Table S3. Association between serum cytokine levels and lung cancer among European Americans in PLCO study

Supplementary Figure 7 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis

Supplementary Table S5. Association between serum cytokine levels and lung cancer in WSU and PLCO studies, after adjusting for potential confounding

Supplementary Figure 7 from Nitric Oxide Is a Key Component in Inflammation-Accelerated Tumorigenesis

Supplementary Figure 1 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis

Supplementary Table 1 from Quantitative Detection of p53 Mutations in Plasma DNA from Tobacco Smokers

Supplementary Table S1. Concordance between blinded, randomized duplicates and average serum cytokine limits of detection

Supplementary Figure 8 from Nitric Oxide, a Mediator of Inflammation, Suppresses Tumorigenesis