Design of a mindfulness intervention to reduce risk factors for colorectal cancer among at-risk Black women in Chicago

Abstract

Chronic stress can directly and indirectly promote carcinogenesis through immune, metabolic, and microbial pathways. Our overarching hypothesis is that reducing chronic stress will have important implications for colorectal cancer (CRC) risk reduction among vulnerable and high-risk populations. A promising approach for reducing chronic stress is mindfulness. Mindfulness is a meditation-based technique that achieves a state of mind that is used to experience higher awareness or consciousness. Existing small studies suggest mindfulness can positively regulate stress response in a way that translates to anticancer effects, including reduced systemic inflammation. We propose to evaluate an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. At baseline and postintervention, participants will provide blood, hair, and stool; undergo body composition analysis; and complete mood and lifestyle-related surveys. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota—risk markers and risk pathways associated with CRC. The data generated through this project will inform if mindfulness is a feasible option for CRC risk reduction among high-risk individuals.

NEW & NOTEWORTHY We propose to evaluate an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota—risk markers and risk pathways associated with CRC.

INTRODUCTION

Black Americans have among the highest colorectal cancer (CRC) incidence and mortality for reasons that are not fully elucidated but are known to exceed the impact of screening and early detection differences (1). Both biological and environmental exposures play a significant role in colorectal carcinogenesis, which develops through a multistep mutational process (2). Socioenvironmental stressors are widely regarded as important drivers of cancer health inequities. Vulnerable communities are communities facing multiple intersecting challenges. Some examples can include, but are not limited to, the presence of violent crime, geographic isolation or limited access to healthcare facilities, inadequate insurance coverage or ability to afford health treatments, and socioeconomic deprivation (3). Compared with other racial and ethnic groups, Black Americans are more likely to live in urban areas that are considered vulnerable communities. Chronic exposure to violence and fear of violence, together with socioeconomic stressors, can elicit a sustained stress response with downstream effects linked to carcinogenesis (4). Specifically, chronic stress can dysregulate the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis in a manner that promotes cancer through hormonal (5), immune (6, 7), metabolic (8), and microbial pathways (9, 10).

Anecdotal evidence linking chronic stress and cancer goes back almost two millennia, with early reports describing that cancer was less likely to occur in persons with better mental well-being (11). Studies suggest that Black women may be excessively burdened by the physiological impacts of chronic stress stemming from an array of personal and social factors (12). Chronic stress dysregulates and augments the release of mediators of the neuroendocrine stress response system, including SNS-related catecholamines, epinephrine (EPI) and norepinephrine (NE), and HPA axis-related hormones, including cortisol (CORT) (5, 11). Animal studies have connected stress-related increases in EPI, NE, and CORT to cancer initiation (11, 13). CORT can affect cell cycle control and reduce DNA repair processes to promote carcinogenesis (11).

In response to stress, NE and EPI potentiate their effect on adrenergic receptors (ARs). Chronic activation of β-adrenergic receptors (β-ARs) specifically has been implicated in carcinogenesis with their activation linked to inflammation, proliferative signaling, genome instability, and immune evasion (11, 14–16). Colon cancer cells express β-ARs, and their activation has been linked to cancer initiation and tumor progression (14). In a human colon cancer cell line, β-AR antagonist drugs used to treat cardiovascular disease significantly reduced cell proliferation in treated cells in the presence of an AR agonist (14). Epidemiological and clinical evidence also links β-AR antagonist drug use to reduced cancer risk, including CRC, and lower cancer mortality (17, 18). These studies provided strong evidence of the molecular mechanisms at the intersection between chronic stress and cancer. However, the epidemiological evidence directly linking chronic stress to cancer is mixed and fraught with limitations, including failure to assess objective markers of stress, with investigators relying largely on self-report measures. Moreover, the existing literature has focused largely on White and higher-income individuals instead of the most vulnerable populations as it relates to both chronic stress and cancer (16).

Despite these limitations, there is strong evidence regarding the deleterious indirect effects of chronic stress and overexpressed NE, EPI, and CORT on impaired glucose metabolism (8), increased overall and central adiposity (19), increased inflammation (20), and gut microbiome dysbiosis (21)—known drivers of colorectal carcinogenesis (22, 23). Given the totality of the evidence, reducing chronic stress and augmenting chronic exposure to NE, EPI, and CORT is a plausible approach to CRC risk reduction that remains grossly understudied.

One promising approach to reducing chronic stress is mindfulness. Mindfulness is a meditation-based technique to achieve a state of mind to experience higher awareness or consciousness and may include spirituality or religion (24, 25). Studies indicate that mindfulness is desirable among Black populations if they receive tailored mindfulness interventions for Black adults (26–28). Several small studies suggest that short-term (∼8 wk) exposure to mindfulness can lower perceived stress (29), CORT, and resting heart rate (30–32). Existing evidence also suggests that short-term mindfulness yields positive effects specific to body weight (33), glucose metabolism (34), and inflammation (35), which are known risk drivers of CRC (36). Mindfulness’s effect on the gut microbiome has not been reported, although a few ongoing studies will undoubtedly add to this knowledge base (37). Mindfulness has been studied in the context of cancer care and among cancer survivors, with positive effects on perceived stress, circulating CORT, and proinflammatory cytokines (38–41). However, there is a gap in prospective trials examining the utility of mindfulness for cancer risk reduction, particularly among Black women.

This article describes the design of an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. The main objective is to assess the feasibility and acceptability of the intervention. Secondary objectives include exploring changes in stress markers (both subjective and objective), body composition, fasting glucose, systemic inflammatory markers, and gut microbiota from baseline to postintervention.

METHODS

The University of Illinois Chicago (IRB No. 2023-1359) approved the experimental protocol on February 20, 2024. Participants will provide written informed consent before study participation. The trial is registered at ClinicalTrials.gov (NCT06323421).

STUDY DESIGN

This is an 8-wk, single-arm feasibility pilot study (Fig. 1). Forty-eight Black women (to allow for an anticipated 20% dropout with 40 women completing the trial) aged between 45 and 65 yr, with moderate to high perceived stress [Perceived Stress Score (PSS) ≥ 14] and risk of CRC (one or more colorectal adenomas detected during direct access colonoscopy in the past 24 mo) screened from EPIC will be invited to participate in this study. PSS is a scale that contains 10 items and aims to index aspects of stress experienced within the past month. As expected, higher scores indicate higher perceived stress, with scores between 14 and 26 indicating moderate perceived stress and >27 points indicating high perceived stress (42).

Figure 1.

Study design. Created with BioRender.

Potential participants will be asked to come to our laboratory at the University of Illinois, Chicago (UIC) to confirm eligibility. After eligibility is confirmed, we will collect baseline data, which include blood, hair, and stool. We will also measure body composition, blood pressure, heart rate, height, and weight and ask participants to answer several questionnaires during the visit. We will monitor physical activity for 7 days after the baseline data collection visit. Enrolled participants will then participate in an 8-wk mindfulness intervention in a hybrid format with a therapist. Once the mindfulness intervention ends, participants will be asked to return to our laboratory at UIC for postintervention measurements. During the postintervention data collection visit, the same data collected at baseline will be measured a second time. Physical activity will be monitored during 7 days after the postintervention data collection visit.

SETTING AND RECRUITMENT

Women will be recruited from the University of Illinois Health (UI Health) Gastrointestinal Lab. Electronic health records (EHRs) will be screened (EPIC Slicer Dicer application) for potential participants who have received a direct access colonoscopy at UI Health in the past 36 mo.

PARTICIPANTS

Screening

Potentially eligible individuals will be notified about the opportunity to participate in this research via EPIC MyChart message, text message, phone, or email to assess study interest. Interested and eligible individuals will be sent a screening questionnaire link via REDCap or assessed for eligibility over the phone. The screening questionnaire will ask regarding all of the inclusion and exclusion criteria for enrollment in the study (i.e., PSS questionnaire, past medical history, fiber intake, and access to technology). Those meeting eligibility based on the survey or phone screen will be invited to an in-person screen to confirm eligibility and confirm body mass index (BMI).

Inclusion Criteria

Inclusion criteria are as follows: female based on sex assigned at birth, self-identify as Black, 45–65 yr old, have completed a colonoscopy in the past 36 mo, classify as elevated risk of CRC (one or more colorectal adenomas detected during direct access colonoscopy in the past 24 mo), have a BMI between 18.5 and 49.9 kg/m², own and use a smartphone, computer, or tablet with access to the Internet, score ≥14 on the PSS (42) at screening, and reside in a Chicago community with high violent crime (20 of 77 Chicago community areas based on data from the Chicago Health Atlas) (43).

Exclusion Criteria

Exclusion criteria are as follows: 1) history of CRC, 2) use of antibiotics (oral/IV) in the past 2 mo, 3) inflammatory bowel disease or genetic predisposition to CRC, 4) cancer diagnosis or cancer treatment in the past 12 mo, 5) >50 g of ethanol consumption/daily, 6) currently smoking cigarettes, 7) history of bariatric surgery or bowel resection, 8) immunodeficiency/autoimmune disease or uncontrolled diabetes (HbA1c >9% based on EHR), 9) fiber or pre-/probiotic supplements ≥3 days/wk, and 10) significant health conditions or take medications that impact participation or expected outcomes (e.g., β-blocker, Cushing’s syndrome).

Power and Sample Size

A total of 48 Black women will be recruited, allowing for 20% dropout, resulting in completed data collection on 40 individuals, which supports the calculation of confidence intervals for feasibility and effect size components (44). This feasibility-pilot study is not powered to detect statistically significant effects for improvement in chronic stress or the secondary/exploratory measures. The minimum detectable difference from baseline to postintervention for these outcomes is 1 SD with baseline and postmeasurements that are correlated at r = 0.5, α = 0.05, and 80% power.

Approaches to participant retention.

All participants will receive a monetary subsidy for participating in the trial. They will receive a parking voucher or $7 (cash) for travel reimbursement for each completed study or in person intervention visit. At the completion of the baseline visit, participants will receive a total of $50 (cash). At the completion of the postintervention visit, they will receive $100 (cash). So, if a participant attends both the baseline visit and the postintervention visit, they will be compensated $150 (cash). To maximize retention, we will provide financial and logistical support for transportation for the in-person data collection visits.

Intervention

All enrolled participants will complete the 8-wk mindfulness intervention. A hybrid approach will be used to increase weekly exposure to mindfulness through synchronous and asynchronous content. Jon Kabat Zinn’s Mindfulness-Based Stress Reduction Program informed the mindfulness content for both the group sessions and web-based intervention (45). The weekly synchronous and asynchronous content is described in Table 1.

Table 1.

Weekly mindfulness content provided

Week 1	Asynchronous Session 1	Begin My Journey
	Synchronous Session 1	Introduction and Overview of the My ESSENCE-CRC Program
		✔ Provide participants with ground rules and expectations of the program. Introduce instructors and group members
		✔ Introduce the concept of mind and body practices (mindfulness) and initiate meditation practice • Breathing meditation
Week 2	Asynchronous Session 2	Mindfulness-Based Care
	Synchronous Session 2	Stepping into My ESSENCE-Colorectal Cancer (CRC) Intervention Program
		✔ Introduce instructors and group members (IF new members were not available for session 1)
		✔ Continue discussion of the concept of mind and body practices (mindfulness) and initiate meditation practice
		• Sitting with breath meditation
		• Mindful sensory exercise and eating
		• Poem activity
		✔ Introduce cancer and stress connections
Week 3	Asynchronous Session 3	Focusing on Health
	Synchronous Session 3	Stepping Out of Automatic Pilot
		✔ Sitting meditation
		✔ Discuss how thoughts, emotions, and sensations are related to each other and to mind and body practices
		✔ Give a synopsis of body scan to the group
		✔ Provide participants with a rationale for the connection between developing awareness through mindfulness meditation and its potential impact on coping with stress • Discuss the sympathetic (Fight or Flight) and parasympathetic (Rest or Digest) nervous system and how your body reacts to stress in more detail • Discuss how managing stress can impact risk for CRC
Week 4	Asynchronous Session 4	Staying Healthy!
	Synchronous Session 4	Paying Attention to Stressors
		✔ Group meditation
		✔ Discuss how your body reacts to pleasant and unpleasant events
Week 5	Asynchronous Session 5	Mind Over Mood
	Synchronous Session 5	Body Movement and Mindfulness
		✔ Introduce yoga/light stretching as a mindful movement practice. It is an extension of the body scan practice and can be helpful for people who are restless
		✔ Discuss mind wandering
		✔ Provide rationale and instructions for stimulus control. Emphasize the connections with the on-going practice of awareness of stressors
Week 6	Asynchronous Session 6	Relaxation and Acceptance
	Synchronous Session 6	How Stressors Relate to Poor Health
		✔ Review of the program at half-way point and participants’ thoughts and feelings towards Mindfulness practice
		✔ Meditations to practice:
		• Movement meditation (Yoga)
		• Sitting meditation
Week 7	Asynchronous Session 7	Reflections on Body Image and Healthy Weight
	Synchronous Session 7	Acceptance and Letting Go
		✔ Sitting Meditation: Invite participants to bring in a difficult thought, emotion, or body sensation to work with during this meditation. Acknowledge that it might be difficult to sit for longer periods of time
		✔ Emphasize the principles of acceptance and letting go and the relevance to working with the principles behind how stressors relate to health
		✔ Provide participants with a short meditation that can be used to cope with stress by stepping out of automatic pilot and bringing attention to the present moment
Week 8	Asynchronous Session 8	Moving Forward
	Synchronous Session 8	Revisiting the Relationship with Stress
		✔ Engage in a Sitting Meditation with Choiceless Awareness. Invite whatever arises in the mind and body to become the focus of attention. This meditation can be led with less guidance, allowing more silence
		✔ Help participants develop an action plan to work with future episodes of stress
		✔ Closing ceremony provide a sense of closure to the program and encouragement for participants to continue in their own journey

Synchronous group sessions.

The synchronous group sessions will be held in-person (2 weekly group sessions and 1 half-day retreat) and remote (6 group sessions) and led by a race concordant PhD level psychologist with significant experience in mindfulness interventions among Black individuals (46). The in-person group sessions will be held at UIC, and the remote sessions will be held over Zoom. Sessions will be held on the same day and time each week. One in-person session will be a half-day group retreat held on a Saturday at UIC. The retreat will be silent and focus on the meditation activities reviewed during the weekly sessions. Weekly sessions will last 60–90 min, and the retreat will last ∼4 h.

Asynchronous web-based intervention.

To increase weekly exposure to mindfulness practices beyond the weekly group sessions, we adapted a web-based mindfulness intervention, My Journey, for this study (47). The web content is divided into 8 wk, with the content dovetailing with the content in the group sessions. Participants will be encouraged to engage with the web intervention for at least 30 min weekly. Details of each session are provided in Fig. 2. During the initial in-person group session, the interventionist will show participants how to access and navigate the website. The web intervention provides back-end analytics at the individual level to track usage metrics. Staff will track usage and contact participants (phone, text, email) who fail to engage with web intervention to encourage use. To allow participants to view the web-based intervention comfortably and to fully engage in the remote group sessions, headphones with a microphone will be provided.

Figure 2.

My Journey: asynchronous mindfulness weekly content.

Data Collection and Measures

Feasibility and adherence measures will be collected continuously. Other participant survey and biomarker data will be collected at baseline and postintervention unless stated otherwise.

Primary Outcomes

Feasibility, adherence, and acceptability.

Detailed records of the number of individuals eligible, approached (phone, email, EHR patient portal), screened, and the number of individuals who decline and their reason(s) for nonenrollment will be collected. Once an individual is enrolled, attendance at study visits, completeness of data, synchronous session attendance, asynchronous web intervention usage metrics, and loss to follow-up/withdrawal will be closely monitored. Regarding attendance to sessions, both binary (yes/no) metrics and the duration each participant attended each session will be tracked. To track the progress of participants through the trial, we will adhere to and update weekly the Consolidated Standards of Reporting Trials (CONSORT) participant flow diagram (48). Individuals who voluntarily withdraw will be asked to provide reason(s) for revoking their enrollment. Rates of enrollment and retention are key feasibility outcomes. Weekly group session attendance and asynchronous web intervention usage metrics are key acceptability outcomes. Participants will also complete an acceptability of intervention measure (scores range from 4 to 20 points with higher scores reflecting higher acceptability) at study midpoint and postintervention (49). These activities will allow for the assessment of success and failure points to guide future work.

The study will be deemed feasible if ≥30% of those approached enroll at a minimum rate of 1–3 women/wk and ≥80% of women enrolled are retained with complete data collection at the assessment timepoints. The intervention will be deemed acceptable if women attend ≥80% of the mindfulness group sessions, engage with ≥80% of the asynchronous mindfulness content, and score ≥16 on the acceptability survey.

Secondary Outcomes

Hair cortisol concentration.

We will assess hair cortisol concentration (HCORT) from a 2-cm hair sample (1 mo growth represents cortisol deposition over the previous month) (50, 51). Hair will be taken by the research team during the data collection appointment from the crown and vortex of the head and stored at −80°C until analysis. Hair health will also be considered when collecting hair samples. Participants will answer a questionnaire regarding hair type, usage of hair products used, and hair care routine at both timepoints. Each hair sample will be weighed, washed twice with isopropanol, and air-dried for at least 24 h. Methanol will be added to the powdered hair, and the cortisol will be extracted. Tubes are centrifuged, after which methanol extract is removed to a clean tube and evaporated using a vacuum evaporator. The dried extract is reconstituted in assay buffer, filtered to remove particulate material, and then frozen for subsequent assay. The cortisol content of the extract is analyzed in duplicate along with control via immunoassay (Enzo Lifesciences, Farmingdale, NY), which is converted to pg. cortisol/mg dry hair weight. Baseline and postintervention samples for a participant will be assayed on the same plate. Hair samples will not be collected from individuals who have recently (within 2 mo) used a corticosteroid medication.

Circulating stress-related biomarkers (CORT, EPI, NE).

A fasting (12 h) venous blood sample will be obtained and processed for plasma and serum; blood will be stored at −80°C or shipped for analysis. We will measure circulating CORT, NE, and EPI in serum via mass spectrometry at the RRC Mass Spectrometry Core (UIC, Chicago, IL). The Core will follow standard sample preparation and analysis procedures and use Sigma-Aldrich (St. Louis, MO) standards. CORT will be extracted by protein precipitation protocol, followed by dryness under nitrogen and reconstitution in HPLC-grade water acetonitrile and formic acid before being subjected to LC/MS analysis. The sample analysis will be conducted in the LC-MS/MS (Agilent 1290 UPLC coupled to AB Sciex QTRAP 6500).

Stool collection.

Participants will be instructed regarding home stool collection. The stool kit will have a prelabeled envelope. After collecting the sample, participants will mail the sample to the research team using a prelabeled envelope that will be delivered within 2 days of shipment. The research team will provide the participants with the OMNIgene-GUT tube (DNA Genotek, Ottawa, Canada) gut microbiome compositional analysis. A Bristol stool scale will also be completed by the participant (52). Upon receipt, the stool will be aliquoted, and a portion will be processed for the calprotectin assay (see below) and stored at –20°C and –80°C until analysis.

Microbial amplicon sequencing and bioinformatics processing.

16S rRNA amplicon sequencing will be performed using microbial DNA extracted from participant stool samples. Sample preparation and analysis will be conducted by the University of Illinois Genomics Core. The V4 region of the 16S rRNA gene will be amplified and sequenced with the Illumina MiniSeq platform (Azenta Life Sciences, Burlington). Environmental controls will be included in the sequences to distinguish any contaminants. 16S rRNA reads will be processed with DADA2 (53) to identify the number of amplicon sequence variants (ASVs) counts. ASVs with a low number of counts or with low abundance (<0.5%) will be removed from downstream analysis. ASVs will be summarized at different phylogenetic levels and normalized using cumulative sum scaling (54).

Colonic inflammation.

Fecal calprotectin is a noninvasive marker of intestinal inflammation (55). From stool at baseline and postintervention, fecal calprotectin will be assayed using a commercially available immunoassay kit (Bühlmann Diagnostics, Amherst, NH). The lower level of detection for this assay is 32.5 μg/g. Values below the lower limit of detection are assigned at the value of 16.25 μg/g per assay instructions. Values above 100 μg/g are suggestive of intestinal inflammation (56).

Body weight and body composition.

Body weight will be measured in a fasted state to the nearest 0.1 kg using a calibrated digital scale (Tanita BWB‐800). Body composition will be measured by dual-energy x‐ray absorptiometry (iDXA; GE Healthcare, Chicago). Height will be measured during the in-person screening only using a fixed stadiometer (Seca, Hamburg, Germany). BMI will be calculated as weight (kg)/height (m²) from screening height and measured body weights.

C-reactive protein and glucose.

High-sensitivity C-reactive protein (hs-CRP) via nephelometry and fasting glucose will be assayed from serum by a local commercial laboratory (Quest Diagnostics, Wood Dale, IL).

Resting heart rate.

Heart rate will be assessed in duplicate using an automated blood pressure cuff (Omron, Hoffman Estates, IL). Participants will rest quietly for 10 min before the first measurement, with a 5-min rest between measurements. The average of the two measures will be calculated.

Dietary intake.

Habitual dietary intake will be measured using the NCI Diet History Questionnaire-III (57, 58). Estimated intake of macro- and micronutrients as % kcal or per 1,000 kcal and diet quality using the current Healthy Eating Index (HEI) will be calculated (59).

Physical activity and sleep behavior.

Participants will receive a Fitbit during the baseline data collection visit. Participants will be asked to wear the Fitbit on their wrist for 7 days after the baseline visit and 7 days before the postintervention data collection visit. The data will be processed using the Fitabase (Small Steps Labs, LLC) software. Fitbit data aim to determine changes in physical activity and sleep behaviors during the intervention.

Other participant measures that could influence adherence and intervention outcomes.

The participant’s sociodemographic status and health history will be assessed at baseline. At all in‐person data collection visits, mental health symptoms of anxiety (Generalized Anxiety Disorder‐7) (60), stress (PSS-10) (42), depression (Patient Health Questionnaire‐8) (61), spirituality (PEW Surveys Questions Religion and Spirituality) (62), discrimination (63), childhood experiences (Adverse Childhood Experience Questionnaire) (64), resilience (Connor-Davidson Resilience Scale 25) (65), and sleep hygiene (Pittsburgh Sleep Quality Index) will be assessed (66). The data collected using these questionnaires will help identify any potential confounding factors that may impact the study’s outcomes and allow for more accurate analysis and interpretation of the results.

Data Analyses Methods

Data will be analyzed using the statistical software SAS V9.4 (SAS Institute, Cary, NC) and R. We will summarize feasibility and acceptability metrics using descriptive statistics such as frequencies, percentages, means, and standard deviations. The endpoints include recruitment rate among eligible persons approached, adherence (i.e., % attendance at sessions and interaction with asynchronous content), % retained through postintervention, and scores on the acceptability survey. Their 95% confidence intervals will be constructed assuming a binomial distribution. An exact binomial test will be conducted to determine if the estimated rate is significantly higher than the respective threshold. For the secondary outcomes, we will first evaluate distributions, identify outliers, look for missing data patterns, and determine effect size estimates. We will also examine the trend plot of each participant and summarize trends to understand patterns of change for each measure. Specific to the microbiome analysis, variation in community structure [alpha (i.e., Shannon) (67) and beta diversity (e.g., Bray–Curtis distances) (68)] in response to the intervention will be determined with the vegan (69) and phyloseq (70) packages in R (R Foundation for Statistical Computing, Vienna, Austria). Compositional changes will be determined using zero-inflated generalized linear mixed models correcting for covariates (e.g., BMI, age) using MaAsLin2 (54, 71). We will explore how the microbial and colonic inflammatory changes correspond to changes in stress levels, anthropometrics, glucose, and systemic inflammatory measures.

INNOVATION, LIMITATIONS, AND CONCLUSIONS

The proposed study demonstrates innovation as follows. 1) Hypothesis: targeting chronic stress for CRC risk factor reduction remains an understudied area in cancer health research despite the evidence indicating chronic stress promotes dysregulation of the SNS and HPA axis with downstream direct and indirect implications for cancer (72). Given the untoward chronic stress experienced by many Americans with a preponderance of exposure among Black Americans, studying chronic stress as a target for CRC risk factor reduction is innovative and warranted and could be an important step toward cancer health equity. 2) Delivery: the mindfulness intervention will be implemented in a hybrid format with both groups synchronous and asynchronous, and remote content. This approach to intervention delivery maintains the fidelity of mindfulness (live group sessions with an initial session in person) but holds potential for low-cost integration into healthcare systems and for wide dissemination. 3) Comprehensive and robust assessment of stress response: we will assess biomarkers related to the SNS and HPA axis, including circulating NE, EPI, and CORT and HCORT. 4) Comprehensive and feasible exploration of mindfulness’s effect on anthropometric, metabolic, immune, and microbial endpoints links chronic stress to CRC.

Although the project has innovations, there are also identified challenges and limitations. Physical activity will be monitored at baseline and postintervention, but no physical activity intervention will be implemented. In addition, we have not added any inclusion/exclusion criteria linked to physical activity. This was done with the aim of enhancing the generalizability of the sample. We understand the impact of exercise on mental health; however, due to this being a pilot study, we were unable to include it at this time. It is possible that assembling a group of people at the same time each week for 8 wk may pose a challenge. If this is the case, we will offer more than one session weekly to accommodate all participants. Given the diurnal variations of the stress-related markers, it is critical to assess individuals at the same time of day. Moreover, the stress-related markers could be influenced by a recent traumatic event. To support the rigor of our biospecimen sampling approach, stress markers will be assessed the same time of day at baseline and postintervention for each participant, and a recent traumatic events survey will be administered to allow for robust interpretation of the data. Although the study includes a relatively comprehensive examination of the mechanistic underpinnings of the stress and CRC relationship, there are certainly other pathways that could be investigated. For example, chronic stress can interfere with sex hormone metabolism (i.e., suppressed gonadotropin releasing hormone), which is associated with an increased risk of CRC (73). Chronic stress can also suppress T-cell function, which would promote carcinogenesis (74). Moreover, gut microbes harbor enzymes capable of metabolizing cortisol to an isoform with a similar structure and function as testosterone (75). Androgens and notably testosterone are implicated in colon tumorigenesis, providing a plausible hypothesis, linking chronic stress, the gut microbiome, and CRC (76).

In conclusion, Black Americans exhibit among the highest CRC incidence and mortality for reasons that are poorly understood. Many community areas in Chicago and the United States experience chronic stressors, including economic deprivation and violent crime—with Black communities disproportionately burdened. There is mounting evidence that chronic stress can promote carcinogenesis. A promising approach for reducing stress is mindfulness. This study will pilot a mindfulness intervention to determine if mitigating chronic stress is a formidable target for CRC prevention among a vulnerable population of Black women in the Chicago area.

GRANTS

This work was supported by T32CA057699 (to Manoela Lima Oliveira) and U54CA202997, U54CA203000, and U54CA202995 (to Alana Biggers, Lisa Marie Tussing‐Humphreys, Keith B. Naylor, Zhengjia Chen, Betina Yanez, Emily Booms).

DISCLAIMERS

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

N.S.L., A.E., D.B., S.N., K.B.N., B.Y., and L.M.T.-H. conceived and designed research; N.S.L., A.H., J.S., L.M.T.-H. performed experiments; Z.C. and L.M.T.-H. analyzed data; J.S. and L.M.T.-H. interpreted results of experiments; M.L.O. and L.M.T.-H. prepared figures; M.L.O., N.S.L., and L.M.T.-H. and drafted manuscript; M.L.O., N.S.L., G.K.R., A.H., E.B., and L.M.T.-H. edited and revised manuscript; M.L.O., N.S.L., G.K.R., A.E., A.H., B.Y., E.B., and L.M.T.-H. approved final version of manuscript.