Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations.

Ancestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic and genomic studies. Leveraging the Latino Colorectal Cancer Consortium, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer (128 Latino, 469 non-Latino) to map somatic mutational features by ethnicity and genetic ancestry. Global proportions of African, East Asian, European, and Native American ancestries were estimated using ADMIXTURE. Associations between global genetic ancestry and somatic mutational features across genes were examined using logistic regression. TP53 , APC , and KRAS were the most recurrently mutated genes. Compared to non-Latino individuals, tumors from Latino individuals had fewer KRAS (OR=0.64, 95%CI=0.41-0.97, p=0.037) and PIK3CA mutations (OR=0.55, 95%CI=0.31-0.98, p=0.043). Genetic ancestry was associated with presence of somatic mutations in 39 genes (FDR-adjusted LRT p<0.05). Among these genes, a 10% increase in African ancestry was associated with significantly higher odds of mutation in KNCN (OR=1.34, 95%CI=1.09-1.66, p=5.74×10 -3 ) and TMEM184B (OR=1.53, 95%CI=1.10-2.12, p=0.011). Among RMGs, we found evidence of association between genetic ancestry and mutation status in CDC27 (LRT p=0.0084) and between SMAD2 mutation status and AFR ancestry (OR=1.14, 95%CI=1.00-1.30, p=0.046). Ancestry was not associated with tumor mutational burden. Individuals with above-average Native American ancestry had a lower frequency of microsatellite instable (MSI-H) vs microsatellite stable tumors (OR=0.45, 95%CI=0.21-0.99, p=0.048). Our findings provide new knowledge about the relationship between ancestral haplotypes and somatic mutational profiles that may be useful in developing precision medicine approaches and provide additional insight into genomic contributions to cancer disparities. Significance: Our data in ancestrally diverse populations adds essential information to characterize mutational features in the colorectal cancer genome. These results will help enhance equity in the development of precision medicine strategies.

Social network analysis of the CaRE2 health equity center: Team science in full display.

Cancer health disparities that exist in the Black or African American and Hispanic or Latino/x communities are scientific challenges, yet there are limited team science approaches to mitigate these challenges. This article's purpose is to evaluate the team science collaborations of the National Institutes of Health-funded Florida-California Cancer Research, Education & Engagement (CaRE2 ) Center partnership underscoring the inclusion of multidisciplinary team members and future under-represented minority (URM) cancer researchers. To understand our collaborative efforts, we conducted a social network analysis (SNA) of the CaRE2 Center partnership among University of Florida, Florida A&M University, and University of Southern California with data collected via the dimensions.ai application programming interface. We downloaded metadata for all publications associated with dimensions.ai IDs. The CaRE2 collaboration network increased over time as evidenced by accruing more external collaborators and more publishing of collaborative works. Degree centrality of key personnel was stable in each wave of the networks. CaRE2 key personnel averaged a total of 60.8 collaborators in 2018-2019 (SD = 57.4, minimum = 3, maximum = 221), and 65.8 collaborators in 2020-2021 (SD = 56.06, minimum = 4, maximum = 222). Betweenness was largely stable across all groups and waves. We observed a steady decline in transitivity, the probability that a pair of CaRE2 co-authors shared a third co-author, from 0.74 in 2018 to 0.47 in 2022. The SNA findings suggest that the CaRE2 Center partnership's publications show growth in team science collaborations with the inclusion of multidisciplinary team members from the three partner institutions and future URM cancer researchers who were mentored as trainees and early-stage investigators.

Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE2 Summer Cancer Research Education and Training Program.

In our previous publication, we reported a framework to develop an undergraduate cancer research training program at Florida A&M University (FAMU) under the umbrella of the Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center activity by harnessing the resources available at FAMU, the University of Florida (UF), and the University of Southern California (USC) Cancer Centers. The implementation of the CaRE2 face-to-face training platform was dramatically affected by the COVID-19 pandemic during the summer of 2020 and 2021 training periods. However, a concerted effort was made to restructure the face-to-face training model into virtual and hybrid training methods to maintain the continuity of the program during the pandemic. This article compared the three methods to identify the best platform for training URM students in cancer disparity research. The program's effectiveness was measured through motivation, experiences, and knowledge gained by trainees during and one year after the completion of the program. The results showed that the participants were highly positive in their feedback about the professional and academic values of the program. Although the virtual and hybrid methods experienced significant challenges during the pandemic, the hybrid training module offered an "above average" effectiveness in performance, like the face-to-face mentoring platform in mentoring URM students in cancer disparity research.

Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk.

BACKGROUND: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations. METHODS: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan. RESULTS: Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21-1.41; processed meat OR = 1.40; 95% CI = 1.20-1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29-1.46), 1.20 (95% CI = 1.12-1.27), and 1.07 (95% CI = 0.95-1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11-1.24), 1.35 (95% CI = 1.26-1.44), and 1.46 (95% CI = 1.26-1.69) for CC, CT, and TT, respectively. CONCLUSIONS: We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer. IMPACT: The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.

Associations Between Patient Experience With Care, Race and Ethnicity, and Receipt of CRC Treatment Among SEER-CAHPS Patients With Multiple Comorbidities.

BACKGROUND: Patients with colorectal cancer (CRC) and multiple comorbidities are less likely to receive guideline-concordant treatment (GCT), a disparity exacerbated by racial and ethnic disparities in GCT. Yet, positive patient experiences with care are associated with more appropriate care use. We investigated associations between patient experiences with care, race and ethnicity, and receipt of GCT for CRC among older adults with multiple comorbidities. METHODS: We used SEER-Consumer Assessment of Healthcare Providers and Systems (CAHPS) data to identify participants diagnosed with CRC from 2001 to 2017 at age ≥67 years with additional chronic conditions. Stage-specific GCT was identified following recommendations in the NCCN Guidelines for Colon and Rectal Cancer. Patient experiences with care were identified from CAHPS surveys. Multivariable log-binomial regression estimated associations between race and ethnicity and receipt of GCT by experiences with care. RESULTS: A total of 2,612 patients were included. Those reporting excellent experience with getting care quickly were 5% more likely to receive GCT than those reporting less-than-excellent experience (relative risk [RR], 1.05; 95% CI, 1.04-1.05). When reporting less-than-excellent experience with getting care quickly, non-Hispanic Black (NHB) patients were less likely than non-Hispanic White (NHW) patients to receive GCT (RR, 0.80; 99.38% CI, 0.78-0.82), yet NHB patients were more likely to receive GCT than NHW patients when reporting excellent experience (RR, 1.05; 99.38% CI, 1.02-1.09). When reporting less-than-excellent experience with getting needed care, Hispanic patients were less likely than NHW patients to receive GCT (RR, 0.91; 99.38% CI, 0.88-0.94), yet Hispanic patients were more likely to receive GCT than NHW patients when reporting excellent experience (RR, 1.06; 99.38% CI, 1.03-1.08). CONCLUSIONS: Although excellent patient experience among those with multiple comorbidities may not be strongly associated with receipt of GCT for CRC overall, improvements in experiences of accessing care among NHB and Hispanic patients with CRC and additional comorbidities may aid in mitigating racial and ethnic disparities in receipt of GCT.

Disparities among Black and Hispanic colorectal cancer patients: Findings from the California Cancer Registry.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in California and second among Hispanic/Latinx (H/L) males. Data from the California Cancer Registry were utilized to investigate the differential impact on CRC outcomes from demographic and clinical characteristics among non-Hispanic white (NHW), non-Hispanic Black (NHB), U.S. born (USB), and non-U.S. born (NUSB) H/L patients diagnosed during 1995-2020. METHODS: We identified 248,238 NHW, 28,433 NHB, and 62,747 H/L cases (32,402 NUSB and 30,345 USB). Disparities across groups were evaluated through case frequencies, odds ratios (OR) from logistic regression, and hazard ratios (HR) from Cox regression models. All statistical tests were two-sided. RESULTS: NHB patients showed a higher proportion of colon tumors (75.8%) than NHW (71.5%), whereas both NUSB (65.9%) and USB (66.9%) H/L cases had less (p < 0.001). In multivariate models, NUSB H/L cases were 15% more likely than NHW to have rectal cancer. Compared to NHW, NHB cases had the greatest proportion of Stage IV diagnoses (26.0%) and were more likely to die of CRC (multivariate HR = 1.12; 95% CI = 1.10-1.15). Instead, NUSB H/L patients were less likely to die of CRC (multivariate HR = 0.87; 95% CI = 0.85-0.89) whereas USB H/L did not differ from NHW. CONCLUSIONS: NHB and H/L cases have more adverse characteristics at diagnosis compared to NHW cases, with NHB cases being more likely to die from CRC. However, NUSB H/Ls cases showed better survival than NHW and US born H/L patients. These findings highlight the importance of considering nativity among H/L populations to understand cancer disparities.

Latin America and the Caribbean Code Against Cancer 1st edition: Tobacco and nicotine-related products, secondhand smoke, and alcohol and cancer.

Tobacco, secondhand smoke (SHS), and alcohol, all carcinogens, are leading preventable cancer risk factors in Latin America and the Caribbean (LAC). Since 2000, smoking and SHS exposure have significantly decreased in the region. Yet alcohol consumption remains high. The entry of nicotine-related products such as electronic cigarettes (e-cigs) threatens achievements made in tobacco control and chronic diseases prevention, including cancer. E-cigs use is likely associated with smoking initiation among adolescents who had never smoked and dual use with combustible tobacco products. Therefore, the LAC Code Against Cancer recommends to the public actions they can take to reduce their risk of cancer: 1. Don't smoke or use any type of tobacco. If you do, quitting is possible, with professional help if needed. Don't use e-cigarettes either, as they lead to tobacco use. 2. Make your home a smoke-free place. Respect and promote laws that ensure smoke-free spaces to protect our health. and 3. Avoid drinking alcoholic beverages. This helps prevent several types of cancer. The Code recommends to policymakers a package of cost-effective policies based on the MPOWER and SAFER to prevent cancer at the population level. It also recommends that primary care health professionals: 1. Ask all their patients and their families whether they smoke or vape, inform them about the harms of smoking and vaping, and promote tobacco and nicotine related products cessation strategies among users. 2. Inform about the harms of exposure to SHS, especially among children, and promote smoke-free environments, and 3. Prevent alcohol use by their patients and their families, use tools to assess use, intensity, and frequency, and apply brief counseling intervention to support alcohol abstinence in primary care.

Latin American and the Caribbean Code Against Cancer 1st edition: Weight, physical activity, diet, breastfeeding, and cancer.

In Latin America and the Caribbean a considerable proportion of the population have excess body weight, do not meet the recommendations of physical activity and healthy diet, and have suboptimal rates of breastfeeding. Excess body weight is associated with at least 15 cancer sites, physical activity protects against three cancers, with some evidence suggesting a protective effect for eight more cancer sites, and sedentary behavior probably increases the risk of five cancer sites. Fiber and wholegrains protect against colorectal cancer, high intake of fruits and vegetables could reduce the risk of aerodigestive cancers; processed and red meat increase the risk of colorectal cancer; and very hot beverages are associated with esophageal cancer. Moreover, sugar-sweetened beverages and ultra-processed foods are a convincing cause for excess body weight, increasing cancer risk through this pathway, with some emerging evidence suggesting also direct pathways. Breastfeeding protects against breast cancer, and could protect against ovarian cancer. Taking this evidence into account, the Latin America and the Caribbean Code Against Cancer recommends the general public to maintain a healthy body weight, be physically active and limit sedentary behavior, eat a healthy diet (eat plenty of vegetables, fruits, wholegrains and legumes; avoid sugar-sweetened beverages and processed meat; and limit ultra-processed foods, red meat and very hot beverages), and breastfeed. Moreover, the Latin America and the Caribbean Code Against Cancer also includes a set of public policy recommendations for cancer prevention to inform policy makers and civil society about the need of policies to shape healthy environments and create opportunities to facilitate the adoption of the recommendations directed to the public.

Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

Cognitive Testing of PAIN Report It-Spanish in Monolingual Hispanic Adults.

BACKGROUND: A Spanish language computerized tool would facilitate cancer pain assessment and management for the underserved population of native Spanish speakers who do not speak or lack command of the English language. OBJECTIVE: Our aim was to identify Spanish-speaking adults' understanding and interpretation of the PAIN Report It-Spanish items and instructions as well as translation and technical issues. METHODS: In a cross-sectional study, 20 mostly monolingual Spanish-speaking adults engaged in 1.5- to 2-hour, audio-recorded cognitive interviews as they completed the multidimensional PAIN Report It-Spanish. Three bilingual researchers conducted content data analysis. RESULTS: Sixteen women and 4 men generally understood the translated text, but some had interpretation issues regarding the 0 to 10 number scale and understanding of the pain quality descriptors. Many participants found the program easy to complete, even when they had problems in some areas. Most participants welcomed the opportunity to report pain in their native language and appreciated research to help Hispanics with the management of their pain. CONCLUSION: PAIN Report It-Spanish is a valid tool to assess pain in a Spanish-speaking population. Improved orientation to the pain reporting tasks and alternate translations for several problematic/confusing Spanish words require additional study, especially among underrepresented black Hispanics and males. IMPLICATION FOR PRACTICE: Findings indicate that Spanish-speaking adults (1) easily use a body outline to report their pain location, (2) may use a 0 to 10 scale differently than other individuals, and (3) may have a limited repertoire of pain quality and pattern descriptors.

Training Community African American and Hispanic/Latino/a Advocates on Prostate Cancer (PCa): a Multicultural and Bicoastal Approach.

African American communities are disproportionately impacted by prostate cancer (PCa) compared to other racial/ethnic groups. Whereas the incidence of PCa in Hispanic/Latino men is lower than the incidence in non-Hispanic/Latino White men, Hispanic/Latino men are more likely to be diagnosed with PCa in late stages, and less likely to be knowledgeable about PCa, resulting in significant disparities. We developed, culturally adapted, translated, implemented, and evaluated a PCa Cancer Advocacy Training in African American and Hispanic/Latino/a communities. Culturally and language specific content for African American and Hispanic/Latino/a patients on PCa causes, risk factors, epidemiology, detection, diagnosis, and treatment were delivered through a workshop and simultaneously broadcasted in Spanish in Los Angeles County (n = 29) and in English in Tallahassee, FL (n = 9). Pre- and posttest surveys assessed impact. Pre vs post differences were statistically significant in knowledge (5.0 ± 1.6 vs 6.3 ± 1.1) and advocacy intentions (3.9 ± 0.9 vs 4.3 ± 0.8), on correctly identifying warning signs for PCa (50% vs 87%), intent to inform and educate about PCa within the next 3 months (69% vs 95%), to ensure that high-quality research is sensitive to the priorities of patients (63% vs 84%), to help increase patient recruitment, compliance, and retention for clinical trials within the next month (62% vs 84%), intent to engage in PCa patient education within the next 3 months (67% vs 92%), and in engaging in PCa community outreach within the next 3 months (67% vs 94%). There were no significant differences due to race/ethnicity. The Cancer Advocacy Training led to increased knowledge, awareness, and intention to engage in advocacy regarding PCa in the next 3 months. Results suggest that delivering culturally and language specific educational information increases engagement of Hispanic/Latino/a and African American patient/community advocates.

Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses.

BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09). DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.

Association of nativity with survival among adults with hepatocellular carcinoma.

INTRODUCTION: Immigrants comprise a considerable proportion of those diagnosed with hepatocellular carcinoma (HCC) in the United States. Nativity or birthplace affects incidence and risk factors for HCC, but little is known about its influence on survival after diagnosis. METHODS: We identified 51 533 adults with HCC with available birthplace in the California Cancer Registry between 1988 and 2017. HCC cases were categorized as foreign born or US born and stratified by mutually exclusive race and ethnicity groups. Primary outcome was all-cause mortality. Race and ethnicity-specific Cox regression propensity score-weighted models evaluated the relationship between nativity and death as well as region of birth among foreign-born patients. RESULTS: A total of 40% of all HCC cases were foreign born, and 92.2%, 45.2%, 9.1%, and 5.8% of Asian/Pacific Islander (API), Hispanic, White, and Black patients were foreign born, respectively. Five-year survival rates were higher in foreign-born patients compared with US-born patients: 12.9% vs 9.6% for White patients, 11.7% vs 9.8% for Hispanic patients, 12.8% vs 8.1% for Black patients, and 16.4% vs 12.4% for API patients. Nativity was associated with survival, with better survival in foreign-born patients: White patients: hazard ratio (HR) = 0.86 (95% confidence interval [CI] = 0.81 to 0.90), Hispanic patients: HR = 0.90 (95% CI = 0.86 to 0.93), Black patients: HR = 0.89 (95% CI = 0.76 to 1.05), and API patients: HR = 0.94 (95% CI = 0.88 to 1.00). Among foreign-born patients, lower mortality was observed in those from Central and South America compared with Mexico for Hispanic patients, East Asia compared with Southeast Asia for API patients, and East Europe and Greater Middle East compared with West/South/North Europe for White patients. CONCLUSION: Foreign-born patients with HCC have better survival than US-born patients. Further investigation into the mechanisms of this survival disparity by nativity is needed.

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility. OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry. DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. RESULTS AND LIMITATIONS: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4). CONCLUSIONS: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. PATIENT SUMMARY: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

Priorities to Promote Participant Engagement in the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network.

BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network's research. METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network's research priorities in participant engagement: (i) a brainstorming exercise to elicit potential priorities; (ii) a 2-day virtual meeting to discuss priorities; (iii) recommendations from the PE-CGS External Advisory Panel to refine priorities; and (iv) a virtual meeting to set priorities. RESULTS: Nearly 150 PE-CGS stakeholders engaged in the process. Five priorities were set: (i) tailor education and communication materials for participants throughout the research process; (ii) identify measures of participant engagement; (iii) identify optimal participant engagement strategies; (iv) understand cancer disparities in the context of cancer genomics research; and (v) personalize the return of genomics findings to participants. CONCLUSIONS: PE-CGS is pursuing these priorities to meaningfully engage diverse and underrepresented patients with cancer and posttreatment cancer survivors as participants in cancer genomics research and, subsequently, generate new discoveries. IMPACT: Data from PE-CGS will be shared with the broader scientific community in a manner consistent with participant informed consent and community agreement.

Adding a One Health approach to a research framework for minority health and health disparities.

The National Institute on Minority Health and Health Disparities (NIMHD) has developed a framework to guide and orient research into health disparities and minority health. The framework depicts different domains of influence (such as biological and behavioral) and different levels of influence (such as individual and interpersonal). Here, influenced by the "One Health" approach, we propose adding two new levels of influence - interspecies and planetary - to this framework to reflect the interconnected nature of human, animal, and environmental health. Extending the framework in this way will help researchers to create new avenues of inquiry and encourage multidisciplinary collaborations. We then use the One Health approach to discuss how the COVID-19 pandemic has exacerbated health disparities, and show how the expanded framework can be applied to research into health disparities related to antimicrobial resistance and obesity.

Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk.

BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

Cancer Epidemiology in Hispanic Populations: What Have We Learned and Where Do We Need to Make Progress?

The Hispanic/Latino(x) population (H/L) in the United States of America is heterogeneous and fast growing. Cancer is the number one cause of death among H/Ls, accounting for 21% of deaths. Whereas for the most common cancers, incidence rates are lower in H/Ls compared with non-H/L White (NHW) individuals, H/Ls have a higher incidence of liver, stomach, cervical, penile, and gallbladder cancers. H/L patients tend to be diagnosed at more advanced stages for breast, colorectal, prostate, and lung cancers, and melanoma compared with NHW individuals. Etiologic and cancer outcomes research among H/Ls lags other populations. In this review, we provide a summary of challenges, opportunities, and research priorities related to cancer etiology, cancer outcomes, and survivorship to make progress in addressing scientific gaps. Briefly, we prioritize the need for more research on determinants of obesity, nonalcoholic fatty liver disease and its progression to liver cancer, stomach and gallbladder cancers, and pediatric acute lymphoblastic leukemia. We emphasize the need to improve cancer screening, early detection of cancer, and survivorship care. We highlight critical resources needed to make progress in cancer epidemiologic studies among H/L populations, including the importance of training the next generation of cancer epidemiologists conducting research in H/Ls.