Importance:BRCA genetic testing is critical for cancer risk assessment, treatment and personalization, yet substantial underutilization persists. Socioeconomic and clinical factors may strongly influence testing uptake; therefore, identifying the potential drivers to BRCA testing and treatment is essential for addressing gaps in access, increasing retention into care, and improving cancer outcomes. Objective:To quantify the putatively causal effects of SDoH on BRCA genetic testing among individuals with breast, ovarian, pancreatic, and prostate cancers and to develop a predictive model to identify patients at risk for underuse of testing. Design Setting and Participants:This observational case-control study used data from a large multistate clinical research data network covering southern US (2012-2023). The network contained records of more than 26 million individuals and was linked with ZIP code-level SDoH variables derived from national socioeconomic datasets. Adults diagnosed with breast, ovarian, pancreatic, or prostate cancer were eligible for cases (received BRCA testing) or controls (did not receive BRCA testing, matched by cancer diagnosis). Exposure:SDoH categories, including economic conditions, education, healthcare access, neighborhood conditions, and social connectedness. Main Outcomes and Measures:The primary outcome was receipt of BRCA genetic testing after cancer diagnosis. Results:Among 3,279 people diagnosed with cancer, 748 received BRCA testing and 2,531 served as controls. Study population's mean [SD] age was 66.8 [15.7] years; 1,758 were women [53.6%], 2,238 [69.6%] were White and 616 [18.8%] were Black or African American. Breast (1,420 [42.8%]) and prostate (1,342 [40.9%]) cancers were the most common diagnoses, followed by pancreatic (242 [7.4%]), ovarian (238 [7.2%]), and multiple cancers (55 [1.7%]). Upon adjusting for potential confounding, higher educational attainment (odds ratio [OR], 1.19), public-sector employment (OR, 1.42), neighborhood safety (OR, 1.28), and social participation (OR, 1.72) showed an increased likelihood of undergoing BRCA testing, whereas economic instability, including housing cost burden and reliance on public insurance, had an effect of reduced testing. A random forest classifier demonstrated good discriminative performance (AUROC, 0.776) to predict cancer patients who were likely to take BRCA testing, where nativity, language, and residential stability ranked among the most influential social determinants according to SHapley Additive exPlanations (SHAP) analysis. Conclusions and Relevance:In this observational case-control study, SDoHs were strongly associated with receipt of BRCA genetic testing among people with cancer. These findings suggest that disparities in genetic testing may reflect structural and social barriers rather than differences in clinical eligibility alone. Efforts to improve equitable access to genetic testing may benefit from integrating social-context information into clinical workflows and targeting outreach or navigation strategies toward socially disadvantaged populations. Key Points:Question: Do socioeconomic and clinical circumstances contribute to care access gaps to BRCA genetic testing among people with breast, ovarian, prostate, and pancreatic cancers? Findings: In a case-control study of 3,279 adults with cancer from a large multi-state US clinical research data network, multiple social determinants of health, including economic conditions, education, healthcare access, neighborhood conditions, and social connectedness, were identified as key determinants of BRCA genetic testing uptake, with variation across age and sex groups. Meaning: Improving equal access to BRCA genetic testing may require interventions that address financial barriers and strengthen social, and community supports that influence engagement with genetic services.

Abstract Introduction: Knowledge and awareness of colorectal cancer (CRC) prevention and genetic testing remain limited in many Los Angeles County (LAC) communities. To address this, we trained 42 CRC-specialized community health workers (CoGENES) through a train-the-trainer program. We present preliminary results of a community-based randomized controlled trial (RCT) to evaluate the impact of materials and training delivered by CoGENES as part of an NCI funded PE-CGS network program at USC. Methods: A two-armed, single blinded RCT was launched in August 2024. Participants are ≥ 18 years of age and residents of LAC. The intervention included the delivery of an educational session by CoGENES and an a priori developed educational handbook. The control group received standard CRC and genetic testing materials. Data on demographics, acculturation, cultural values and fatalism, health literacy, numeracy, generalized self-efficacy (GSE), genomic knowledge, cancer prevention behaviors and attitudes, were collected at baseline with validated or team-developed surveys. Follow-up surveys at 6-12 weeks and 6-8 months after intervention receipt evaluate changes in GSE, genomic knowledge, and cancer prevention behaviors. Paired dietary changes were evaluated using McNemar’s test. Paired t-tests and independent t-tests were used to compare baseline and follow-up results within and between arms, respectively. Results: A total of 138 participants (mean age = 48.8 years, SD = 13.6) were randomized to the intervention (n = 72) or control (n = 66) arm, with no baseline differences. All were Hispanic/Latine, most were female (83%), Mexican (64%), Catholic (61%), married (50%), completed ≤11th grade education (51%), and spoke primarily Spanish (69%). Interim analyses showed that by 6-8 weeks, participants in the intervention arm demonstrated improved dietary behaviors, with a higher proportion limiting processed food intake (rarely or never: 48.6% at baseline vs 69.8% at follow-up; p <0.05). We observed significant improvements in cancer genetic knowledge within the intervention arm at 6-12 weeks, with more correct answers (mean difference = 4.32; p <0.01), and fewer “don’t know” responses (mean difference = -5.40; p<0.01). These improvements were greater than in the control arm: 2.7 more correct answers (p<0.01) and 3.25 fewer “don’t know” responses (p<0.01). Genetic literacy and comprehension scores also improved (mean difference = 11.38; p < 0.01), though not significantly more than in the control group (difference-in-differences = 2.20; p = 0.43). Conclusion: We present preliminary evidence that deploying CRC prevention trained educators in a community setting, may improve CRC genetic knowledge, and highlights opportunities and willingness to improve lifestyle and dietary patterns to reduce CRC incidence. Citation Format: Bianca Rosales, Diego Alvarez-Lopez, Janet Rodriguez, Joel Sanchez Mendez, Charité N. Ricker, Rosa Barahona, Heinz Josef Lenz, Lourdes Baezconde-Garbanati, Mariana C. Stern. Preliminary results of a community-based randomized controlled trial to raise colorectal cancer awareness: The Community Genetic Navigation Engagement Specialist (CoGENES) Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 923.

Colorectal cancer (CRC) has increased at an alarming rate amongst younger (< 50 years) individuals. Such early-onset colorectal cancer (EOCRC) has been particularly notable within the Hispanic/Latino population. Yet, this population has not been sufficiently profiled in terms of two critical elements of CRC -- the MYC proto-oncogene and WNT signaling pathway. Here, we performed a comprehensive multi-omics analysis on 30 early-onset and 37 late-onset CRC (≥ 50 years) samples from Hispanic/Latino patients. Our analysis included DNA exome sequencing for somatic mutations, somatic copy number alterations, and global and local genetic similarity. Using RNA sequencing, we also assessed differential gene expression, cellular pathways, and gene fusions. We then compared our findings from early-onset Hispanic/Latino patient samples with publicly available data from Non-Hispanic White cohorts. Across all early-onset patients, which had a median 1000 Genomes Project Peruvian-in-Lima-like (1KG-PEL-like) genetic similarity proportion of 60%, we identified 41 WNT pathway genes with significant mutations. Six important examples were APC, TCF7L2, DKK1, DKK2, FZD10, and LRP5. Notably, patients with mutations in DKK1 and DKK2 had the highest 1KG-PEL-like proportion (79%). When we compared the Hispanic/Latino cohort to the Non-Hispanic White cohorts, four of these key genes -- DKK1, DKK2, FZD10, and LRP5 -- were significant in both risk association analyses and differential gene expression. Interestingly, early-onset tumors (vs. late-onset) exhibited distinct somatic copy number alterations and gene expression profiles; the differences included MYC and drug-targetable WNT pathway genes. We also identified a novel WNT gene fusion, RSPO3, in early-onset tumors; it was associated with enhanced WNT signaling. This integrative analysis underscores the distinct molecular features of EOCRC cancer in the Hispanic/Latino population; reveals potential avenues for tailored precision medicine therapies; and emphasizes the importance of multi-omics approaches in studying colorectal carcinogenesis. We expect this data to help contribute towards reducing cancer health disparities. Significance:This study offers multi-omics profiling analysis of early-onset colorectal cancer (EOCRC) in an underserved community, explores the implications of MYC gene and WNT pathway alterations, and provides critical insights into cancer health disparities.

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.

Knowledge, attitudes, and beliefs (KAB) about genetics impacts engagement in genetics and genomics research, but there is a lack of data about these constructs among Hispanic/Latinos (H/L). Adult H/L patients with colorectal cancer were recruited at a public (Los Angeles General) and a private (USC Norris Cancer Hospital) hospital to complete a cross-sectional survey assessing KAB. Recruitment and survey administration was done in Spanish or English. Preliminary analysis of 56 surveys found that most participants were from the public hospital (93%), born outside the US (84%), Spanish speaking (71%), and male (63%); median age was 55 years and acculturation was low [1.89 (SD 1.25); scale 1-5]. Low to mid-range scores were found for genetic literacy [3.45 (SD 1.49); scale 1-7], genetic knowledge [9.63 (SD 6.03); scale 0-25], cancer knowledge [2.20 (SD 1.24); scale 0-5]; and tumor genomics knowledge [3.62 (SD 0.78); scale 0-6]. Although 51% agreed they would want to be contacted for future research, 33% expressed uncertainty. When asked about genetic research, > 90% agreed it is medical progress. Almost 90% would want to know if their disease was hereditary, >80% would inform relatives about genetic results, and 29% agreed they were concerned about genetic testing impacting their ability to stay in this country. Participants had limited genetic literacy, genetic, cancer and tumor genomics knowledge. Most expressed interest and positive feelings towards genetic testing and genomic research; however, there were uncertainties and concerns to consider in future research to improve H/L engagement in genetics research. Charite Ricker, Daisy Hernandez, Itzya Ulloa, Elena Taylor, Blanca Ovalle, Bo Yuan, Juan Pablo Lewinger, Rosa Barahona, Caryn Lerman, Julie O. Culver, Mariana Stern, John Carpten, Heinz-Josef Lenz, Lourdes A. Baezconde-Garbanati. Genetic and genomic knowledge, attitudes, and beliefs among Hispanic/Latinos with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7487.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths globally. While CRC rates have stabilized or decreased in affluent nations, cases among younger individuals are rising, particularly in Hispanic/Latino (H/L) populations, who show the highest increase in early-onset (<50) CRC (EOCRC) in the U.S. Despite this, H/L populations remain underrepresented in molecular profiling studies. Key aspects of CRC molecular characterization, critical to tumorigenesis, include the MYC proto-oncogene and the WNT signaling pathway. We performed a multi-omics analysis of 67 CRC Tumor/Normal samples —30 early-onset (EO) and 37 late-onset (LO)— from Hispanic/Latino (H/L) patients as part of the Cancer Moonshot Initiative's Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Molecular characterization involved whole-exome sequencing to identify somatic mutations, somatic copy number alterations (SCNAs), and both global and local genetic similarities (a term recommended by NASEM for genetic ancestry). RNA sequencing was used to assess differential gene expression, cellular pathways, and gene fusions. Finally, EO H/L samples were compared to public data such as AACR Project GENIE dataset, specifically from 3,578 Non-Hispanic White (NHW) cohorts, to provide broader context. As well, we incorporated three CRC samples with spatial transcriptomic (ST) data from the 10x Genomics database, analyzed using bioinformatics tools and integrated with clinical and genomic data —translational research. Following NASEM guidelines, we adhered to best practices for population descriptors in genetics and genomic research. EO samples, with a median 60% genetic similarity to the 1000 Genomes Project Peruvian-in-Lima (1KG-PEL) population, showed significant mutations in 41 WNT pathway genes, including APC, TCF7L2, DKK1, DKK2, FZD10, and LRP5. Samples with DKK1 and DKK2 mutations had the highest 1KG-PEL-like proportion (79%). Four key genes—DKK1, DKK2, FZD10, and LRP5—were significant in both risk association and differential expression analyses between H/L and NHW cohorts. EO tumors displayed unique SCNAs and gene expression profiles, notably in MYC and drug-targetable WNT pathway genes, compared to LO tumors. Also, a novel WNT gene fusion, RSPO3, linked to increased WNT signaling, was identified in EO tumors. Lastly, ST analysis uncovered distinct functional patterns of WNT-related genes across tumor components, including cancerous, immune, and stromal regions. This study characterizes EOCRC in the H/L population, uncovering unique genomic and transcriptomic features that inform precision oncology and highlight the importance of addressing cancer health disparities through multi-omics analysis. Francisco Gutierrez Carranza, Brigette Waldrup, Yuxin Jin, Yonatan Amzaleg, Mackenzie Postel, David W. Craig, John D. Carpten, Salhia Badour, Daisy Hernandez, Natalia Gutierrez, Charite N. Ricker, Julie O. Culver, Carmen E. Chavez, Mariana C. Stern, Lourdes Baezconde-Garbanati, Heinz-Josef Lenz, Enrique I. Velazquez-Villarreal. Multi-omics analysis of MYC gene and WNT signaling pathway alterations in early-onset colorectal cancer in Hispanic/Latino patients, enhanced with spatial transcriptomics approaches [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3742.

Polygenic risk scores (PRS), a measure that sums multiple common genetic susceptibility variants into a single burden measure, can help identify individuals at higher risk for colorectal cancer (CRC). Consequently, there is growing interest in its potential use to guide screening practices, despite the current lack of evidence-based guidelines on the clinical utility of PRS models. Therefore, there is a need to understand the potential challenges and factors associated with PRS use in primary care settings. This qualitative study explores the perceptions of healthcare providers with PRS information to guide CRC screening decisions in the primary care setting. Using an exploratory approach, we conducted semi-structured interviews with 10 healthcare providers. The socioecological model guided the development of the interview questions. Transcripts were coded based on emergent themes. A total of seven themes were identified in this study, and each was organized using the socioecological model at the individual, interpersonal, community, and organizational levels. One key finding was the limited knowledge of PRS and the distinction between PRS and genetic testing for high-penetrant germline mutations. Providers shared the need for training, education, and comprehensive clinical guidelines for the use of PRS. This study provides insights to better optimize genetic education, testing, access, and care for improved CRC screening in at-risk individuals.

ImportanceEnhanced breast cancer screening with magnetic resonance imaging (MRI) is recommended to women with elevated risk of breast cancer, yet uptake of screening remains unclear after genetic testing.ObjectiveTo evaluate uptake of MRI after genetic results disclosure and counseling.Design, Setting, and ParticipantsThis multicenter cohort study was conducted at the University of Southern California Norris Cancer Hospital, the Los Angeles General Medical Center, and the Stanford University Cancer Institute. Patients were recruited from July 1, 2014, through November 30, 2016. Following multiplex gene panel testing and genetic counseling, patients responded to surveys about breast MRI screening at 3, 6, 12, and 24 months and to a final survey between 3 and 4 years after counseling. Participants met standard clinical criteria for genetic testing or had a 2.5% or greater probability of inherited cancer susceptibility. Patients were categorized based on breast cancer risk from genetic testing results and Tyrer-Cuzick model-calculated risk as having (1) a BRCA or other high-risk pathogenic variant (PV), (2) a moderate-risk PV, (3) a higher lifetime breast cancer risk (≥20%), or (4) a lower lifetime breast cancer risk (<20%). Analysis was conducted from September 28 to November 9, 2023.InterventionsGenetic testing with a 25- or 28-gene panel, and pretest and posttest genetic counseling by a genetic counselor or an advanced practice genetics nurse practitioner, which included cancer-specific screening recommendations.Main Outcomes and MeasuresMRI screening adherence over time across risk groups was estimated using Cox proportional hazards regression modeling. Likelihood of screening adherence (odds ratios [ORs] with 95% CIs), controlling for potential confounders, was estimated using logistic regression.ResultsThis study included 638 patients, with a mean (SD) age of 50.7 (13.3) years at testing. There were 43 patients (6.7%) with a BRCA or other high-risk PV, 16 (2.5%) with a moderate-risk PV, 146 (22.9%) with higher lifetime breast cancer risk, and 433 (67.9%) with lower lifetime breast cancer risk. A total of 52 patients (8.2%) identified as Asian, 21 (3.3%) as Black, 271 (42.5%) as Hispanic, and 255 (40.0) as White. Compared with patients with lower lifetime breast cancer risk, patients with a BRCA or other high-risk PV and those with a moderate-risk PV were approximately 10 times (OR, 9.81 [95% CI, 4.05-23.86]; P < .001) and 4 times (OR, 4.12 [95% CI, 1.10-14.35]; P = .03) as likely to undergo MRI, respectively. Patients with a BRCA or other high-risk PV were nearly 16 times (OR, 15.81 [95% CI, 5.17-48.31]) as likely to report consistent yearly MRI screening compared with patients with lower lifetime risk.Conclusions and RelevanceIn this study, women with inherited PVs conferring increased breast cancer risk had higher and more consistent MRI uptake than women with lower estimated risk. These findings emphasize the importance of genetic cancer risk assessment for effective enhanced breast cancer screening.

Hispanic/Latino (H/L) populations are disproportionally affected by colorectal cancer (CRC). This disparity is driven by a lack of awareness about CRC prevention, genetic testing, and access to culturally appropriate resources. A CoGENES train-the-trainer program was develop for a workforce of community health workers (CHWs) as part of COPECC, a Cancer Moonshot NCI funded PE-CGS network program at USC. After development and testing with community input, the program was implemented in three phases. Phase 1: Twelve CHWs participated in six in-person sessions over three weeks in Spanish/English, which provided knowledge on CRC/genetic testing, and community education strategies. Phase 2: the trained CoGENES replicated the sessions within their respective H/L communities training 30 more CoGENES. Phase 3: all 42 CoGENES are disseminating information through community events using the CoGENES training manual, to sustain long-term community impact. Data was collected on the number of individuals educated, events attended, and CRC/genetic testing information disseminated. Demographic and acculturation information was collected through surveys. Self-confidence to train others was measured at baseline, after training completion, at a 6 and 12 month follow-up, using a team-developed nine-item tool. All p-values are two-sided from paired t-tests. Majority of the participants were female (phase 1 = 75%, phase 2 = 79%) Mexico-born (92% & 75%), and very Latino oriented (67% & 71%). We saw a statistically significant increase in the “self-confidence to train others” in 8/9 items and 7/9 items of the survey for Phase 1 and Phase 2 CoGENES after they received the training (p-values <0.05). The level of self-confidence was sustained at 6 and 12 months, with no difference in the mean values of the items when compared to post-training values in Phase 1 CoGENES (p-values >0.05). In Phase 2 CoGENEs, we saw a decrease in the mean values for 5/9 items in the survey for the 12-month follow-up when compared to after training (p-values <0.05). Despite this, all the values remained higher at 12-months than at baseline. The difference between baseline and 12-month follow-up was the confidence to “describe what genetic tumor testing is” (p = 0.016) in Phase 1 CoGENES, and the confidence to “describe what genetic counseling is” (p = 0.017) in Phase 2 CoGENES. The CoGENES train-the-trainer program, a culturally tailored linguistically specific approach to address disparities in CRC prevention and genetic testing within H/L communities. Results show a lasting increase in the self-confidence of participants to empower other individuals in their communities to disseminate CRC prevention knowledge. The CoGENES CHWs partnered with 20 community-based organizations, reaching over 3 million people through community events, media interviews, podcasts, and workshops. Bianca Rosales, Janet Rodriguez, Joel Sanchez Mendez, Yaneth L. Rodriguez, Charite Ricker, Rosa Barahona, Heinz Joseph Lenz, John Carpten, Mariana C. Stern, Lourdes A. Baezconde-Garbanati. Self-confidence as a driver of community impact: Outcomes of the Community Genetic Navigation Engagement Specialist (CoGENES) train-the-trainer program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4027.

Breast cancer (BC) is one of the most common cancers globally. Genetic testing facilitates screening and informs targeted risk-reduction and treatments. However, genes included in testing panels are from European-ancestry studies. We conducted a pooled case-control analysis in self-identified Hispanic/Latina women (4178 cases and 4344 controls), using whole exome sequencing and a targeted panel. We tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. Using logistic regression, we found a strong association of LoF variants in FANCM with ER-negative BC (p = 4.1 × 10-7), odds ratio [confidence interval]: 6.7 [2.9-15.6]). Among known susceptibility genes, BRCA1, BRCA2, and PALB2 strongly associated with BC. FANCM was previously proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested clinically. Our results demonstrate that FANCM should be added to BC gene panels.

Patients in the United States with Limited English Proficiency (LEP) lack access to language‐concordant genetic counselors. This places patients with LEP at a disadvantage during appointments due to previously identified factors such as time constraints, lack of formal training for genetic counselors, and interpreters' limited training in genetics terminology. When done well, interpretation services enhance healthcare and expand access to genetic counseling. Given the increased utilization of telehealth for the delivery of genetic counseling services including telephone and video communication, it is imperative to adapt practices to avoid exacerbating disparities among underserved communities. This qualitative study explores strategies used by experienced genetic counselors (GCs) in telehealth sessions with interpreters. Participants were board‐certified GCs and had high‐volume of patients with LEP seen via telehealth. Semi‐structured interviews ( n = 11) were conducted virtually and recorded. Interviews were coded for themes using descriptive coding. Development of the codebook was done with study team members reviewing 1–2 transcripts against the initial codebook for feedback. Codes and the codebook were refined through an iterative process. Thematic analysis revealed two major themes: how GCs gained their knowledge, and strategies GCs used during interpreted telehealth appointments. Experienced GCs gained their knowledge through on‐the‐job experience, learning from interpreters, and from bilingual colleagues. Results also indicated that when providing services over telehealth for patients with LEP, experienced GCs employ strategies to overcome difficulties in educating, assessing patient understanding, and meeting psychosocial needs. These strategies build on GC core competencies and best practices for working with interpreters to adapt for telehealth delivery. As such, this study offers practical guidance for GCs and trainees with suggestions before, during, and after an interpreted telehealth appointment. GCs can make strides for equity in the quality of telehealth sessions for patients regardless of language by leveraging these insights, learning about the cultures of the communities they frequently serve, and willingness to adapt sessions.

We explored the impact of language discordance (LD) on quality of care by asking genetic counselors (GCs) about their perception of how their lack of proficiency in a patient's language affects their sessions. We hypothesized that contracting, which relies on ongoing, bidirectional communication between GC and patient, is particularly vulnerable to LD. Specifically, we evaluated the impact of dialogue engagement (whether GCs ranked dialogue as more one-sided/rigid or more interactive/conversational), time sufficiency (how adequate the GCs ranked the time allotted for the session), and interpreter-related factors (experience and relationship with interpreters; perceived ability and knowledge of how to work with interpreters) on GCs' perceived ability to contract in LD sessions. Forty-five GCs recruited from the NSGC listserv completed a 42-item survey exploring these topics through reflection on their most recent LD and language concordant (LC) sessions. The outcome measure of "perceived contracting success" was defined based on five practice-based competencies. Results were analyzed using Wilcoxon signed ranks tests and linear regressions and found that GCs' perceived (1) contracting success, (2) dialogue engagement, and (3) time sufficiency were significantly lower in LD sessions (p < 0.001 for all 3). Perceived contracting success in LD sessions had a positive relationship with both perceived dialogue engagement and perceived time sufficiency (r2 = 0.312, 0.103). Also, perceived dialogue engagement increased with higher perceived time sufficiency and trust in the interpreter (r2 = 0.235, 0.27). Our study is the first to quantitatively explore factors impacting perceived contracting success in LD GC sessions and suggests that LD may hinder communication and session tailoring. This highlights the importance of GCs being more intentional about having interactive dialogue with patients in LD sessions, considering allotting more time for LD sessions, and meeting with the interpreter prior to LD sessions to establish a trusting relationship.

PURPOSE:We describe strategies implemented across research centers of the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network to optimize engagement of participants and communities in cancer genomics research. We also present consensus definitions of engagement and engagement optimization, informed by our shared experiences in the Network. METHODS:Key informant interviews and a document review identified engagement and optimization strategies across PE-CGS research centers. Findings were synthesized using qualitative content analysis. Consensus on definitions of engagement and optimization were developed through iterative review by PE-CGS members. RESULTS:PE-CGS research centers adopted tailored strategies based on community needs and scientific gaps. Engagement strategies included community-based efforts (eg, advisory boards and newsletters) and participant-focused approaches (eg, enhanced informed consent and decision support tools). Optimization strategies leveraged scientific methods (eg, randomized controlled trials and surveys) to evaluate engagement. Engagement was described as the sustained and meaningful interactions between researchers, participants, and communities. Optimization was described as the application of scientific methods to refine and improve engagement and research processes and outcomes. CONCLUSION:Engagement and optimization strategies have informed research planning, conduct, and dissemination across PE-CGS. These approaches and definitions provide a foundation for developing evidence-based practices to strengthen participant and community involvement in cancer genomics research.

There are disparities in knowledge and awareness about colorectal (CRC) prevention and genetic testing among diverse communities in Los Angeles County (LAC). To address this, we trained a workforce of 42 community health workers (CoGENES) specialized in CRC prevention through a train-the-trainer program. We present preliminary results of a randomized controlled trial (RCT) to evaluate the impact of materials and training delivered by CoGENES as part of a NCI funded PE-CGS network program at USC. A two-armed, single blinded RCT was launched in August 2024, with recruitment ongoing. All participants are at least 18 years of age and residents of LAC. The intervention includes the delivery of an educational session by trained CoGENES and an a priori developed educational handbook. The control group receives standard CRC and genetic testing materials. Data on demographics, acculturation, cultural values and fatalism, health literacy, numeracy, generalized self-efficacy (GSE), genomic knowledge, cancer prevention behaviors and attitudes, are collected at baseline with validated or team-developed surveys. Follow-up surveys at 6-8 weeks and 6-months after intervention receipt evaluate changes in GSE, genomic knowledge, and cancer prevention behaviors. To date, 96 participants (mean age = 49.3; SD = 13.4) have been recruited, with 61 randomly assigned to the intervention arm, and 35 to the control arm. No statistically significant differences were found at baseline between the two groups. Most participants were female (85%), Mexican (67%), Catholic (62%), married (51%), had completed at least 11th grade (53%), homemakers (35%), and spoke mostly or only Spanish (71%). Family, and religion were ranked the highest among their values. Half of the participants consumed whole grains at least three times a week and had a median intake of fruits (1 cup/day) and vegetables (1 cup/day), below current recommendations. Moreover, 31% of participants consumed at least 4 portions of red meat, and 44% ate processed meat at least once a week. At least 80% of participants reported that they were “very willing” to increase intake of fruits and vegetables and reduce consumption of red/processed meat. Interim analyses of the subset of participants with 6-8 weeks follow-up data showed a statistically significant increase in the mean difference of correct answers (diff = 4.1; 95% CI = 1.8-6.3), and a decrease in the number of times participants selected the option “don’t know” (diff = -5.5; 95% CI = -8.9, -2.2) for the cancer genetic knowledge score in the intervention arm, while no change was reported in the control arm. We present preliminary evidence that deploying CRC prevention trained educators in a community setting, may improve colorectal cancer genetic knowledge, and highlights opportunities and willingness to improve lifestyle and dietary patterns to reduce CRC incidence. Janet Rodriguez, Bianca Rosales, Joel Sanchez Mendez, Diego Alvarez, Charité Ricker, Heinz-Josef Lenz, John Carpten, Lourdes Baezconde Garbanati, Mariana Stern. Experiences and preliminary results of a community-based randomized controlled trial to raise colorectal cancer awareness: Findings from the Community Genetic Navigation Engagement Specialist (CoGENES) program [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A158.

Colorectal cancer is a leading contributor to cancer-related mortality and health disparities within the Hispanic and Latino community. To uncover the biological and genetic factors underlying these inequities, we conducted an analysis of key colorectal cancer molecular characteristics, focusing on somatic alterations, gene expression and genetic similarity (NASEM's term for genetic ancestry). As part of the Cancer Moonshot PE-CGS network, we obtained and performed a comprehensive genome-scale analysis of 131 primary CRC Tumor/Normal samples within the Hispanic and Latino population from the Los Angeles area. For comparison, we analyzed 3, 920 Non-Hispanic White (NHW) samples obtained from public databases, including AACR-GENIE. Our methodology included DNA exome sequencing to evaluate somatic mutations, somatic copy number alterations, and genetic similarity, as well as RNA sequencing to investigate differential gene expression, cellular pathways, and gene fusions. Insights from Hispanic and Latino samples were systematically compared with those derived from NHW cohorts. In alignment with the NASEM report and terminology, we adhered to best practices for the use of race, ethnicity, genetic ancestry, and other population descriptors in genetics and genomics research. Our analysis revealed distinct genetic similarity patterns, with a notable prevalence of Peruvian-from-Lima-like (1KG-PEL-like) genetic similarity, as defined by the 1000 Genomes Project. These patterns correlated with microsatellite stability (MSI) status, age at diagnosis, and tumor location. Significant mutations were identified in key colorectal cancer genes, including APC, TP53, and KRAS. Comparative analyses highlighted CRC-related genes with significant differences between Hispanic and Latino samples and NHW cohorts. Drug-targetable amplifications were also identified, while gene fusion analyses uncovered targetable genes such as ALK, FGFR1, RAF1, and PTPRK. Notably, PTPRK was observed in samples with the highest 1KG-PEL-like genetic similarity proportions. This study advances the molecular profiling of colorectal cancer in Hispanics and Latinos, addressing an underrepresented population in cancer research. As one of the first Cancer Moonshot projects focused on CRC in Hispanics and Latinos with a substantial sample size and among the pioneering efforts to utilize multi-omics for molecular characterization, it sets a significant precedent. Genetic similarity is identified as a critical factor in colorectal carcinogenesis, providing essential insights into the biological drivers of cancer health disparities. By establishing a comprehensive framework for analyzing this underserved group, this research lays the groundwork for future studies, fostering advancements in precision medicine and supporting the development of tailored therapeutic strategies. Brigette Waldrup, Francisco G. Carranza, Yuxin Jin, Yonatan Amzaleg, Mackenzie Postel, David W. Craig, John D. Carpten, Boudoir Salhia, Charite N. Ricker, Julie O. Culver, Carmen E. Chavez, Mariana C. Stern, Lourdes Baezconde-Garbanati, Heinz-Josef Lenz, Enrique I. Velazquez-Villarreal. Comprehensive multi-omics analysis of colorectal cancer tumors in diverse populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1128.

Germline sequencing should be integrated with somatic testing of cancers to provide a comprehensive genetic assessment of disease.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases, or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 ( online only) for more. PURPOSE To guide use of multigene panels for germline genetic testing for patients with cancer. METHODS An ASCO Expert Panel convened to develop recommendations on the basis of a systematic review of guidelines, consensus statements, and studies of germline and somatic genetic testing. RESULTS Fifty-two guidelines and consensus statements met eligibility criteria for the primary search; 14 studies were identified for Clinical Question 4. RECOMMENDATIONS Patients should have a family history taken and recorded that includes details of cancers in first- and second-degree relatives and the patient's ethnicity. When more than one gene is relevant based on personal and/or family history, multigene panel testing should be offered. When considering what genes to include in the panel, the minimal panel should include the more strongly recommended genes from Table 1 and may include those less strongly recommended. A broader panel may be ordered when the potential benefits are clearly identified, and the potential harms from uncertain results should be mitigated. Patients who meet criteria for germline genetic testing should be offered germline testing regardless of results from tumor testing. Patients who would not normally be offered germline genetic testing based on personal and/or family history criteria but who have a pathogenic or likely pathogenic variant identified by tumor testing in a gene listed in Table 2 under the outlined circumstances should be offered germline testing. Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines .

Abstract Introduction: There is a lack of culturally sensitive materials to educate the Hispanic/Latino/a/x (H/L) community on colorectal cancer (CRC), which is the second and third leading cause of cancer deaths among H/L men and women in the United States, respectively. For these reasons, an Educational Tool Kit was created for the Community Genetic Navigation Specialists (CoGENEs) program at the Center for Optimizing Engagement of Hispanic Colorectal Cancer Patients in Cancer Genomic Characterization Studies (COPECC) at the University of Southern California (USC). CoGENES is a train the trainer program geared towards the development of a local workforce of trained community engagement specialists, promotores de salud (community health workers) that will act as liaison agents to increase knowledge and create community awareness on genetic research, clinical genetic testing, counseling, biospecimen donation and participation in clinical trials for H/Ls CRC patients, and community at large. Methods: The Tool Kit consisted of a newly developed educational handbook focused on CRC prevention, genetics, counseling, tumor testing, and patient navigation, as well as existing materials with resources for CRC and counseling. To test the handbook, five focus groups in Spanish/English were conducted with 44 participants, recruited via community agencies/clinics serving Los Angeles. Optimization probes focused on readability, knowledge, acceptability, barriers, and recommended changes. Content analysis was conducted with focus group transcripts to inform how to optimize the handbook. A Materials Review Optimization Scorecard was developed to evaluate materials on content, literacy, graphics, layout and typography, learning, stimulation and motivation, and cultural and language appropriateness. Fifteen pieces in the handbook were each rated by three community health workers. A final suitability score was calculated for each piece. Results: Overall, the materials were well received, and participants understood the overall main message of the materials. Feedback included refining terminology, providing additional headings and subtitles, and clarifying images to optimize the illustration of mutations. Final suitability scores from community health educators ranged from 80 to 99% for all materials, translating into “superior materials.” Conclusion: Overall materials were well received, and they were rated as “superior materials.” Participants’ feedback from CoGENES is shared with the Engagement Optimization Unit (EOU) and Patient Engagement Unit (PEU) to optimize ongoing education and research at COPECC. The MR-OS tool will be shared with other PEU’s at other center’s to encourage it use when developing educational materials. Citation Format: Yaneth L. Rodriguez, Janet Rodriguez, Charité Ricker, Julie Culver, Daisy Hernandez, Natalia Guierrez, Yvonne Cardona, Rosa Barahona, Bianca Rosales, Mariana Stern, Lourdes A. Baezconde-Garbanati. Testing of an educational tool kit for the Community Genetic Navigation Engagement Specialists, COGENES, Training Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2159.

This cross-sectional survey study explores ongoing initiatives to foster diversity and inclusivity within the field of genetic counseling, specifically focusing on opportunities within graduate programs for students to enhance language and counseling skills in Spanish, thereby fostering language concordance in genetic counseling settings. With a response rate of 44.8% (26/58) across genetic counseling graduate programs, our study provides an overview of educational offerings in Spanish, encompassing patient-facing, non-patient-facing, and combined opportunities. Of the programs that completed the survey, 73.1% (19/26) offer Spanish language opportunities. Several perceived benefits were identified by those that offer opportunities, including fostering cultural humility and diversity within the field, increasing awareness and accessibility of genetic counseling services, and facilitating involvement in research within minority groups. The information gathered from this study can be a resource for graduate programs seeking insights into effective strategies to incorporate Spanish language opportunities. Additionally, these results may also serve as a source of inspiration for students who want to apply their Spanish language skills in their training and future careers. Lastly, we propose ideas to enhance and expand the training of bilingual genetic counseling students in Spanish.