BACKGROUND:The impact of physical activity in patients with cancer treated with immune checkpoint inhibitors (ICI), both of which affect outcomes via modulating the immune system, is unclear. We investigated associations between self-reported, pretreatment physical activity and survival in a series of patients with cancer treated with ICI. METHODS:This retrospective cohort study included 930 patients treated with ICI who previously reported physical activity and had good performance status at treatment initiation. Hazards of death associated with increasing quartile of physical activity, measured as weekly metabolic equivalent of task minutes derived from the International Physical Activity Questionnaire (IPAQ), were estimated by multivariable Cox proportional hazards models adjusting for covariates. Alternative measures of physical activity based on IPAQ and consensus guidelines were also assessed. RESULTS:Increasing physical activity quartile was associated with a decreased adjusted hazard of death [adjusted HR (aHR) per one quartile increase, 0.89; 95% confidence interval (CI), 0.82-0.96]. Patients in the third and top quartile had a 24% (aHR = 0.76; 95% CI, 0.59-0.97) and 28% (aHR = 0.72; 95% CI, 0.55-0.93) reduced hazard of death compared with the bottom quartile, respectively. Results based on IPAQ and consensus guidelines and results from sensitivity analyses support findings from main analyses. CONCLUSIONS:Pretreatment physical activity is associated with increased survival among patients with cancer treated with ICI. Observational studies incorporating objective measurement and randomized interventional trials are needed to further establish the role of physical activity in improving ICI outcomes. IMPACT:Physical activity may be a promising interventional strategy to accompany ICI therapy to improve patient outcomes.

PURPOSE:Glioma arises from glial cells and comprises ∼80 % of malignant adult brain tumors. The polymorphic mitochondrial genome plays a key role in maintaining redox homeostasis and generation of reactive oxygen species (ROS). ROS have a well-established role in glial tumors. We investigated associations between germline mtDNA variants and haplogroups with glioma grade and glioblastoma (GBM) survival. METHODS:We conducted germline mtDNA sequencing for 388 patients (300 Caucasians, 88 African Americans [AA]) with incident glioma (105 non-GBM, 283 GBM). Across all patients we identified 1431 homoplasmic mtDNA variants, including 692 variants observed only in Caucasians, 474 only in AAs, and 265 in both groups. We estimated Odds Ratios (OR) and 95 % Confidence Intervals (CI) for mtDNA common variants, haplogroups, and gene variant burden in relation to glioma grade and tertiles of survival in GBM patients. Bonferroni and Benjamini-Hochberg correction were applied for multiple comparisons. RESULTS:No mtDNA haplogroup was associated with glioma grade or patient survival in GBM. Common variants m.3010G>A, m.195T>C, and m.16189T>C were linked to lower-grade glioma risk. For GBM survival, m.1719G>A, m.14766T>C, m.16129G>A, and m.204T>C were associated with a poorer prognosis while variant m.73A>G was associated with an improved prognosis. A higher variant burden in MT-ND1 and MT-ND5 was associated with a better prognosis. No results remained statistically significant after correction. CONCLUSION:This is the first comprehensive study of germline mtDNA sequence variation in relation to glioma grade at diagnosis and gliobastoma patient survival. Results warrant further study in larger populations and investigation of biologic mechanisms linking mtDNA polymorphism to these endpoints.

BACKGROUND:Patients with cancer report increasing rates of cannabis use, often to manage symptoms and toxicities. The efficacy and safety of cannabis, however, for some use cases remains unclear. To better understand characteristics of patients with cancer who report using cannabis, we examined data from a cannabis use survey of among patients with cancer seen at a National Cancer Institute-Designated Cancer Center. METHODS:In late 2021, patients with cancer (N = 1608) treated between July 2017 and December 2019 provided cannabis use data. Additional data were obtained from medical records data and routine patient-reported outcomes collected for clinical purposes. Univariable analyses and multivariable regression analyses were conducted to identify correlates of cannabis use at different stages in the cancer care trajectory. RESULTS:Rates of self-reported cannabis use by patients with cancer were 59% before cancer diagnosis and 47% after diagnosis. Longitudinal rates of cannabis use were 29% for no cannabis use, 23% before diagnosis, 12% after diagnosis, and 35% for both before and after diagnosis. Demographic factors associated with cannabis use included age, sex, race, and educational achievement. Tobacco use and binge drinking were associated with higher odds of cannabis use. Cannabis use was also associated with greater self-reported interference with physical functioning due to pain and interference with social functioning due to health problems. CONCLUSIONS:We found high rates of cannabis use among patients with cancer, both before and after their cancer diagnosis. Future studies should further investigate psychosocial factors associated with cannabis use among patients with cancer as well as psychosocial outcomes among patients with cancer using cannabis.

BACKGROUND:Although substance use may have adverse impacts on cancer outcomes, little is known regarding patterns of concurrent substance use with cannabis among cancer patients. Our objective was to examine predictors of concurrent substance use with cannabis among cancer patients since their cancer diagnosis and explore perceptions of cannabis among these patients. METHODS:Patients treated at a National Cancer Institute-designated comprehensive cancer center were invited to participate in an electronic survey regarding medical cannabis from August to November 2021. Survey data were linked to internal data resources including electronic health records and patient intake forms to obtain history of substance use (defined as within at least 3 months of cancer diagnosis) of cigarettes, injection drugs, high levels of alcohol, or clinically unsupervised prescription drugs (total n = 1094). Concurrent substance users were defined as those with any reported substance use and cannabis use at the time of cancer diagnosis. We used descriptive statistics (χ2 or exact tests) to compare groups and estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) to identify predictors of substance use among users and nonusers of cannabis. RESULTS:Approximately 45% (n = 489) of the sample reported cannabis use since their cancer diagnosis. Of patients who reported using cannabis, 20% self-reported concurrent polysubstance use, while 8% of cannabis nonusers reported substance use (P < .001). Among patients who use cannabis, those who reported 2 or more self-reported treatment-related symptoms (eg, pain, fatigue) were more likely to have self-reported concurrent substance use (AOR = 3.15, 95% CI = 1.07 to 9.27) compared with those without any symptoms. Among nonusers, those with lower educational background were more likely to have a history of concurrent substance use (AOR = 3.74, 95% CI = 1.57 to 8.92). Patients who use cannabis with concurrent substance use were more likely to report improved sleep (P = .04), increased appetite (P = .03), and treatment of additional medical conditions (P = .04) as perceived benefits of cannabis use. CONCLUSIONS:High symptom burden may be associated with concurrent substance use with cannabis among cancer patients.

BACKGROUND:The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis. METHODS:A total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples. RESULTS:Overall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use. CONCLUSION:This geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

BACKGROUND:There has been limited study regarding patient-provider communication about medical cannabis for cancer symptom management. To address this gap, this study assesses the determinants and prevalence of patient-provider communication about the use of medical cannabis for cancer symptoms at a National Cancer Institute-designated Comprehensive Cancer Center. METHODS:Individuals who completed cancer treatment from July 2017 to December 2019 were invited to participate in a survey regarding medical cannabis. An electronic survey was administered in English and Spanish from August to November 2021 and completed by 1592 individuals (response rate = 17.6%). RESULTS:About one-third (33.5%) of participants reported discussing medical cannabis for cancer symptom management with a health-care provider. Controlling for other factors, individuals with malnutrition and/or cachexia had higher odds (odds ratio [OR] = 2.30, 95% confidence interval [CI] = 1.50 to 3.53) of reporting patient-provider discussions compared with individuals without malnutrition and/or cachexia. Similarly, individuals with nausea had higher odds (OR = 1.94, 95% CI = 1.44 to 2.61) of reporting patient-provider discussions compared with individuals without nausea. A smaller percentage (15.6%) of participants reported receiving a recommendation for medical cannabis for cancer symptom management. Among individuals who reported using cannabis, a little over one-third (36.1%) reported not receiving instructions from anyone on how to use cannabis or determine how much to take. CONCLUSIONS:Overall, our study suggests that patient-provider communication about medical cannabis for cancer symptom management is limited. As interest and use of medical cannabis continues to grow among cancer patients, there is a need to ensure patients have access to high quality patient-provider communication.

PURPOSE We studied 571 patients with intracranial meningioma for clinical characteristics and tumor location associated with high grade meningioma (WHO II/III). MATERIALS AND METHODS Patients were participants in a multicentre epidemiologic study of risk factors for primary brain tumors including meningioma recruited from September 2005 to November 2019. We included patients 18 or older with a recent diagnosis of a primary intracranial meningioma of any subtype (ICD9/10: 9530-0, 9531-0, 9532-0, 9537-0, 9533-0, 9534-0, 9530-0, 9538-1, 9538-3) who were enrolled at neuro-oncology and neuro-surgery clinics in the southeastern U.S. RESULTS The median patient age was 58 years (IQR: 48-68) and the majority of patients were female (n = 415; 72.7%) and Caucasian (n = 516; 90.4%). Most patients were symptomatic (n = 460; 80.6%) and their tumours more commonly occurred in a non-skull base location (n = 298; 52.2%). A total of 86 patients (15.0%) had a WHO grade II/III meningioma. Compared to patients with WHO grade I tumours, patients with WHO II/III meningiomas were over 3-times more likely to be male (odds ratio (OR): 3.25; 95% confidence interval (CI): 1.98, 5.35) adjusting for age, race, symptomatic presentation, and skull-based location. Moreover, a WHO grade II/III meningioma was substantially less likely to be observed in asymptomatic patients (OR: 0.15, 95% CI: 0.04, 0.42), and in patients with a skull-based tumour (OR: 0.40, 95% CI: 0.24, 0.66), adjusting for other factors. Male gender, symptomatic tumour, and a non-skull base location were independently associated with WHO grade II/III meningioma. CONCLUSION These findings may shed additional light on the underlying pathogenesis of meningioma.

There has been limited study of patient-provider communication regarding medical cannabis for cancer symptoms. To address this gap, this study assesses the prevalence of patient-provider communication about the use of medical cannabis for cancer symptoms. Three types of communication are examined: 1) patient-provider discussions; 2) provider recommendations; and 3) provider instructions for how to use medical cannabis. We administered a survey from August to November 2021 with adult cancer patients who completed treatment from July 2017 to December 2019 at a National Cancer Institute designated Comprehensive Cancer Center; 1,592 individuals participated (response rate: 17.6%). About half of participants were female (52.1%). The age distribution of participants included 18-44 (9.4%), 45-54 (12.8%), 55-64 (25.3%), 65-74 (35.4%), and 75 and above (17.3%). Participant’s racial and ethnic background included Hispanic/Latinx (6.5%), African American/Black (4.0%), Asian American (1.0%), additional or multiple racial categories (3.5%), and White (91.5%). About a third (33.5%) of participants (530/1584) reported discussing medical cannabis for cancer symptoms with a healthcare provider. Participants who had discussed cannabis with a provider reported discussions with multiple providers including their oncology physician (62.3%), primary care provider (45.7%), oncology advanced practice provider (APP) (34.3%), dietician (7.4%), pharmacist (2.8%), and other healthcare provider (34.3%). Fewer (15.6%) participants (248/1592) reported receiving a recommendation for medical cannabis from a healthcare provider for their cancer symptoms. Participants who had received a recommendation reported recommendations from their oncology physician (32.7%), primary care provider (26.6%), oncology APP (13.7%), dietician (4.8%), pharmacist (1.6%), and other healthcare provider (56.9%). About a third (33.7%) of participants (537/1592) reported using medical cannabis during their cancer treatment and most often reported receiving instructions on how to use cannabis from no one (36.9%) or from a cannabis store or dispensary worker (23.8%). Less commonly, participants reported receiving instructions from their healthcare provider including their primary care provider (3.7%), oncology APP (2.0%), oncology physician (1.5%), pharmacist (<1%), or dietician (<1%). Based on this survey, about a third of cancer patients discuss medical cannabis with a healthcare provider but fewer receive a recommendation and/or instructions for how to use medical cannabis from a healthcare provider. Additional interventions may be needed to ensure that cancer patients interested in or currently using medical cannabis receive guidance from oncology care providers. Citation Format: Kea Turner, Jessica Y. Islam, Yessica C. Martinez, Omar Garcia Rodriguez, Diane Rodriguez Irlanda, Oliver T. Nguyen, Heather S.L. Jim, Kathleen M. Egan. Patient provider communication about the use of medical cannabis for cancer symptoms. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4374.

The broad and long-term goal of this study is to support the biobanking of fecal samples for development of prospective microbiome cohorts in large and diverse study populations. The gut microbiome, comprising trillions of microbes residing in the gut, is involved in the etiology of multiple health conditions, with emerging evidence for a role in cancer. Establishing a role for the microbiome in cancer risk has been difficult since, at present, availability of pre-diagnostic fecal specimens is severely limited in existing cohorts to study prospective microbiome-cancer associations. To advance knowledge in the field, it is critical to establish prospective microbiome cohorts that include samples from diverse study populations. Mounting evidence supports that the collective activity of the gut microbiota may influence development and progression of colorectal cancer (CRC), the second overall leading cause of cancer death in the United States. There are persistent CRC disparities in the US-with African Americans and those living in rural areas suffering higher CRC incidence and mortality. Explanations for CRC disparities are likely multifactorial, involving differences in lifestyle, socioeconomic, social, and other environmental exposures. These exposures likely act individually and interact to affect gut microbiome composition, resulting in the variation of microbiome-CRC associations across race/ethnicity and geographic location. Yet, microbiome-mediated mechanisms for CRC disparities remain largely unstudied. To advance knowledge in the field, future microbiome studies should encompass diverse study populations, include those with limited access to direct-to-colonoscopy screening, and collect detailed data on targetable exposures that alter the microbiome and drive CRC disparities. Moffitt Cancer Center is presently implementing multilevel, evidence-based CRC screening intervention programs aiming to expand access to CRC screening and improve screening rates in the community setting. These programs leverage fecal immunochemical tests (FIT), which are cost-effective and preferable for CRC screening in diverse patient populations without access to colonoscopy. Our preliminary data indicate that the fecal microbiome can be characterized in residual FIT samples using both 16S rRNA and metagenomic sequencing. The FIT microbial profiles were stable after multiple days at room temperature and were comparable to the field ‘gold-standard’. Therefore, CRC screening programs to improve FIT screening uptake provide ideal infrastructure to prospectively collect fecal specimens in diverse, unreached populations. Extending our findings of the suitability of FIT for microbiome assessment is a critical first step to move the field forward and to establish infrastructure for future population-based research on the microbiome and cancer disparities. As a speaker in a major session at AACR, I will describe our efforts to support large, multicenter grants that focus on establishing prospective microbiome and cancer cohorts. I will update the audience on our progress in completing the following specific aims: Specific Aim 1: Implementing baseline and repeat collection and storage of residual FIT samples in community clinics in the Tampa Bay Area leveraging existing FIT screening infrastructure. Subjects complete FIT testing following standard protocols, and, after hemoglobin testing, the residual sample is processed and stored in -80°C freezers at Moffitt Cancer Center. Participants complete baseline questionnaires and data are linked to medical record and Florida cancer registry data for active prospective follow-up. We began our pilot study in a small, low-traffic clinic to establish our study workflow. We have recently expanded the study, recruiting N=37 participants. With continued expansion to larger clinics in the Tampa Bay Area, we estimate we will have recruited > 100 participants by March 2023. Specific Aim 2: To inform larger-scale studies,we will validate the use of FIT samples for investigating associations of the microbiome with colorectal neoplasms. To do this, we will pilot a shotgun metagenomic sequencing approach to characterize the fecal microbiome in residual FIT samples from Aim 1. We will sequence the metagenome among 1) those who tested positive on the FIT and subsequently were diagnosed with advanced adenoma, an established precursor to CRC, via colonoscopy (N=20); 2) those who tested negative on the FIT at baseline (N=20); and 3) those who tested negative on the FIT at baseline with a second negative FIT collected 2-years after baseline (N=20 repeat samples). Then, we will quantify the percentage of FIT samples successfully metagenomically sequenced, compare our microbiome-adenoma findings to previous fecal microbiome studies, and estimate stability of the FIT microbiome over 2 years. Impact and future directions: We will demonstrate support for expanding collection and use of residual FIT samples as a practical, cost-effective approach for investigating associations of the microbiome with disease in diverse study populations. In the future, our biobank will serve as a distinctive resource to study prospective microbiome-disease associations. Future directions include additional pilot studies supporting the use FIT samples for microbiome research, establishing multicenter collaborations, and larger-scale investigations of prospective associations of the FIT microbiome with CRC. Citation Format: Doratha A. Byrd. A biobank of Fecal Immunochemical Tests (FIT) for gut microbiome measurement: A paradigm for studying the microbiome and cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr NG09.

The gut microbiome is a potentially important contributor to endogenous estrogen levels after menopause. In healthy postmenopausal women, we examined associations of fecal microbiome composition with levels of urinary estrogens, their metabolites, and relevant metabolic pathway ratios implicated in breast cancer risk. Eligible postmenopausal women (n = 164) had a body mass index (BMI) ≤ 35 kg/m2 and no history of hormone use (previous 6 months) or cancer/metabolic disorders. Estrogens were quantified in spot urine samples with liquid chromatography-high resolution mass spectrometry (corrected for creatinine). Bacterial DNA was isolated from fecal samples and the V1–V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of gut microbiome’s indices of within-sample (alpha) diversity (i.e., Shannon, Chao1, and Inverse Simpson), phylogenetic diversity, and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with individual estrogens and metabolic ratios, adjusted for age and BMI. In this sample of 164 healthy postmenopausal women, the mean age was 62.9 years (range 47.0–86.0). We found significant inverse associations of observed species with 4-pathway:total estrogens (p = 0.04) and 4-pathway:2-pathway (p = 0.01). Shannon index was positively associated with 2-catechols: methylated 2-catechols (p = 0.04). Chao1 was inversely associated with E1:total estrogens (p = 0.04), and 4-pathway:2-pathway (p = 0.02) and positively associated with 2-pathway:parent estrogens (p = 0.01). Phylogenetic diversity was inversely associated with 4-pathway:total estrogens (p = 0.02), 4-pathway:parent estrogens (p = 0.03), 4-pathway:2-pathway (p = 0.01), and 4-pathway:16-pathway (p = 0.03) and positively associated with 2-pathway:parent estrogens (p = 0.01). F/B ratio was not associated with any of the estrogen measures. Microbial diversity was associated with several estrogen metabolism ratios implicated in breast cancer risk. Further studies are warranted to confirm these findings in a larger and more representative sample of postmenopausal women, particularly with enrichment of minority participants.

Supplementary Table 2 from A Multistage Association Study Identifies a Breast Cancer Genetic Locus at <i>NCOA7</i>

Supplementary Table 1 from A Multistage Association Study Identifies a Breast Cancer Genetic Locus at <i>NCOA7</i>

Supplementary Figure 1 from A Multistage Association Study Identifies a Breast Cancer Genetic Locus at NCOA7

Abstract Combination immune checkpoint inhibitors (ICI) can affect durable response in melanoma brain metastases (MBM) but have largely been ineffective for the treatment of glioblastoma (GBM), a primary brain tumor. Recent studies in animal models and humans have suggested that the microbe composition of the gut can influence the effectiveness of ICI in melanoma and other cancers. Our central hypothesis is that the gut microbiome can influence immunotherapy responsiveness for GBM patients. We obtained microbiome (stool) samples from GBM and MBM patients prior to beginning any treatment or surgical interventions. We then transplanted these microbiome samples into gnotobiotic mice to create humanized microbiome mice. We transplanted two GBM patients and two MBM patients microbiome samples to create 4 unique patient-derived humanized microbiome mouse lines (GBM1, GBM2, MBM1, and MBM2). Using 16s ribosomal RNA microbiome sequencing, we found that each patient-derived microbiome mouse line had a unique microbiome composition as measured by relative abundance and diversity of species. Mice from each line were then intracranially injected with GL261 murine glioma cells and treated with the ICI anti-PD-1 or isotype control. We found that MBM1 and GBM2 mice were resistant to anti-PD-1 and did not display prolonged survival with anti-PD-1 treatment. However, GBM1 and MBM2 mice were positive responders to anti-PD-1 and displayed significantly prolonged survival compared to isotype control. Additional microbiome sequencing analyses are ongoing that will reveal positive microbiome profiles among these patient-derived lines, and additional GBM and MBM patient-derived microbiome lines are being created and tested for immunotherapy efficacy. Ultimately, understanding how certain microbial communities can enhance the effectiveness of immunotherapy may lead to the development of new approaches that include modification or transplantation of microbe communities in GBM patients for increased therapeutic impact.

Abstract Introduction: Colorectal cancer (CRC) poses a disproportionate burden among certain Hispanic/Latino subgroups, such as Puerto Rican and Cuban individuals, and Black individuals. Causes of CRC disparities are poorly understood but are likely driven by social determinants of health (SDOH), which may directly and indirectly influence the gut microbiome (GM). In turn, the GM is increasingly implicated in colorectal carcinogenesis. Therefore, it is plausible that the GM may be targeted to reduce excess CRC burden among disproportionately affected populations. However, prior studies of the GM and CRC had limited inclusion of underserved populations and limited collection of SDOH data. Objective: To clearly define the role of the GM in CRC and other cancer disparities, we conducted a pilot study to establish a well-annotated cohort that includes longitudinally collected fecal specimens among diverse populations. Methods: We leveraged fecal immunochemical tests (FIT), a cost-effective method for CRC screening in patient populations with limited access to colonoscopy, in which the GM can be well characterized. Participants completed annual FIT testing following standard protocols as implemented in a Federally Qualified Health Center. FIT samples were processed and banked at Moffitt Cancer Center in -80ºC freezers. All participants completed stool and risk factor questionnaires capturing SDOH, medical history, diet, and lifestyle exposures. To further validate the FIT microbiome, we extracted DNA from 8 sets of triplicate FIT aliquots (200ul each) using the automated MagCore®️ DNA Kit and then performed shotgun sequencing to characterize the fecal microbiome. To test for quality of the data and to compare microbiome metrics (e.g., alpha diversity and microbial abundances) in replicate samples, we calculated intraclass correlation coefficients (ICCs) using linear mixed effects models. Results: In just one clinic, to date, more than N=79 individuals who are primarily Spanish speakers and persons from other racial/ethnic minority subgroups have been enrolled. The racial and ethnic distribution included 39% Mexican, 11% Black, 6% Puerto Rican, 9% Central or South American, and 5% Cuban individuals. Approximately, 59% of the consented population preferentially spoke Spanish and 14% tested positive on the FIT. In the pilot FIT testing samples, we found that the integrity of the DNA was high, with only a few (N=3 of 24) samples with insufficient DNA yield for shotgun metagenomic sequencing. ICCs were generally above ≥ 95% for alpha diversity metrics and abundance of species/genes indicating excellent handling and processing procedures for FIT microbiome extraction and sequencing. Conclusion: Our findings support the concept that FIT-based community screening programs offer exceptional opportunity for GM research in diverse, underrepresented populations. Our future studies will integrate the SDOH data and expand this cohort with the goal of contributing novel insights regarding associations of the GM with early pathogenesis of CRC across diverse populations. Citation Format: Doratha Byrd, Stephanie Hogue, Xuefeng Wang, Sugriva Forsyth, Martha Fuentes, Kathleen Egan, Tiffany Carson, Youngchul Kim, Jessica Islam, Cathy Meade, Clement Gwede. A biobank of fecal immunochemical tests (FIT) to study gut microbiome-mediated cancer disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B074.

PDF file, 36K, Number of risk allele carriers.

Intratumoral heterogeneity is a defining hallmark of glioblastoma, driving drug resistance and ultimately recurrence. Many somatic drivers of microenvironmental change have been shown to affect this heterogeneity and, ultimately, the treatment response. However, little is known about how germline mutations affect the tumoral microenvironment. Here, we find that the single-nucleotide polymorphism (SNP) rs755622 in the promoter of the cytokine macrophage migration inhibitory factor (MIF) is associated with increased leukocyte infiltration in glioblastoma. Furthermore, we identified an association between rs755622 and lactotransferrin expression, which could also be used as a biomarker for immune-infiltrated tumors. These findings demonstrate that a germline SNP in the promoter region of MIF may affect the immune microenvironment and further reveal a link between lactotransferrin and immune activation.

Supplementary Table 1 from A Multistage Association Study Identifies a Breast Cancer Genetic Locus at NCOA7

The recent National Institute of Health (NIH) INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative has bolstered capacity for the current increase in clinical trials involving individuals with Down syndrome (DS). This new NIH funding mechanism offers new opportunities to expand and develop novel approaches in engaging and effectively enrolling a broader representation of clinical trials participants addressing current medical issues faced by individuals with DS. To address this opportunity, the NIH assembled leading clinicians, scientists, and representatives of advocacy groups to review existing methods and to identify those areas where new approaches are needed to engage and prepare DS populations for participation in clinical trial research. This paper summarizes the results of the Clinical Trial Readiness Working Group that was part of the INCLUDE Project Workshop: Planning a Virtual Down Syndrome Cohort Across the Lifespan Workshop held virtually September 23 and 24, 2019.

Glioma is an aggressive neoplasm of the brain with poorly understood etiology. A limited number of pathogens have been examined as glioma risk factors, but data from prospective studies with infection status determined before disease are lacking. Herpesviruses comprise a large family of DNA viruses that infect humans and are linked to a range of chronic diseases. We conducted a prospective evaluation of the association between antibody to six human herpesviruses and glioma risk in the Janus Serum Bank (Janus) and the Cancer Prevention Study‐II (CPS‐II). In Janus and CPS‐II, the risk for glioma was not related to seroprevalence of herpes simplex virus‐1, varicella zoster virus, or human herpes viruses 6A or 6B. In Janus, seropositivity to either the Epstein Barr virus (EBV) EA[D] or VCAp18 antigen was associated with a lower risk of glioma (ORs: 0.55 [95% CI 0.32‐0.94] and 0.57 [95% CI 0.38‐0.85]). This inverse association was consistent by histologic subtype and was observed for gliomas diagnosed up to two decades following antibody measurement. In Janus, seropositivity to at least one of three examined cytomegalovirus (CMV) antigens (pp150, pp52, pp28) was associated with an increased risk of nonglioblastoma (OR: 2.08 [95% CI 1.07‐4.03]). This association was limited to tumors diagnosed within 12 years of antibody measurement. In summary, we report evidence of an inverse association between exposure to EBV and glioma. We further report that CMV exposure may be related to a higher likelihood of the nonglioblastoma subtype.