Cancer-related Mortality Research Articles

LncRNA HAR1A inhibits non-small cell lung cancer growth by downregulating c-MYC transcripts and facilitating its proteasomal degradation

Non-small cell lung cancer (NSCLC) is a primary cause of cancer-related mortality on a global scale. Research increasingly shows that long non-coding RNAs (lncRNAs) play crucial regulatory roles and serve as biomarkers for diagnosis, prognosis, therapy monitoring, and druggable targets in NSCLC. We previously identified HAR1A as a tumor-suppressing lncRNA in NSCLC, with its loss also observed in oral and hepatocellular carcinoma. This study aimed to expand the understanding of the functional role of HAR1A in NSCLC and uncover its underlying mechanisms. Our results demonstrated that elevating HAR1A levels impeded NSCLC cell proliferation and migration but promoted apoptosis, thereby boosting their susceptibility to cisplatin. Subsequently, we discovered that HAR1A enhanced cisplatin’s cytotoxicity in NSCLC cells by curbing adaptive autophagy through the downregulation of MYC. Further analysis revealed that HAR1A suppresses MYC by both lowering its transcript levels and promoting protein ubiquitination and degradation, thereby restricting tumor cell proliferation, migration, and adaptive autophagy. In exploring MYC’s targets, we observed that MYC upregulated the transcription of heat shock protein 90 alpha family class B member 1 (HSP90AB1/HSP90β) gene. Rescue experiments verified that HAR1A mitigated NSCLC cell proliferation and migration and induced apoptosis through the MYC/HSP90β axis. Finally, we confirmed that HAR1A overexpression increased cisplatin efficacy in nude mouse NSCLC xenograft models.In conclusion, the findings suggest that HAR1A could be a promising therapeutic target in treating NSCLC and biomarkers for predicting chemotherapy outcomes. This study provides new insights into the molecular mechanisms of chemoresistance in NSCLC and underscores the potential of lncRNA-based strategies in cancer therapy.

Black Tea Suppresses Invasiveness and Reverses TNF-α-Induced Invasiveness and Cell Stemness in Human Malignant Melanoma Cells.

Invasiveness and epithelial-mesenchymal transition (EMT) are main patterns of metastatic disease, which is the major cause cancer-related mortality in human malignant melanoma cells. Tea and its consumption extract are associated with a lower risk of several types of cancer and have anti-inflammatory and antioxidative biological effects. However, the anti-EMT and anti-cancer stemness effect of black tea ethanol extracts (BTEE) in human melanoma remain poorly understood. In this study, the effects of BTEE-reduced invasiveness, EMT, and cancer stemness were evaluated in human A 375 and A2058 melanoma cells. BTEE inhibited the activity of u-PA, migration, and invasiveness by repressing p-FAK signaling pathway. BTEE affected the EMT by downregulating the expression of β-catenin, N-cadherin, fibronectin, vimentin, and Twist-1. BTEE also reduced tumor necrosis factor-alpha (TNF-α)-induced invasiveness and cancer stemness characteristics in vitro. The growth of melanoma in nude mice xenograft model showed that BTEE suppressed A 375 tumor growth in vivo.

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.

Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection of Dkk2 -knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested Hepatocyte nuclear factor 4-alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region of Sox9 , a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers.

MicroRNAs in Lung Cancer Brain Metastasis.

Brain metastasis is a significant clinical challenge for patients with advanced lung cancer, occurring in about 20-40% of cases. Brain metastasis causes severe neurological symptoms, leading to a poor prognosis and contributing significantly to lung cancer-related mortality. However, the underlying molecular mechanism behind brain metastasis remains largely unknown. MicroRNAs (miRNAs) are small, non-coding RNAs linked to several aspects of cancer progression, including metastasis. In the context of lung cancer, significant research has shown the involvement of miRNAs in regulating critical pathways related to metastatic spread to the brain. This review summarizes the scientific evidence regarding the regulatory roles of intra- and extracellular miRNAs, which specifically drive the spread of lung cancer cells to the brain. It also revises the known molecular mechanisms of brain metastasis, focusing on those from lung cancer as the primary tumor to better understand the complex mechanisms underlying this regulation. Understanding these complex regulatory mechanisms holds promise for developing novel diagnostic biomarkers and potential therapeutic strategies in brain metastasis.

Relationship Between Serum Copper, Zinc Level and Tumour Aggressiveness in Invasive Cervical Cancer

<i>Background: </i>Cervical cancer, a leading cause of cancer-related morbidity and mortality, exhibits considerable variability in aggressiveness. The role of trace elements such as copper and zinc in influencing tumor behavior and progression has garnered attention. This study investigates the relationship between serum copper and zinc levels and tumor aggressiveness in invasive cervical cancer.<i> Methods:</i> A cross-sectional comparative study was conducted among 150 women with invasive cervical cancer attending the outpatient department and Colposcopy Clinic of the Department of Gynecological Oncology, BSMMU, Dhaka, from April 2022 to March 2023. Participants were divided into two groups based on tumor aggressiveness: Group 1 (less aggressive) and Group 2 (more aggressive), with 75 women in each group. Serum copper and zinc levels were measured and analyzed for differences between groups. <i>Result:</i> Serum copper levels were significantly higher in Group 2 (152.31 ± 41.81 µg/dL) compared to Group 1 (139.31 ± 25.52 µg/dL) with a p-value of 0.023. Conversely, serum zinc levels were significantly lower in Group 2 (55.24 ± 28.13 µg/dL) compared to Group 1 (66.29 ± 31.58 µg/dL) with a p-value of 0.025. The copper/zinc ratio was significantly higher in Group 2 (2.76 ± 1.20) compared to Group 1 (2.10 ± 1.00) with a p-value of <0.001. <i>Conclusion:</i> Elevated serum copper levels and copper/zinc ratio, along with decreased zinc levels, are associated with more aggressive cervical cancer. These findings suggest that trace element imbalances may serve as biomarkers for assessing tumor aggressiveness and could inform future therapeutic strategies.

3D cell culture models in research: applications to lung cancer pharmacology.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, necessitating innovative research methodologies to improve treatment outcomes and develop novel strategies. The advent of three-dimensional (3D) cell cultures has marked a significant advancement in lung cancer research, offering a more physiologically relevant model compared to traditional two-dimensional (2D) cultures. This review elucidates the various types of 3D cell culture models currently used in lung cancer pharmacology, including spheroids, organoids and engineered tissue models, having pivotal roles in enhancing our understanding of lung cancer biology, facilitating drug development, and advancing precision medicine. 3D cell culture systems mimic the complex spatial architecture and microenvironment of lung tumours, providing critical insights into the cellular and molecular mechanisms of tumour progression, metastasis and drug responses. Spheroids, derived from commercialized cell lines, effectively model the tumour microenvironment (TME), including the formation of hypoxic and nutrient gradients, crucial for evaluating the penetration and efficacy of anti-cancer therapeutics. Organoids and tumouroids, derived from primary tissues, recapitulate the heterogeneity of lung cancers and are instrumental in personalized medicine approaches, supporting the simulation of in vivo pharmacological responses in a patient-specific context. Moreover, these models have been co-cultured with various cell types and biomimicry extracellular matrix (ECM) components to further recapitulate the heterotypic cell-cell and cell-ECM interactions present within the lung TME. 3D cultures have been significantly contributing to the identification of novel therapeutic targets and the understanding of resistance mechanisms against conventional therapies. Therefore, this review summarizes the latest findings in drug research involving lung cancer 3D models, together with the common laboratory-based assays used to study drug effects. Additionally, the integration of 3D cell cultures into lung cancer drug development workflows and precision medicine is discussed. This integration is pivotal in accelerating the translation of laboratory findings into clinical applications, thereby advancing the landscape of lung cancer treatment. By closely mirroring human lung tumours, these models not only enhance our understanding of the disease but also pave the way for the development of more effective and personalized therapeutic strategies.

Abstract A040: Effects of food environment, income inequality, and racial segregation on obesity- related cancer mortality

Abstract BACKGROUND: Rural areas experience 7-12% higher risk of obesity-related cancer mortality compared to their urban counterparts. Complex interactions between social and structural factors in rural areas, combined with limited access to healthy foods and lower income, warrant further study to understand drivers of this disparity. Methods: County-level rates of age-adjusted obesity-related cancer mortality per 100,000 (2009-2020 were obtained from the Centers for Disease Control and Prevention’s Wide-Ranging ONline Data for Epidemiologic Research database. Based on data from the Food Environment Atlas, we calculated food swamp using the modified Retail Food Environment Index (mRFEI) as the ratio of fast-food restaurants and convenience stores to grocery and specialized food stores, supercenters, and farmers markets. Food swamp scores were then divided into quartiles. Next, we used Global G and local Gi statistics to identify the presence of spatial autocorrelation in food swamp and subsequently calculated a spatial moving average (SMA) across counties. Measures of economic segregation, racial segregation, and racialized economic segregation were calculated using the Index of Concentration at the Extremes (ICE) using population and demographic estimates from the 2005- 2009 American Community Survey. Larger values reflect concentrated extremes of disadvantage. Poisson regression was used to assess the impact of food swamp, urban-rural status, economic segregation, racial segregation, and racialized economic segregation on rates of obesity-related cancer mortality. Results: Among the 3014 counties included, median food swamp score was 3.6 (interquartile range=2.6-4.9), and counties in the 2nd, 3rd, and 4th quartiles for food swamp had 2%, 4%, and 6% higher rates (respectively) of obesity-related cancer mortality than those in the 1st quartile. Incidence rate ratios for the association of food swamp quartile with obesity-related cancer mortality were 1-3% smaller after control for food swamp SMA and for racialized economic Urban-rural differences in obesity-related cancer mortality varied with all ICE measures. Rural counties had 5% higher rates of obesity-related cancer mortality (IRR=1.05, 95%CI=1.04-1.06), even after controlling for food swamp and food swamp SMA, but there was no longer an association after controlling for economic segregation (IRR=0.99, 95%CI=0.98-1.00). Rural counties had 5% higher rates of obesity-related cancer mortality (IRR=1.05, 95%CI=1.04-1.07) when controlling for racial segregation and 2% higher rates when controlling for racialized economic segregation (IRR=1.02, 95%CI=1.01-1.03). Thus, we stratified our models by urban-rural status and found that each ICE measure had larger effects on obesity-related cancer mortality in rural counties than in urban. CONCLUSION: While food swamp is important, the socioeconomic environment of a county has a larger impact on obesity- related cancer mortality. Individuals may have access to healthy food stores, but whether they can afford the healthy food is more important. Citation Format: Elizabeth S. Davis, Sara Myers, Jeffrey A. Franks, Michael R. Poulson, Julie R. Palmer, Kelly M. Kenzik. Effects of food environment, income inequality, and racial segregation on obesity- related cancer mortality [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A040.

Abstract C139: Cancer related excess death and potential life years lost among Black Americans

Abstract Introduction: Cancer represents the second leading cause of death in the United States and disproportionately affects Black Americans. In recent years, cancer-related mortality rates have declined for both Black and White Americans. However, mortality rates and rate ratios alone are insufficient for characterizing the burden of cancer disparities between racial groups. Among the most prevalent cancers in the US, we evaluated trends in excess mortality and years of potential life lost between Black and White Americans. Methods: This was a serial cross-sectional study using US national level data from CDC Wonder between the years 1999-2020. We included White and non-Hispanic Black Americans with a cause of death from breast, prostate, lung, colon, bladder, or uterine cancer. We measured age-adjusted excess death as well as excess years of potential life lost for each cancer site among Black and White Americans, stratified by sex when applicable. Annual mortality rates for each cancer site were sourced from the CDC Cancer Statistic Data Visualization tool. Results: The age adjusted mortality rate for all cancers declined between 1999-2020 for Black (257.2 to 166.8 per 100,000) and White Americans (200.9 to 149.3 per 100,000). Site specific cancer mortality rates declined in Black and White Americans for breast, prostate, lung, colon, and bladder cancer, but increased for uterine cancer. Among the most prevalent cancer sites, there were a total of 115,43 excess deaths with 2,093,327 excess years potential life lost for Black men and 59,134 excess deaths with 1,508,052 excess years potential life lost for Black women over a 22-year period. The trend of annual excess death and years potential life lost has slowly increased for Black men with colon cancer as well as Black women with breast and uterine cancer. Annual excess death and years potential life lost in Black men with prostate cancer decreased until 2013 after which it has slowly increased. Conclusion: Despite declining mortality rates in most cancers in the United States, Black Americans still experience a staggering number of excess deaths and years potential life lost due to cancer. Furthermore, the discordance between declining mortality rates and increasing excess death or years potential life lost in breast, prostate, colon, and uterine cancer highlight that racial disparities in cancer care and outcomes are likely worsening among Black Americans. Action is needed to support interventions and organizations committed to addressing cancer health inequities among Black Americans. Citation Format: Daniel S. Carson, Navya Gunaje, Sarah K. Holt, Nana Frimpong, Jenney R. Lee, Liz Sage, Erika M Wolff, Yaw A. Nyame. Cancer related excess death and potential life years lost among Black Americans [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C139.

Abstract B083: Community-based knowledge-to-action translation to improve early detection of prostate cancer among Black individuals

Abstract Introduction: Black individuals have 70-80% higher incidence and 120% higher mortality from prostate cancer when compared to all other groups in the US. This is the largest racial disparity in cancer-related mortality in the US and has persisted over the last five decades despite improvements in the diagnosis and treatment of prostate cancer. Our previous work demonstrated that intensified screening practices could reduce prostate cancer mortality among Black individuals. Challenges impede the translation of these findings into real-world interventions and practices. The objective of this study was to design a patient-centered and culturally tailored knowledge toolkit to improve the knowledge and awareness of prostate-specific antigen (PSA) testing in Black individuals to facilitate informed shared-decision making between Black patients and primary care providers. Methods: Using a community-partnered participatory research approach, we convened a working group of Black prostate cancer survivors and community advocates, and clinicians, researchers, and health communications specialists. During monthly meetings, the working group followed Graham’s Knowledge-to-Action framework to synthesize information from: 1) peer-reviewed literature on the use of shared decision-making aids; 2) interviews conducted by our research team with Black individuals regarding barriers and facilitators to access PSA testing; and 3) community input on PSA testing and prostate cancer early detection. We then facilitated four iterative design sessions with the working group to develop recommendations for toolkit content, framing, and format. Results: With the working group, we designed a comprehensive set of resources to increase knowledge and awareness of PSA testing for early detection of prostate cancer among Black individuals. The design framework includes detailed recommendations on the content, framing, and format for resources contained in the toolkit. Recommendations encompass: 1) interactive web-based documents that cover comprehensive information about prostate cancer risk and screening; 2) printable shared decision-making documents that present evidence-based information about the use of PSA testing to guide conversations between Black individuals and their primary care providers; and 3) educational videos focused on prostate cancer fundamentals and dispelling common misconceptions about prostate cancer risk and screening, with content delivered by Black prostate cancer survivors and interviews with Black providers and prostate cancer researchers. Conclusion: This study addressed the need for a community-developed approach to increasing knowledge and awareness about prostate cancer screening and early detection in an accessible, culturally tailored, and accurate manner. We used a collaborative process that centered the experiences of Black prostate cancer survivors and advocates in the design of a toolkit that can facilitate decision-making discussions between Black individuals and their care providers for use of PSA testing for prostate cancer screening. Citation Format: Jenney R. Lee, Sung Min Kim, Yohali Burrola- Mendez, Dante' Morehead, Marty Chakoian, Michael Ware, Kojo Ward, Floyd Gossett, Vida Henderson, Patricia Egwuatu, Burcu Darst, John Masembe, Erika M. Wolff, Yaw A Nyame. Community-based knowledge-to-action translation to improve early detection of prostate cancer among Black individuals [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B083.

Abstract B118: “When people don’t look at you as human, then it’s down from there…”: Experiences of 2SLGBTQIA+ people treated for cancer and implications for research participation

Abstract Background: Recent U.S. estimates show 20 million+ people identify as two-spirit, lesbian, gay, bisexual, transgender, queer, intersex, or asexual (2SLGBTQIA+). Despite heightened risk factors for cancer, 2SLGBTQIA+ people are an underserved population and have rarely been included in cancer research. Further, cancer-related mortality and quality of life measures for this population remain unknown. The Elsie Study uses in-depth interviews to better understand the experiences of 2SLGBTQIA+ people who have been treated for cancer and explore recruitment considerations to improve their research participation. Methods: We conducted 60-90 minute one-on-one semi-structured interviews with 2SLGBTQIA+ adults who have been previously treated for cancer. We recruited participants through targeted creative advertising campaigns on dating apps (HER, Scruff, Jack’d, Grindr) and through community organizations, community events, and the study website. Questions explored cancer treatment experiences, intersectional identities and experiences, research participation decision-making, recruitment strategies, and trusted sources of information. We recorded, transcribed, and de-identified interviews, and used thematic approaches for qualitative analysis. Results: Between June 2023-June 2024, we completed 65 interviews with sexually diverse cisgender women (n=17), cisgender men (n=16), transgender women (n=11), transgender men (n=4), and nonbinary, gender-expansive, and two spirit people (n=17). Participants were located throughout the U.S. in rural and urban areas with differing levels of cancer treatment access, social support, and structural support. Participants were treated for many types of cancer, with the most common being breast, prostate, and blood cancers. Among the sample, 38.5% were American Indian or Alaska Native, African American, or Asian/Asian American, and 13.8% identified as Hispanic. Notably, racially/ethnically marginalized 2SLGBTQIA+ participants described the emotional toll of dehumanization and how it impacted their cancer care treatment as individuals with multiple marginalized identities. For example, one participant said “Although I’m going through this physical pain, it’s emotionally painful to have to explain myself and my identifications to people who don’t know and don’t want to know either… What’s the point?” Another participant said, “When people don’t look at you as human, then it’s down from there unfortunately."Most participants had not previously participated in health research, but all interviewees affirmed they wanted to know the results from the study and wanted to be notified about future research opportunities with our team. The use of dating apps and community organizations as recruitment methods was noted as novel and trustworthy. Conclusion: People of all genders and sexual orientations get cancer, and 2SLGBTQIA+ people represent an increasing number of oncology patients. It is imperative that the perspectives of 2SLGBTQIA+ people be considered in cancer care and cancer research. Citation Format: Alexandra M. Ecklund, Ben Weideman, Rhea Alley, Courtney Sarkin, B.R. Simon Rosser, G. Nic Rider. “When people don’t look at you as human, then it’s down from there…”: Experiences of 2SLGBTQIA+ people treated for cancer and implications for research participation [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B118.

Abstract C175: Implementing cervical cancer screening services in women living with HIV in Trinidad and Tobago

Abstract Background: Women constitute 50% of people living with HIV, and cervical cancer (CCA) is among the top cancers for incidence and mortality, in the Caribbean. Women living with HIV (WLWH) are more susceptible and vulnerable to cancer due to their immune-compromised status. There is a pressing need for clinic-based CCA prevention in WLWH. Objective: A preliminary quality improvement evaluation of pilot CCA screening (Pap smear) targeting WLWH in Trinidad and Tobago from July 2020 to September 2021. Methodology: The electronic health information system from a large clinic was used to abstract Pap testing data. No personal identifiers were collected from the system to protect the privacy of individuals and abide by Trinidad and Tobago’s data protection law. Evaluation of quality improvement of interventions approach was applied. Descriptive analyses were conducted using SPSS. Results: A total of 242 WLWH attended the women's clinic (WHC) from July 2020 to September 2021. The average age was 41.2 (age range: 20-72). Most (78.9%) reported sexual activity initiation between 15-29 years old, and 2 in 3 (66.1%) had sexual activity in the last 12 months. Among our participants, 67.8% were Afro-Caribbean, 20.7% were Mixed, and 5.8% were East Indian. The majority of WLWH completed at least secondary education (69.8%). Almost half were single (49.6%), and 59.5% were employed/self-employed. Additionally, 11.6% of patients reported a family history of CCA. The WHC provided Pap test to 91.7% of WLWH, 69.3% had normal Pap test results, 9.2% had abnormal Pap test results, and 0.4% were diagnosed with CCA in situ. Additionally, 8.6% found infections including Candida Albicans, Actinomyces, and Trichomoniasis. For those with abnormal Pap tests, timely follow-up care was provided to prevent further illnesses and cervical dysplasia. WLWH with cervical cancer in situ were scheduled/referred to treatments to prevent CCA progression. Discussion: A women’s clinic approach to CCA screening was successful in providing Pap tests and promoting timely diagnostic and therapeutic care to prevent CCA. We thus recommend an implementation and dissemination science approach to create strategies for adopting, implementing, sustaining and disseminating clinic-based CCA screening and HPV-related cancer prevention to reduce cancer-related morbidity and mortality among WLWH. Citation Format: Jonathan Edwards, Gaole Song, Selena Todd, Tessa Galindo, Sharon Soyer, Gregory Boyce, Kamilah Thomas-Purcell, Jarrett Sharlene, Diadrey-Ann Sealy, Kathy-Ann Pate-Robinson, Kimlin Ashing, Jeffrey Edwards, Nyla Lyons. Implementing cervical cancer screening services in women living with HIV in Trinidad and Tobago [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C175.

Abstract C174: Examining cervical cancer screening rates among women living with HIV in Kajiado County, Kenya

Abstract Background: Kenyan women are disproportionately affected by HIV than their male counterparts, with a prevalence 5.5% compared to men whose prevalence is 2.9%. Women living with HIV (WLHIV) are more susceptible to cancer, in particular HPV-related cancers due to their immune-compromised status. In response, Kenyan Health Ministry recommends that women living with HIV (WLWH) be screened for cervical cancer annually by either visual inspection with acetic acid (VIA) or visual inspection with Lugol’s iodine (VILI), cytology and testing for HPV once every two years. Objective: Examining the rate of cervical cancer screening among women living with HIV (WLWH) in Kajiado County in 2022. Methodology: The electronic health information system was used to abstract data for WLWH in Kajiado county with 57 antiretroviral (ART) facilities. However, our analysis accessed data from 38 facilities whose data is captured in the health information system. Authorized health care workers from the County were requested to abstract redacted data from the health information system. No personal identifiers were collected from the system as away of protecting the privacy of individuals and abiding with the Kenya’s data protection law. Authorization to access the county was obtained from the county’s department of health while ethical approval was obtained from Mount Kenya University’s Institutional Scientific and Ethics Review Committee. Results: In 2022, a total of 16,827 people living with HIV were enrolled for care at the 38 ART selected sites. 11,785 (70%) were women with an age range of 15 to 49 years. A total of 3342 WLWH, representing 28.36% of the target population, were screened by using VIA. Of those screened, 3240 (97%) tested negative, 78 (2.3%) had positive results while 24 (0.7%) had suspicious lesions. Conclusion: Our analysis shows low reach of cervical cancer screening with only 28.36% of the targeted women being screened in 2022. The only available testing method (VIA) is less robust as compared to cytology and HPV testing. Thus, cervical cancer screening is underutilized, and importantly the available screening suffers fromWe also found a gap in reporting of HPV testing in the county. We thus recommend implementation science with community engagement examining the barriers to cervical cancer screening and HPV testing as well as timely reporting from multistakeholder e.g., system, provider, patient, family and advocate perspectives. This multisectoral health system-services approach will better inform research, practice and policy for effective HPV-related cancer prevention and control to reduce cancer-related morbidity and mortality among WLWH,. Citation Format: Caren Kamau, MS, Alice Njoroge,MS, Francis Makokha,PhD, Kimlin Ashing,PhD. Examining cervical cancer screening rates among women living with HIV in Kajiado County, Kenya [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C174.

Abstract C176: Implementing HPV vaccination services in people living with HIV in Trinidad and Tobago: COVID-19 vaccination may have boosted HPV vaccination

Abstract Background: Globally, Caribbean countries are among the most heavily burdened by both HIV and cervical cancer (CCA). People living with HIV (PLWH) are more susceptible and vulnerable to cancer due to their immune-compromised status. There is a pressing need for clinic-based CCA prevention in PLWH. Objective: A preliminary quality improvement evaluation of the vaccination program targeting PLWH in Trinidad and Tobago from October 2018 to May 2024. Methodology: The electronic health information system from a large clinic was used to abstract HPV vaccination data. No personal identifiers were collected from the system to protect the privacy of individuals and abide by Trinidad and Tobago’s data protection law. Evaluation of quality improvement of interventions approach was applied. Descriptive analyses were conducted using SPSS. Results: A total of 5,615 PLWH were eligible to participate in the HPV Vaccination clinic from October 2018 to May 2024. The average age was 39.6 (age range: 18- 51); 51.4% were women and 48.6% were men. Most (81.7%) PLWH reported their sexual orientation was heterosexual. Among our participants, 62.4% were Afro-Caribbean, 18.6% were Mixed, and 7.4% were East Indian/Indian. The majority of PLWH completed at least secondary education (69.8%). Half were single (50.5%), and 42.1% were employed/self-employed. Among these HPV vaccine-eligible persons, 1,157 patients (20.6%) received HPV vaccines. For those who had received vaccines, 254 patients (22.0%) were vaccinated with at least 1dose of the HPV vaccine, 301 (26.0%) were vaccinated up to dose 2 HPV vaccine, and 602 (52.0%) were vaccinated up to dose 3 HPV vaccine. Importantly, of those who received the HPV vaccine, the rate of uptake varied for each year. The uptake of HPV vaccine from January to May 2024 was 10.5% and in 2023 it was 18.5%. The highest uptake was in 2021 which was 22.4% followed by that in 2022 which was 20.3%. Between 2018 and 2020, the uptakes were 13.7% for 2020, 12.1% for 2019, and 5.3% for 2018. Discussion: Overall, the HPV vaccination rate for PLWH was relatively low; only 1 in 5 was vaccinated. Still, we saw an interesting trend with the highest vaccination uptake during the peak years of COVID-19 vaccinations. Hence, our data suggest that the COVID-19 vaccination program may have boosted HPV vaccination. Given our lessons learned, our goal is to seek funding for an implementation and dissemination science approach for adopting, implementing, and sustaining clinic-based HPV-related cancer prevention by bundling services such as Pap-Testing, PSA testing and/or co-vaccination (e.g., flu, shingles) to improve reach and uptake towards reducing cancer-related morbidity and mortality among PLWH. Citation Format: Tessa Galindo, Jonathan Edwards, Gaole Song, Sharon Soyer, Selena Todd, Gregory Boyce, Kimlin Ashing, Jeffrey Edwards. Implementing HPV vaccination services in people living with HIV in Trinidad and Tobago: COVID-19 vaccination may have boosted HPV vaccination [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C176.

Abstract A069: Leading causes of death among Asian American individuals compared with Pacific Islander individuals in the United States, 2018-2020

Abstract Background: Asian American and Pacific Islander races are two distinct groups that continue to be aggregated in many large, national mortality statistics in the United States (US), which leads to structural biases encoded into databases and inaccurate health implications that may deprive Pacific Islander individuals from opportunities for interventions aimed at reducing health disparities. Examining mortality rates for disaggregated Asian American and Pacific Islander populations across all 50 states was not possible until 2018. We compared the leading causes of death between Asian American and Pacific Islander individuals in the US during 2018-2020, stratified by sex and age. Methods: Cause of death among non-Hispanic Asian American and Pacific Islander individuals aged ≥20 years who died during 2018-2020 were obtained from the US National Center for Health Statistics. Age-standardized all-cause mortality rates (MRs) and the 5 leading causes of death were reported per 100,000 person-years separately for Asian American and Pacific Islander individuals, by sex (female/male) and age (20-54/55-64/65-74/75- 84 years). MR ratios (MRRs) were calculated by comparing MRs among Pacific Islander with Asian American individuals (reference group), by sex and age. Results: During 2018-2020, 63,338 female and 85,601 male deaths occurred among Asian American adults, and 4,116 female and 5,512 male deaths occurred among Pacific Islander adults. Compared to Asian American individuals, all-cause mortality was higher for Pacific Islander females (MRR=2.50,95%CI=2.43-2.59) and males (MRR=2.10,95%CI=2.04-2.16). Cancer was the leading cause of death for Asian American (MR=93.8) and Pacific Islander females (MR=181.6) and second for Asian American (MR=100.4) and Pacific Islander males (MR=185.2) after heart disease. Death rates for leading causes were substantially higher for Pacific Islander compared to Asian American females: cancer (MRR=1.93,95%CI=1.82-2.06), heart disease (MRR=3.18,95%CI=2.95-3.42), stroke (MRR=2.41,95%CI=2.13-2.73), diabetes (MRR=4.03,95%CI=3.55-4.56), and COVID-19 (MRR=2.60,95%CI=2.25-3.01) and for Pacific Islander compared to Asian American males: heart disease (MRR=2.56,95%CI=2.42-2.71), cancer (MRR=1.52,95%CI=1.42-1.62, diabetes (MRR=3.14,95%CI=2.81-3.50), accidental death (MRR=2.60,95%CI=2.33-2.88), and COVID-19 (MRR=2.04,95%CI=1.82-2.27). The largest relative cancer mortality rate disparity occurred in those aged 20-54 years and declined with older age among women (MRR range=1.37-2.67) and men (MRR range=1.16-2.26). Conclusion: Cancer was among the leading cause of death for both Asian American and Pacific Islander individuals, but cancer mortality rates were twice as high among Pacific Islander women and men compared to Asian American women and men. These disparities persisted among Pacific Islander individuals for nearly all leading causes of death, regardless of sex and age, underscoring the need to disaggregate Pacific Islander from Asian American race data to improve tailored health equity-focused interventions. Citation Format: Jacqueline B. Vo, Jazmyn L Bess, Kekoa Taparra, Paloma R. Mitra, Amy Berrington de Gonzalez, Neal D. Freedman, Meredith S. Shiels, Jaimie Z. Shing. Leading causes of death among Asian American individuals compared with Pacific Islander individuals in the United States, 2018-2020 [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A069.

Abstract C106: Enhanced characterization of molecular attributes through multi-omics analysis and comprehensive evaluation of global and local genomic ancestry in colorectal cancer among Hispanic-Latinos

Abstract Introduction: Colorectal cancer (CRC) remains a significant public health challenge, representing the second leading cause of cancer-related mortality in the United States. Although mortality rates have generally decreased, the Hispanic/Latino (H/L) population in the Los Angeles area still experiences mortality rates up to 20% higher than those of their Caucasian American counterparts. Additionally, they are often diagnosed at a younger age and with more advanced disease stages, highlighting significant disparities in CRC outcomes. Currently, there are limited studies integrating clinical and multi-omics data from H/L populations, which are crucial for understanding the implications of colorectal tumorigenesis and addressing these disparities effectively. Methods: Clinical and genomic sequencing data were obtained from 60 primary CRC Tumor/Normal (T/N) samples within the Hispanic/Latino (H/L) population in the Los Angeles area through the PE-CGS network. For comparison, we analyzed 3,578 samples from non-Hispanic Whites (NHW) obtained from public databases. Additionally, we retrieved three CRC samples with spatial transcriptomic (ST) data from the 10xGenomics database. Using Whole Exome and RNA sequencing data, we performed somatic mutations, somatic copy number alterations (SCNAs), differential gene expression, cellular pathways, gene fusions, and global & local genomic ancestry analyses. The ST data underwent analysis utilizing newly released bioinformatics tools. Clinical and genomic data were integrated. Results: In these studies, distinct Amerindian (AMR) genomic ancestry proportion, age at diagnosis, and tumor localization patterns were observed, alongside significant mutations in key genes such as APC, TP53, and KRAS. The studies revealed evident cancer heterogeneity, influenced by factors such as mutation type, microsatellite instability, tumor subsite, and ethnicity. Additionally, several previously well-defined SCNAs were detected in the majority of tumors. Comparative analysis of gene expression and cellular pathways between H/L and NHW samples revealed distinct patterns. Furthermore, we identified gene fusions that potentially contribute to oncogenic activity in CRC. Ancestry analysis pointed to a predominant AMR ancestry. Notably, distinct associations of genetic ancestry with CRC tumor clinicopathological characteristics were identified. ST analysis delineated separate cancer, immune, and stroma components within the tumors. Conclusion: Our research has explored the molecular profiling of CRC tumors in H/L patients, providing crucial insights into the characterization of CRC tumors at the DNA and RNA levels, as well as the complex clinical and genomic diversity within our target population. Additionally, it offers valuable insights into the heterogeneity of CRC tumors and the tumor microenvironment. These findings establish the groundwork for subsequent projects, potentially leading to precision medicine approaches. Citation Format: Enrique I. Velazquez-Villarreal, Brigette Waldrup, Yonatan Amzaleg, Yuxin Jin, Mackenzie Postel, Donna Loza, Serina Ovalle, Elizabeth Quino, Carmen Chavez, Julie Culver, Mariana C. Stern, Heinz-Josef Lenz, David W. Craig, John D. Carpten. Enhanced characterization of molecular attributes through multi-omics analysis and comprehensive evaluation of global and local genomic ancestry in colorectal cancer among Hispanic-Latinos [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C106.

Abstract A034: DNA repair capacity in metastatic castration-resistant prostate cancer patients using lymphocytes as surrogate markers

Abstract Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men from the United States (US) and Puerto Rico (PR). In 2024, around 35,250 PCa-related deaths will occur in the US, making PCa the second leading cause of cancer-related mortality in men in the US. In Puerto Rican men, PCa represents the first cause of cancer incidence (38%) and mortality (19%). Metastatic castrate-resistant prostate cancer (mCRPC) remains among the most frequent causes of cancer-related mortality in males. Patients with mCRPC become progressively resistant to androgen deprivation therapy, and the median survival for these patients is around two years. Ortiz-Sanchez et al. (2022) previously reported that the nucleotide excision repair (NER) pathway is dysregulated in the lymphocytes from patients with indolent and aggressive PCa; nevertheless, mCRPC cases were not included in the study design. Therefore, this pilot study aimed to evaluate the DNA repair capacity (DRC) in Puerto Rican men with and without mCRPC through the CometChip assay using lymphocytes as surrogate markers. Variations in mean DRC values were expected among the study groups. DRC measurements through the NER pathway were performed in a cohort of 96 participants, including PCa cases (n=71) and controls (n=25). The mean DRC value for the control group was 17.63%, and for the cases, it was 7.90%. When comparing mCRPC (n=16), non-mCRPC (n=55), and controls, significant differences were observed between the controls and each cancer group. However, no significant differences were found between PCa cases stratified by disease aggressiveness. Currently, we are evaluating the functionality of the homologous recombination repair pathway to gain additional insights into the role of DRC in PCa. Our results represent the first effort to apply a phenotypic assay to evaluate the overall DRC in mCRPC. This may improve patient diagnosis and patient stratification in terms of disease progression. Citation Format: Jaime Matta, Jarline Encarnación-Medina, Gilberto Ruiz-Deya, Valerie Rodriguez-Baez, Carmen Ortiz-Sanchez. DNA repair capacity in metastatic castration-resistant prostate cancer patients using lymphocytes as surrogate markers [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A034.

Abstract C171: Identifying cancer driver mutation signatures in lung adenocarcinoma from Black/African American individuals: Addressing cancer health disparities

Abstract Lung cancer remains the leading cause of cancer-related mortality globally and continues to contribute significantly to cancer health disparities. Black/African American (B/AA) men exhibit a higher risk of lung cancer compared to White men; B/AA individuals also exhibit lower 5-year survival and stage-specific survival rates than White subjects. Biological factors, including genetic differences in cancer driver mutation, may influence this disparity. Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer across all ethnic groups, including B/AA individuals. Our study aims to characterize the main driver and co-mutation signatures of LUAD in B/AA individuals, who are significantly underrepresented in current mutational studies. We hypothesize that B/AA individuals will have a unique repertoire of cancer driver genes, which could contribute to genetic differences and response to targeted therapies compared to LUAD of White subjects. We are obtaining 100 de-identified archival formalin-fixed, paraffin-embedded (FFPE) LUAD samples from B/AA subjects from cancer registries in Florida and California. Extraction of DNA from the FFPE samples is in progress, and samples have been sent for whole exome sequencing (WES) and ancestry determination. This data will then be analyzed and compared with known LUAD mutation profiles from other ethnicities. Identification of cancer driver mutations will then inform the development of in vitro models for therapeutic testing. To date, the limited information on cancer driver genes in LUAD from B/AA subjects suggests that KRAS is the most common cancer driver gene, just like in LUAD from White subjects, and is found in ∼34% of cases. Therefore, we anticipate identifying KRAS mutations similar to this proportion based on the collection of previously published literature analyses. One key goal of this study is to obtain more information about the exact spectrum of KRAS mutations in LUAD from B/AA subjects. In addition, our work may unveil new variants of known cancer driver mutations such as KRAS, EGFR, BRAF, etc., and finally, “new” driver genes. Our efforts will address critical gaps in the understanding of lung cancer driver genes, a key step to developing personalized treatment of lung cancer and mitigating cancer health disparities between B/AA and White individuals. Supported by grants U54CA233396, U54CA233444, and U54CA233465 from the National Institutes of Health (NIH)/National Cancer Institute (NCI), the Norris Comprehensive Cancer Center core grant, award number P30CA014089 from the NIH/NCI, and by the Undergraduate Research Associates Program supported by the USC Provost. Citation Format: Davin Pan, Daniel J. Mullen, Colton Stensrud, Jose Aparicio, Christina M. Gobin, Sofia Lugo, Kweku Ofosu-Asante, Justin K. Mensah-Mamfo, Kyle R Phillips, Yong Huang, Nazarius S. Lamango, William D Wallace, Suhn K Rhie, Kristinanna M. Fredenburg, Ite A. Offringa. Identifying cancer driver mutation signatures in lung adenocarcinoma from Black/African American individuals: Addressing cancer health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C171.

Abstract C103: Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer

Abstract Colorectal cancer (CRC) is the most prevalent gastrointestinal cancer, the third most common malignancy and the second leading cause of cancer-related mortality worldwide. The American Cancer Society (ACS) estimates 152,810 new cases of colorectal cancer, with an estimated 53,010 deaths in 2024. Typically diagnosed in older adults, CRC incidence is rising among younger individuals, particularly in Hispanics (16.5%) compared to non-Hispanic whites (8.7%). Due to the lack of timely screenings in this ethnic group, further research is crucial to identify novel biomarkers and therapeutic targets for improved early detection and intervention. To accomplish this goal, we performed RNA-sequencing of Hispanic and non-Hispanic White (NHW) CRC tissues. The transcriptomic analysis revealed differential gene expression patterns in Hispanic and NHW populations when compared to respective normal adjacent tissues (NATs). We identified 3577 differentially expressed genes (DEGs) in Hispanic CRC samples and 2971 DEGs in NHW CRC samples, of which 1831 DEGs were unique to Hispanic. Based on the preliminary analysis we hypothesized that unique DEGs from the Hispanic population could help identify potential pathways contributing to CRC progression. Among these 1831 unique DEGs, many of the genes are associated with cholesterol and fatty acid synthesis pathway. The cholesterol biosynthesis pathway is a highly diverse and interconnected signaling pathway, playing essential roles in cellular function and systemic homeostasis. Its complexity and regulatory mechanisms make it a critical area of study in cancer. Studies indicate that Hispanics and African Americans with high cholesterol tend to have higher Body mass index (BMI) levels compared to Whites which has an increased risk of colorectal cancer. However, the role of cholesterol metabolism and fatty acid metabolism in CRC have not been studied from the Hispanic health disparities perspective. From the 1831 DEGs, we selected those in the cholesterol and fatty acid synthesis pathways with significant log2 fold changes (≤ -2 or ≥ +2) and adjusted p-values (FDR ≤ 0.05). Our bioinformatics analysis identified four key DEGs: LCN2, DHCR7, PCSK9 and SQLE. The expression levels of these genes were examined in Hispanic CRC vs. NHW CRC tissue samples using qRT-PCR. Elevated expression of LCN2 and SQLE was observed in late-stage Hispanic CRC tissues compared to NHW CRC tissues, while DHCR7 exhibited high expression in early-stage Hispanic CRC. On the other hand, PCSK9 showed low expression in both early and late stages of Hispanic CRC, suggesting potential ethnicity-specific molecular signatures in CRC progression. Moving forward, protein level studies and functional analysis of these DEGs in Hispanic CRC tissues and organoids will enhance our understanding of the role of cholesterol and fatty acid synthesis pathway proteins. Thus, elucidating novel molecular mechanisms underlying CRC progression could lead to identification of potential Hispanic specific biomarkers and therapeutic targets for early diagnosis and intervention. Citation Format: Somrita Roy, Soumya Nair, MD Zahirul Islam Khan, Sourav Roy. Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C103.

Oncologic Outcomes after Percutaneous Ablation for Colorectal Liver Metastases: An Updated Comprehensive Review.

Colorectal cancer is a major cause of cancer-related mortality, with liver metastases occurring in over a third of patients, and is correlated with poor prognosis. Despite surgical resection being the primary treatment option, only about 20% of patients qualify for surgery. Current guidelines recommend thermal ablation either alone or combined with surgery to treat limited hepatic metastases, provided that all visible disease can be effectively eradicated. Several ablation modalities, including radiofrequency ablation, microwave ablation, cryoablation, irreversible electroporation and histotripsy, are part of the percutaneous ablation armamentarium. Thermal ablation, including radiofrequency, microwave ablation and cryoablation, can offer local tumor control rates comparable to limited resection for selected tumors that can be ablated with margins. This review aims to encapsulate the current clinical evidence regarding the efficacy and oncologic outcomes after percutaneous ablation for the treatment of colorectal liver metastatic disease.

Association of periodontitis with all-cause and cause-specific mortality among individuals with depression: a population-based study

To detect the association between periodontitis and all-cause as well as cause-specific mortality rates among adults diagnosed with depression. Participants diagnosed with depression were selected from NHANES across three periods (1988—1994; 1999—2004; 2009—2014). Cox proportional hazards and Weibull accelerated failure time (AFT) models were utilized to calculate hazard ratios (HRs), time ratios (TRs), and their 95% confidence intervals (CIs) to evaluate the association between moderate-to-severe periodontitis and all-cause as well as cause-specific mortality among participants with depression. white blood counts and C-reactive protein were used to assess the mediating role of systemic inflammation. Among the 1,189 participants with a median follow-up of 9.25 years, 133 deaths were recorded. After adjusting for multiple variables, moderate-to-severe periodontitis was obvious associated with an increased risk of cancer-related mortality in individuals with depression (Cox: HR 3.22, 95% CI 1.51—6.83, P = 0.002; AFT: TR 0.70, 95% CI 0.52—0.94, P = 0.017). Neither WBC nor CRP significantly mediate the association between periodontitis and cancer-related mortality. The risk of cancer-related mortality rose with the severity of periodontitis (P for trend = 0.021). However, no association was observed between moderate-to-severe periodontitis and other kinds of mortality. Moderate-to-severe periodontitis is linked to an elevated risk of cancer-related mortality among adults diagnosed with depression, with the mortality risk increasing alongside the severity of periodontitis. No significant mediating effect of systemic inflammation was found in this association. These findings highlight the importance of addressing periodontal health in individuals with depression. By uncovering the association between periodontitis and mortality in this population, our study underscores the potential benefits of preventive dental care and periodontal treatment in reducing the risk of cancer-related mortality in individuals with depression.