Cancer Registry Research Articles

Linking local cancer registries and national death records: a crucial step for accurate survival data in Saudi Arabia

BackgroundThe absence of a link between cancer registries and governmental mortality databases in Saudi Arabia (SA) poses a significant challenge. This disconnect results in incomplete and inaccurate cancer registry survival data, which is crucial for precise survival estimates. While survival data could be updated through direct contact with cancer patients, their families, or physicians, the more accurate and effective method is through computerized linkage. Unfortunately, this method is not currently utilized in SA.ObjectiveThis research aims to assess the knowledge and opinion of the experts in the field of cancer on the importance of having a computerized linkage between cancer registries and Saudi Arabia’s National Death Registry, and secondly, to evaluate the effect of the currently used different follow-up methods on five-year survival estimates.MethodsThis study employed a cross-sectional, mixed-methods design. The qualitative component explored experts’ opinions on using record linkage to obtain survival data, assessed through a Likert-scale questionnaire. In the quantitative component, currently available methods to obtain survival data from healthcare systems were evaluated using survival analysis and compared to the active follow-up method. Survival analysis was performed using the Kaplan–Meier method. Survival probabilities were compared using the log-rank test.ResultsThe survey outcome revealed that 100% (n = 9) of the experts preferred the proposed computerized linkage method to update cancer survival data. The survival analysis using the healthcare system's mortality data without linkage to the National Death Registry results in an overestimated survival rate of 77.9% vs. 70.2%, with a P-value < 0.001.ConclusionThe study's findings underscore the limitations of the current system. The mortality data from the health systems alone cannot be relied upon, as they only report deaths within their system. To obtain accurate and complete data, trustworthy sources such as the National Death Registry must be utilized. The direct (active) follow-up, while effective, is a resource-intensive process that cannot be used for all cancer patients, even at the hospital level. Therefore, adopting the proposed computerized linkage is recommended.

Abstract 2332: Ductal carcinoma in situ: Potential to metastasize? A nationwide cancer registry-based study

Abstract Background: The current clinical paradigm around Ductal Carcinoma in Situ (DCIS) is that it consists of malignant cells confined to the breast ducts, and therefore cannot metastasize. Nonetheless, several studies have reported DCIS with metastasis in the sentinel lymph node (SN+). For accurate risk communication and management, we aimed to assess to what extent registered “metastatic spread” in DCIS could be explained by limitations in registration or missed invasive breast cancer at time of diagnosis. Methods: Data from the nationwide cancer registry and national pathology database on women diagnosed with DCIS SN+ in the Netherlands, spanning from 2005 to 2020, was curated and reviewed, taking into account their histories of prior DCIS, invasive breast cancer, or other malignancies. Cases were excluded from further analysis if pathology data indicated registration errors, DCIS mixed with other lesion types, or diagnostic uncertainties. Next, hematoxylin and eosin-stained tissue slides of eligible DCIS SN+ cases were independently reviewed by two pathologists to assess the presence of invasive breast cancer and SN status. Additional immunohistochemical staining (CK 5/6 or CK 8/18) was performed when findings were unclear. Inter-observer agreement was evaluated using the linearly weighted Kappa statistic. Results: A total of 30, 863 patients were identified with a DCIS diagnosis between 2005 and 2020, of which 16, 070 (52%) underwent SN biopsy according to cancer registry data. SN+ was registered in 454 (3 %) patients: 47 (10%) had macrometastases (&amp;gt;2 mm), 78 (17%) had micrometastases (&amp;gt;0.2 to &amp;lt;= 2 mm), and 329 (73%) were positive for isolated tumor cells (&amp;lt;= 0.2 mm). Out of the 454 registered DCIS SN+ cases, 273 (60%) were excluded from further investigation based on pathology data, including registration errors (n=44), DCIS mixed with other lesions (n=147), and diagnostic uncertainties (n=82). Tissue material of 46 (37%) out of 125 registered cases with macro- and micrometastases was reviewed. Observer variability in assessing the presence of invasive breast cancer was high (k= 0.14; 95% CI 0.08 - 0.34; p = 0.12) and additional CK 5/6 staining was requested for 38 cases. Two cases were classified as primary invasive breast cancer, 25 as pure DCIS, while 19 remained inconclusive, due to variation in tissue sections or suboptimal tissue quality. In six cases the SN was scored as negative by pathology revision, likely due to tissue section variability. Conclusions: Our study indicates that DCIS in itself has minimal to no metastatic potential. Ongoing clonality analysis of 9 cases with macrometastases aims to determine whether the SN metastases are clonally related to the DCIS lesions. Citation Format: Merle van Leeuwen, Sandra van den Belt- Dusebout, Petra Kristel, Lennart Mulder, Joyce Sanders, Carmen Vlahu, Esther H. Lips, Jelle Wesseling. Ductal carcinoma in situ: Potential to metastasize? A nationwide cancer registry-based study [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 2332.

Annual Report to the Nation on the Status of Cancer, featuring state-level statistics after the onset of the COVID-19 pandemic.

This report represents a collaborative effort by the major cancer surveillance organizations to present the definitive US statistics for cancer incidence and mortality. Cancer incidence data were obtained from population-based cancer registries funded by the Centers for Disease Control and Prevention and the National Cancer Institute and compiled by the North American Association of Central Cancer Registries. Cancer death data were obtained from the National Center for Health Statistics' National Vital Statistics System. Statistics are reported by cancer type, sex, race and ethnicity, and age. The potential impact of the coronavirus disease 2019 (COVID-19) pandemic on incidence was assessed by using state-level changes compared with previous years, the stringency of COVID-19 policy restrictions, the magnitude of COVID-19 death rates, and changes in the use of mammography. Overall cancer incidence rates per 100,000 were 500 among males and 437 among females. Excluding 2020, cancer incidence rates remained stable (2013-2021) among males and increased 0.3% per year on average (2003-2021) among females. The overall cancer death rate per 100,000 was 173 among males and 126 among females. Cancer death rates decreased by 1.5% per year (2018-2022), slowing from a previous 2.1% decline. Cancer incidence in 2020 declined from prepandemic levels for all demographic groups examined. However, the magnitude of decline was not strongly associated with the study's proxies for health care capacity, health care access, or COVID-19 policies. Overall cancer mortality declined over 20 years, even during the COVID-19 pandemic. Disruptions in health care use early in the pandemic resulted in incidence declines in 2020, but 2021 incidence returned to prepandemic levels.

Abstract 5814: Immune-related adverse effects in patients with autoimmune disorders treated with immune checkpoint inhibitors

Abstract Background: Immune checkpoint inhibitors (ICI) have tremendously improved outcomes for various cancers but can be associated with immune-related adverse effects (IrAE), which can affect multiple organ systems. For patients with pre-existing autoimmune diseases (AD), there is an added risk of exacerbating autoimmunity, either through a flare of prior IrAEs or the development of de novo IrAEs during ICI therapy. Clinical trials leading up to FDA approval of ICIs excluded patients with pre-existing AD, resulting in a lack of data on the specific risks faced by this patient population. Our study aims to assess whether patients with pre-existing AD are more likely to develop IrAEs when treated with ICIs, and if so, whether these IrAEs are more severe. Methodology: We conducted a retrospective chart review of all patients diagnosed with AD and received ICIs for treatment of a solid tumor malignancy within the Geisinger Health System from January 1, 2017, to December 31, 2023. We analyzed the occurrence, subtype, and severity (grade) of IrAEs based on the Common Terminology Criteria for Adverse Events (CTCAE). Additionally, we assessed steroid use, treatment discontinuation, and hospitalization rates. Results: A total of 250 patient charts were identified using the cancer registry, 105 of them were excluded due to the absence of a pre-existing AD. Of the 145 patients with a pre-existing AD, 59 (40.7%) developed an IrAE, and 21 (14.5%) developed a severe (grade 3/4) IrAE. Additionally, 44 (30.3%) patients required steroids for the treatment of IrAE, and 12 (8.3%) were hospitalized due to an IrAE. The most prevalent IrAEs were colitis, rash, hypothyroidism, transaminitis, and pneumonitis, which occurred in 52 (35%) cases; of these, 13 (8.9%) were severe (grade ¾). Discussion: When comparing our results to those of previous studies, we found that the rates and severity of IrAEs were higher in patients with pre-existing AD compared to historical data on patients without AD. A meta-analysis by de Velasco et al. of 21 studies reported an IrAE incidence of 28% for all grades and 5% for grades 3 and 4. Similarly, Silverstein et al. analyzed 3,137 patients treated with ICIs and found that 3.8% were hospitalized due to IrAEs. These significant differences underscore the need for multidisciplinary collaboration and heightened monitoring for IrAEs in patients with AD. Citation Format: Aseel Saadeh, Pragosh Saini, Favour Nelson, Sumera Khan, Christian Adonizio, Ahmad Hanif. Immune-related adverse effects in patients with autoimmune disorders treated with immune checkpoint inhibitors [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 5814.

Abstract 6420: Association between added sugar, glycemic index, glycemic load, soda consumption, and fiber intake with breast cancer risk

Abstract Background: Mexico has a high prevalence of dietary patterns rich in added sugars, low in fiber, and with frequent soda consumption. These factors are emerging contributors to chronic diseases, including breast cancer (BC). This study aimed to evaluate the associations of added sugar, glycemic index (GI), glycemic load (GL), soda consumption, and dietary fiber intake with BC incidence in Mexican women from the Mexican Teachers’ Cohort (MTC). Methods: This prospective cohort included 89, 879 women from 12 Mexican states, cancer-free at baseline, with dietary data collected via a validated food frequency questionnaire (2006-2008). Added sugar intake was categorized into four groups (≤26, 27-52, 53-78, ≥79 g/day), fiber intake into four categories (&amp;lt;25, 25-30, 30-35, ≥35 g/day), and soda consumption into five categories (≤0.5, 0.6-1.5, 1.6-2.5, 2.6-4.0, ≥4.1 servings/week). GI and GL were divided into quintiles. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for BC incidence, adjusting for socioeconomic status, reproductive history, physical activity, and dietary covariates. BC cases were identified through medical records and cancer registries until December 2019. Results: Over a median follow-up of 10.9 years, 1, 313 BC cases were identified. Median added sugar intake was 52 g/day (IQR: 36-77). Higher added sugar intake (53-78 g/day) was associated with a 27% increased BC risk (HR=1.27, 95% CI: 1.01-1.59), rising to 39% in premenopausal women (HR=1.39, 95% CI: 0.96-2.02). High GI was associated with increased BC risk in postmenopausal women (third quintile HR=1.57, 95% CI: 1.14-2.16), and high GL was linked to a 41% increased risk in premenopausal women (highest quintile HR=1.41, 95% CI: 1.01-1.96). Soda consumption emerged as a significant contributor to BC risk. Women consuming ≥4 servings/week had a 25% increased BC risk compared to ≤0.5 servings/week (HR=1.25, 95% CI: 1.00-1.56). Soda was the primary source of added sugars in the cohort. Fiber intake showed a protective trend. Compared to &amp;lt;25 g/day, women consuming ≥35 g/day had a 21% reduced BC risk (HR=0.79, 95% CI: 0.63-1.01). Multivariable adjustments consistently supported this association. Conclusions: High added sugar and soda consumption, alongside dietary patterns with high GI and GL, increase BC risk in Mexican women, particularly in premenopausal and postmenopausal subgroups. Increased fiber intake appears protective. Public health strategies should prioritize reducing soda and added sugar consumption and promoting dietary fiber to lower BC incidence in the Mexican population. Citation Format: Liliana Gomez-Flores-Ramos, Leticia Palma, Dalia Stern, Marion Brochier, Adrian Cortes-Valencia, Pabel Miranda-Aguirre, Patricia Pérez-Escobedo, Mauricio Hernandez-Avila, Martin Lajous. Association between added sugar, glycemic index, glycemic load, soda consumption, and fiber intake with breast cancer risk [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 6420.

Abstract 2047: Homologous recombination deficiency in lung cancer in the INSPIRE study

Abstract Introduction: Evaluating genomic signatures may improve prognostic information and outcomes for patients with lung cancer. Objective: To determine if homologous recombination deficiency (HRD) is associated with clinical features or overall survival in patients with lung cancer. Methods: This is a retrospective cohort study derived from City of Hope’s Implementing Next-Generation Sequencing for Precision Intervention and Risk Evaluation (INSPIRE) study. Study participants with histologically confirmed lung cancer and adequate tissue for comprehensive paired tumor-normal whole exome sequencing were eligible for analysis. 197 patients were sequenced, excluding 14 with rare histologies. Clinical and treatment variables were obtained from cancer registries and the electronic medical record and were recorded by experienced data curation and abstraction specialists. HRD scores were calculated using the scarHRD R package. Mutational signatures were analyzed using SigProfiler and SigEstimation. Associations between clinical variables and HRD status were measured using univariate and multivariate methods. Unsupervised analysis was performed to identify genes in HRD-high (sum score greater than or equal to 42) and HRD-low samples (sum score less than 42). Overall survival was quantified using non-parametric Kaplan-Meier statistics and multivariate Cox-proportional hazards models. Results: Of the 183 lung cancer samples analyzed, 63 (34.4%) samples were HRD-high. Of these, 43 had a TP53 alteration and 20 did not; 120 (65.6%) samples were HRD-low, 50 with a TP53 alteration and 70 without (OR 3.01 (95%CI 1.58, 5.72), p=0.0008). Conclusion: TP53 alterations were strongly associated with high HRD scores. Overall survival was improved in patients with HRD-high tumors treated with platinum therapy, although this difference did not reach statistical significance. Citation Format: Katherine G. Roth, Kevin J. McDonnell, Ernest Nadal, Joseph D. Bonner, Arman Seuylemezian, Suravi Nahar, Lawrence Shaktah, Jonathan Salazar, Sidney Lindsey, Xiaoyu Xia, Sara A. Byron, Jonathan J. Keats, Allen Mao, Adrien Larsen, Bryce Turner, Ravi Salgia, Stacy W. Gray, Stephen B. Gruber. Homologous recombination deficiency in lung cancer in the INSPIRE study [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 2047.

Abstract 3599: Proteomic risk factors for prostate cancer: A case-cohort study in EPIC

Abstract Background: Prostate cancer (PCa) is the most prevalent cancer among men in Europe, yet its aetiology is poorly understood. Proteins contribute to the development of carcinogenesis and are also the target of most pharmacological interventions. The examination of associations between plasma proteins and PCa may enhance understanding of the aetiology of the PCa. Aim: Identify proteins associated with PCa risk within a large European prospective cohort, with emphasis on associations with aggressive subtypes of the disease. Methods: We conducted a case-cohort study in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with data for a sub-cohort of 1, 573 individuals and for 982 incident PCa cases. The SomaLogic® 7K panel was used to measure 7, 363 aptamers (representing 6, 412 unique proteins) in plasma samples drawn at recruitment. PCa diagnosis was ascertained by linkage to cancer and death registry data, and was further stratified into aggressive subtypes based on histological grade, tumour stage and mortality information. The Prentice-weight Cox regression model was applied to estimate associations between individual proteins and PCa risk, with adjustment for body mass index, smoking, alcohol intake and education level. Subgroup analyses examined associations with high-grade, advanced-stage, aggressive and extended lag-time (diagnosis more than 15 years after blood draw) PCa risk. We sought external replication for our significant findings in an independent multi-ancestry cohort, the Atherosclerosis Risk in Communities (ARIC) study (SomaLogic® 5K). Results: Following a median follow-up period of 16.2 years, the sub-cohort developed 79 cases of PCa. ACP3, FLT4, and KLK3 [HRs (95% CI): 1.20 (1.10, 1.31), 1.26 (1.13, 1.40) and 2.28 (1.96, 2.65), respectively] were associated with overall PCa risk in EPIC at FDR (false discovery rate) &amp;lt;0.05. In the subgroup analyses, 12 proteins were associated with high-grade, 9 with advanced stage, and 7 with aggressive PCa risk. Among these, ANKRD1 was associated with approximately a 25% higher risk of all three of these clinically relevant subtypes per SD increase. Twelve proteins were associated with PCa risk diagnosed more than 15 years after blood draw, including ANXA2, OSCAR, and SAT2. Two well-established biomarkers of PCa (ACP3 and KLK3) were replicated in ARIC, together with two novel proteins (ANXA2 and APOC2). Conclusion: Multiple novel circulating proteins were associated with PCa risk, particularly with risk for aggressive subtypes. While some proteins may serve as early biomarkers of PCa, those with evidence from long-lag time highlight underlying aetiological mechanisms in the development of PCa. Citation Format: Zhe Huang, Mahboubeh Parsaeian, Vivian Viallon, Ziqiao Wang, Keren Papier, Trishna Desai, Stephanie Chan, Antonio Agudo, Carlotta Sacerdote, David C. Muller, Domenico Pali, Giovanna Masala, Nicholas Wareham, Raul Zamora-Ros, Roel C. Vermeulen, Rosario Tumino, Ian G. Mills, Nilanjan Chatterjee, Elizabeth A. Platz, Pietro Ferrari, Marc Gunter, Elio Riboli, Tim J. Key, Joshua R. Atkins, Karl Smith-Byrne, Ruth C. Travis, The EPIC SomaLogic Working Group. Proteomic risk factors for prostate cancer: A case-cohort study in EPIC [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 3599.

Abstract 4936: The association between plasma IGFBP7 and cancer incidence, cancer mortality, and all-cause mortality in ARIC

Abstract Background: Insulin-like Growth Factor Binding Protein 7 (IGFBP7) may modulate IGF signaling and influence non-IGF molecular mechanisms. We analyzed whether IGFBP7 concentration in plasma is associated with risk of cancer incidence, cancer mortality, and all-cause mortality. Methods: We conducted a prospective cohort analysis of 10, 834 participants (54.8% female, 24.3% Black) with no cancer history for cancer incidence and mortality analyses, and 11, 761 participants (55.6% female, 23.6% Black) for the all-cause mortality analysis in the Atherosclerosis Risk in Communities study. The median follow-up time was 22.8, 23.5, and 25.6 years for the respective analyses. Participants were aged 46-70 years old at start of follow-up. Plasma IGFBP7 was measured using SomaScan® 5K assay, an aptamer-based technology for protein profiling. Incident cancer diagnoses were ascertained by state cancer registry linkage supplemented with medical records and death certificates. Mortality was ascertained by death certificates, including via the National Death Index. We estimated the association between IGFBP7 plasma levels (log2transformed) and outcomes including cancer incidence, cancer mortality, and all-cause mortality using Cox proportional hazards regression models adjusting for age, sex, race, and other potential risk factors for cancer and/or mortality. Results: The association between IGFBP7 and total cancer incidence (3, 347 cases, 200, 279 person-years) was null (HR=0.99, 95% CI 0.85-1.16). However, IGFBP7 was positively associated with lung cancer incidence (479 cases, 199, 823 person-years; HR=1.40, 95% CI 0.93-2.10), unlike for other common cancer sites. The association between IGFBP7 and total cancer mortality (1, 420 deaths, 222, 320 person-years) was statistically significant (HR=1.39, 95% CI 1.10-1.76). Of the common cancers, IGFBP7 was positively associated with lung cancer mortality (HR=1.69, 95% CI 1.10-2.60) and breast cancer mortality (HR=2.09, 95% CI 0.88-4.97). The association between IGFBP7 and all-cause mortality (6, 981 deaths, 262, 734 person-years) was statistically significant and the strongest among the three main analyses (HR=1.72, 95% CI 1.55-1.91). Stratifying by age, the strongest association between IGFBP7 and all-cause mortality was in the youngest age quartile (ages 46.9-52.6 years; HR=2.69, 95% CI 2.01-3.59). IGFBP7 is not strongly correlated with IGF-1 and other family proteins. Conclusions: High circulating IGFBP7 levels may be a risk factor for cancer and all-cause mortality, especially among those in middle adulthood. High circulating IGFBP7 levels may also be a risk factor for both lung cancer incidence and mortality. Additional research and laboratory testing will be necessary to determine whether IGFBP7’s influence on IGF signaling or other mechanisms contribute to tumor progression and mortality, in general. Support: NHLBI, NCI, NPCR Citation Format: Vernon A. Burk, Michael N. Pollak, Corinne E. Joshu, Anna Prizment, Elizabeth A. Platz. The association between plasma IGFBP7 and cancer incidence, cancer mortality, and all-cause mortality in ARIC [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 4936.

Abstract 6183: Social determinants and survivorship care among Black women breast cancer survivors in Maryland

Abstract Purpose: Limited research has examined the impact of social determinants of health (SDOH) on survivorship care experiences exclusively among Black breast cancer (BC) survivors who face survival disparities due their high prevalence of obesity, comorbidities, and inequities in access and quality of care. Survivorship care experiences among Black BC survivors should be examined to identify potential interventions to improve health outcomes. The goal of this study is to test the feasibility of establishing a state-wide cohort study of Black BC survivors residing in Maryland to address this research gap. Methods: This study will recruit 350 Black women BC survivors, aged ≥18 years, and diagnosed with stage I-III primary BC who have completed recommended adjuvant treatment including surgery, chemotherapy, and/or radiation. Recruitment approaches include targeted Facebook ads, outreach to previous study participants, and mailed recruitment letters from the Maryland Cancer Registry (MCR). Participants complete a 30-40-minute online survey, covering demographic and lifestyle factors, clinical and SDOH characteristics, and survivorship care questions. The study also pilots medical record abstractions with the MCR for cancer characteristics and the state designated health-information exchange, Chesapeake Regional Information System for Patients (CRISP), for follow-up care. Results: Recruitment began in July 2024, and by September 2024, 61 self-reported Black participants with a prior diagnosis of BC have completed the survey. The average age at survey is 58.96 (standard deviation (SD)= 11.84)) years, with an average age at diagnosis of 46.42 (SD=13.35) years. 40% are married/living as married, 36.7% are college graduates, all have health insurance, and only 20% reported household incomes &amp;lt;$40, 000/year. Almost half of the survivors self-reported being diagnosed with stage 1 BC (45.9%), followed by 31.1% stage 2, 18% stage 3, and 4.9% unknown stage. The most common self-reported comorbidities include hypertension (39.3%), diabetes (16.7%), and obesity (12.3%). Related to care, 83.3% have a family doctor, and 73.8% received a treatment summary. Additionally, 56.1% and 54.4% consented to medical record linkages with MCR and CRISP, respectively. Recruitment is ongoing. Conclusion: This study will inform future interventions by identifying disparities in survivorship care experiences among Black BC survivors and evaluating the impact of this care on health outcomes. Citation Format: Lensa S. Keno, Camryn Mae Cohen, Kate E. Dibble, Kala Visvanathan, Avonne E. Connor. Social determinants and survivorship care among Black women breast cancer survivors in Maryland [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 6183.

Abstract 2315: Projecting lung cancer incidence in Guam: the impact of smoking prevalence, ethnic disparities, and aging population

Abstract Lung cancer incidence in Guam is slightly lower than in the U.S. overall (50.9 vs. 52.6 per 100, 000), but CHamoru and Micronesian populations have significantly higher rates (69.4 and 78.6 respectively). Given the established link between smoking and lung cancer, this study aims to project lung cancer incidence in Guam considering smoking rates across sex, age, and ethnic groups, accounting for the island's aging population (median age increased from 30.4 in 2010 to 33.7 in 2020). Data on 1, 157 invasive lung cancer cases reported to the Guam Cancer Registry from 2001 to 2020 for individuals aged 34 and older were analyzed. Variables included age, sex, and ethnicity including CHamoru (52.3%), Filipino (20.9%), Micronesian (9.4%), Asian (6.4%), and White (7%). Smoking prevalence data from the 2011-2020 Behavioral Risk Factor Surveillance System (BRFSS) were used to estimate smoking rates for age × sex × ethnicity strata. A Poisson regression model was used to examine relationships between lung cancer incidence rates and demographic factors, including strata-level smoking prevalence. Temporal trends were evaluated across two periods: 2001-2010 and 2011-2020. Predicted rates were applied to 2020 Guam Census population counts to estimate lung cancer cases for 2021-2030 and the annual percent change (APC). From 2011 to 2020, smoking prevalence in Guam declined from 30.2% to 19% (APC = -3.7), with variation among ethnic groups. CHamoru and Asian males had the highest smoking rates. Micronesians showed the largest decrease (APC = -7.3%, from 35% to 10%), while CHamoru males had the smallest reduction (APC = -2.8%, from 46% to 35%). Lung cancer incidence was significantly higher for individuals aged 75+ compared to those aged 35-44 (IRR = 38, 95% CI: 26.9, 55). Males had over twice the rate of females (IRR = 2.3, 95% CI: 2.0, 2.7). Micronesians and CHamorus had significantly higher rates than Filipinos (IRR = 3.5 and 2.4, respectively). Each unit increase in smoking prevalence was associated with a 2% rise in lung cancer incidence for Micronesians and CHamorus. Projected lung cancer cases over 10 years are highest among CHamoru males (246) and females (130). The model predicts annual increases of 1.2% for males and 0.5% for females, with the largest increases among Asian males (2.6%) and Micronesian females (3.3%). Significant differences in lung cancer and smoking rates exist, with the highest burden among CHamorus and Micronesians. Despite a decrease, Guam's 2020 smoking prevalence remained significantly higher than the U.S. average of 12.5%, indicating persistent disparities. This study highlights the need for targeted tobacco control interventions and screening programs to address the evolving cancer burden. This research was funded by the National Cancer Institute Grant: U54CA143728 (University of Guam)/Grant U54CA143727 (University of Hawaii Cancer Center). Citation Format: Cabrini Cruz Aguon, Grazyna Badowski, Aurienne Cruz, Grace G. Bordallo. Projecting lung cancer incidence in Guam: the impact of smoking prevalence, ethnic disparities, and aging population [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 2315.

Abstract 2309: An ecological study on environmental exposure to PFAS and thyroid cancer incidence rates by races/ethnicities in Florida

Abstract Background: The incidence rate of thyroid cancer in the US has increased significantly over the last few decades. However, besides radiation exposure and obesity, no modifiable risk factors have been identified for thyroid cancer. Although theories suggest exposure to per- and polyfluoroalkyl substances (PFAS) could contribute to the development of papillary thyroid cancer, existing studies on the effects of PFAS on thyroid cancer risk do not yield consensus results. Using data for the state of Florida, this ecological study aims to determine whether incidence rates of thyroid cancer vary with respect to residential proximity to industrial facilities handling PFAS materials as well as living in areas where drinking water containing detectable levels of PFAS. Methods: Florida cancer registry data from 2011 to 2020 was used to calculate the incidence rates of papillary thyroid cancer by race/ethnicity (Hispanic, non-Hispanic White (NHW), and non-Hispanic Black (NHB)) for all census tracts in Florida. Environmental Protection Agency data was used to identify the locations of industrial facilities handling PFAS as well as ZIP codes with public drinking water testing positive for PFAS above reportable levels. A geographic information system was used to calculate the number of PFAS facilities within 10KM of a census tract. Correlation, linear regression, and t-tests for sample mean comparison were used to assess the associations between PFAS exposure and thyroid cancer rates at the census tract level. Results: A total of 14,994 cases (9,213 in NHWs, 3,995 in Hispanics, and 989 in NHB) of thyroid cancers were diagnosed in Florida from 2011 to 2020. Correlation analyses show a positive correlation between residential proximity to PFAS facilities and greater Hispanic and NHB population compositions by higher percentages of (r=0.36, p&amp;lt;0.001) with lower income (r=-0.192, p&amp;lt;0.001)) and higher obesity rate (r=0.197, p&amp;lt;0.001)). Regression analyses show that proximity to PFAS facilities is a significant factor for thyroid cancer rates in Hispanic (p=0.006) and NHW (p&amp;lt;0.001). Hispanic and NHW living are in IPZIP code areas with reportable PFAS in drinking water also have higher average thyroid cancer rates than those in areas with no reportable PFAS (t-test p=0.036 for Hispanic and p=0.039 for NHW). With a lower average incidence rate than Hispanic and NHW, thyroid cancer rates in NHB show no statistically significant associations to PFAS exposure. Conclusions: ecological Our findings suggest potential effects of environmental PFAS exposure on thyroid cancer disparities. set up trials to validate these effects by sampling volunteers for blood-level PFAS measurement from neighborhoods with different levels of PFAS exposure (facility proximity and drinking water). Citation Format: Ming S. Lee, Laura Wild, Niko DiStefano, Garrett Forman, Elizabeth Franzmann, Natasha Solle, Alberto Caban-Martinez, Erin Kobetz. An ecological study on environmental exposure to PFAS and thyroid cancer incidence rates by races/ethnicities in Florida [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 2309.

Abstract 4923: The impact of HPV on oropharyngeal cancer tumor microenvironment and survival

The increased incidence of oropharyngeal squamous cell carcinoma (OPSCC) is attributed to increased human papillomavirus (HPV) infections. HPV-positive (HPV+) OPSCC has a better prognosis than HPV-negative (HPV-) OPSCC, highlighting the need to understand the determinants of this difference. The tumor microenvironment (TME) is associated with OPSCC prognosis, but differences due to HPV infection in OPSCC and the impact on survival are not well understood. To address this, de-identified formalin-fixed paraffin-embedded (FFPE) tumor blocks from 191 multiethnic OPSCC patients diagnosed from 1984-2004 were collected from three population-based cancer registries in the Surveillance, Epidemiology, and End Results Residual Tissue Repositories (Los Angeles, Hawai’i, and Iowa). HPV16 status was extracted from an earlier study (Chaturvedi et al, 2011) using in-situ hybridization (ISH) and line probe assays (LiPA), and HPV- tumors were further confirmed using p16 INK4a immunohistochemistry (IHC). Specimens that were ISH/LiPA negative and p16 positive were excluded (n=24). Sections were stained for CD3, CD8, CD163, B2M (HLA-I), and HLA-DP/DQ (HLA-II), using IHC. Counts of positive cells (CD3+, CD8+, and CD163+) were quantified using Visiopharm digital image analysis, while HLA stains were manually scored in tumor cells and used to identify dendritic cells (DC). Analysis of HPV16 tumor status and TME biomarker positive counts were compared using the nonparametric Mann-Whitney U test, and associations between the TME biomarkers and overall survival (OS) were analyzed using multivariable Cox regression to estimate the hazard ratio (HR) of TME biomarkers adjusted for age at diagnosis, sex, race/ethnicity, and SEER stage. There were 53 HPV+ and 114 HPV- patients included in the study after exclusions. Patients were primarily non-Hispanic white (56%) and male (80%); median age at diagnosis was 60. There were significantly higher levels of CD3+ (p&amp;lt;0.0001) and CD8+ (p&amp;lt;0.0001) T-cells in HPV+ compared to HPV- OPSCCs, and HPV+ tumors had reduced HLA-I expression (p&amp;lt;0.0001). High CD8+ T-cell levels were associated with better OS in HPV+ OPSCC (HR=0.21, p=0.036) but worse OS in HPV- OPSCC (HR=2.4, p=0.035). In HPV- tumors, HLA-II expression was associated with worse survival (HR=2.4, p=0.034), but HLA-II expression on DC in HPV+ tumors was strongly associated with improved survival (HR=0.07, P=0.025). In a subgroup (n=75; 36 HPV+, 39 HPV-), CD3+ and CD8+ T-cell infiltrations were higher in both tumoral (p&amp;lt;0.007; p&amp;lt;0.0001, respectively) and stromal areas (p=0.002; p&amp;lt;0.0001, respectively) of HPV+ compared to HPV- tumors. Higher stromal CD163+ macrophage infiltration was associated with worse OS in HPV+ tumors (HR= 4.3, p=0.030). These findings provide evidence that HPV+ OPSCC tumors have distinct TME profiles and associations with OS compared to HPV- OPSCC tumors and that the immune cell location within the TME is also important. Citation Format: Esther Lam, Jia Y. Wan, Rachel Bolanos, Brenda Y. Hernandez, Charles F. Lynch, Robert A. Edwards, Anil K. Chaturvedi, Adrian J. Correa, Arjan Diepstra, Wendy Cozen. The impact of HPV on oropharyngeal cancer tumor microenvironment and survival [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 4923.

Abstract 4929: Differences in cancer risk by environmental disparities in Puerto Rico: findings from 2016-2020 cancer data

Abstract Background: Chemical contaminants have been established as risk factors for certain types of cancer including breast and prostate, which are the most commonly diagnosed cancers in Puerto Rico among women and men, respectively. By law, industries report their chemical emissions to air, water, and soil to the Environmental Protection Agency’s Toxic Release Inventory Sites (TRI) program. In 2006, Puerto Rico had 148 TRI facilities across 49 of the 78 municipalities, releasing 518 chemicals, including 170 carcinogens such as arsenic, benzene, radon, and trichloroethylene. This ecological study assesses the strength of the association between cancer risk and municipalities with environmental disparities (contaminated vs. non-contaminated sites) in Puerto Rico. Methods: Cancer incidence data from 2016 to 2020 were obtained from the Puerto Rico Central Cancer Registry. Contaminated sites, defined as municipalities with TRI facilities, were identified using data from the TRI program in 2006 (10 years before the estimation of cancer risk). To estimate cancer risk between contaminated and non-contaminated sites, we calculated the standardized incidence relative risk (RR = standardized rate of contaminated sites / standardized rate of non-contaminated sites) with 95% confidence intervals (95% CI) from 2016 to 2020 by type of cancer and sex. All analyses were conducted using SEER*Stat v8.4.4. Results: Between 2016 and 2020, 71,814 new cancer cases were diagnosed in Puerto Rico, 37,582 among males and 34,232 among females. The RR for residents of contaminated sites showed a significant excess risk of 7% (95%CI: 1.05-1.09, p&amp;lt;0.0001) for all types of cancer compared to residents of non-contaminated sites; similar findings were observed in both men (9%, CI 1.06-1.12, p&amp;lt;0.0001) and women (6%, CI 1.03 -1.09). When evaluating the risk of female-related cancers, excesses of 6% (95%CI: 1.01-1.11, p=0.01) and 24% (95%CI: 1.04-1.49, p=0.02) were observed for breast and ovarian cancers, respectively, among residents of contaminated sites compared to residents of non-contaminated sites. For male-related cancers, an excess risk of 10% (95%CI: 1.06-1.14, p&amp;lt;0.0001) was observed for prostate cancer among residents of contaminated sites compared to residents of non-contaminated sites. Conclusions: Our findings suggest a significant excess in cancer incidence among residents in municipalities with TRI facilities overall and for certain cancer types. These results underscore the need for targeted environmental interventions and public health actions to mitigate exposure to carcinogens in Puerto Rico. Acknowledgments: This study was supported by the Caribbean Climate Change Adaptation, Cancer, and Health Disparities Research Center (CARIB-CARES) funded by the National Cancer Institute (NCI, award # 1P20CA294096-01). Citation Format: Nancy Raquel Cardona, Ana P. Ortiz, Carlos R. Torres, Polaris Torres-Rodríguez, Karen Ortiz-Ortiz, Noreen Michael, Pablo Mendez-Lazaro, Marievelisse Soto-Salgado. Differences in cancer risk by environmental disparities in Puerto Rico: findings from 2016-2020 cancer data [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 4929.

Abstract 3581: Psychosocial factors associated with lung cancer incidence and survival among individuals with low income in the Southeastern U.S.

Background: Lung cancer is the leading cause of cancer-related mortality in the U.S. and significant racial inequities exist. Psychosocial factors, including stressful life experiences, have been linked to increased incidence and poorer outcomes. The purpose of this study was to identify psychosocial factors associated with lung cancer incidence and survival among a low-income, racially diverse population in the U.S. South. Methods: We utilized data from the Southern Community Cohort Study (SCCS), a large, prospective study across 12 Southeastern states, enrolling participants from 2002-2009, to examine psychosocial factors and lung cancer incidence and survival. Incident cancers and deaths were identified by linkage with state cancer registries and the National Death Index, respectively. Individual-level social, behavioral, and medical history information was ascertained at baseline via questionnaire. We examined depression, spirituality, attendance at faith-based services, social support, and use of anti-depressant/anxiety medication. We also analyzed data from a subset of participants who responded to psychosocial questions collected on a follow-up survey. We used Cox regression analyses to identify factors associated with lung cancer incidence and survival overall and by race. Results: Among 74,295 SCCS participants, approximately 69.8% self-reported as Black persons, 58.4% female, and 56.3% had an annual household income below $15,000. There were 1,569 incident lung cancer cases identified, of whom, almost half (49.2%) were diagnosed at distant stage. Overall, lower spirituality was associated with a reduced risk of lung cancer. Among Black participants, identifying as “fairly” vs. “very” spiritual was associated with a 15% lower risk (HR: 0.85; 95% CI: 0.74-0.97); a similar pattern was observed among White participants but was not statistically significant. Similar patterns were observed with mortality. In subset analyses among 367 participants with lung cancer, depression and less frequent attendance at faith-based services were associated with greater mortality. Among Black participants, those with depression had 2.75-fold greater mortality (95% CI:1.11-6.84) compared to those without depression, and those who attended faith-based services at least once per week had 50% lower mortality compared to those who attended less than once per week (HR: 0.50; 95% CI: 0.30-0.83). Among White participants, identifying as “slightly/not at all” vs. “very” spiritual was associated with 4.31-fold greater mortality (95% CI: 1.47-12.66). Conclusions: Psychosocial factors and spirituality may play a role in inequities observed in lung cancer outcomes. Future research should investigate how psychosocial factors may impact lung cancer outcomes. Citation Format: Anna Junkins, Jennifer Richmond, Douglas DeMoulin, Xijing Han, Heather Munro, Martha J. Shrubsole, Wei Zheng, Xiao Ou Shu, Melinda C. Aldrich. Psychosocial factors associated with lung cancer incidence and survival among individuals with low income in the Southeastern U.S [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 3581.

Abstract 3592: Hospital-treated infectious diseases and pancreatic cancer risk: Findings from a large population-based cohort

Abstract Rationale: Inflammation has been established as a mechanism for pancreatic cancer development. The longitudinal relationship between infection, and the resulting inflammation, and pancreatic cancer risk has yet to be elucidated. A large population-based cohort, such as the United Kingdom (UK) Biobank, offers a unique opportunity to assess these relationships with long follow-up time and a large number of infections. Objectives: Estimate the effect of hospital-treated infection on pancreatic cancer risk by infection type and infection burden. Methods: UK Biobank participants with no record of pancreatic cancer at cohort entry were included. Follow-up was to February 29, 2020 and January 31, 2021 for participants from England and Wales, and Scotland, respectively. Hospital-treated infection status was obtained through linkage to hospital inpatient data and allowed for characterization of exposure to over 900 infectious diseases using the International Classification of Diseases and Related Health Problems 10th Revision. Incident pancreatic cancer diagnosis was obtained through linkage to national cancer registries. Relative risk (RR) and associated 95% confidence intervals (CI) were estimated for infectious disease groups and infectious disease burden categories using negative binomial regression models. Results: From cohort entry to the end of follow up, 502, 219 people were included in the cohort. 93, 123 participants had at least one recorded exposure to hospital-treated infection preceding pancreatic cancer diagnosis and 1, 255 were diagnosed with pancreatic cancer throughout the follow up period. Exposure to any hospital-treated infection was associated with increased risk of pancreatic cancer (aRR 2.56 [95% CI 2.27, 2.88]). When considering infection burden, a dose-response relationship was seen (ptrend &amp;lt; 0.001) where a greater number of infections was associated with a greater risk of pancreatic cancer. When compared to those with no infection, participants had increasing risk with 1 infection (aRR 1.99 [95% CI 1.69, 2.35]), 2 infections (aRR 2.84 [95% CI 2.34, 3.43]), and &amp;gt;3 infections (aRR 3.21 [95% CI 2.72, 3.78]). Conclusions: Infections which require treatment in hospital are associated with risk of pancreatic cancer. This association was strongest when considering bacterial infection and its impact on longitudinal risk of pancreatic cancer. Further, the dose-response relationship observed when investigating infection burden may suggest a cumulative risk of pancreatic cancer conferred with severe infections. Citation Format: Kiera R. Murison, Rayjean J. Hung. Hospital-treated infectious diseases and pancreatic cancer risk: Findings from a large population-based cohort [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 3592.

Abstract 2280: Whole-exome sequencing analysis of early-onset soft tissue sarcoma in a multiethnic family-based population study

Abstract Background: Sarcomas are a rare group of cancers originating in bones and soft tissues, and represent approximately 1% of adult cancers and 15-20% of pediatric cancers. The development of sarcomas is often driven by inherited or de novo mutations in genes involved in critical processes such as cell growth, development, and signaling pathways, which play central roles in their pathogenesis. Notably, the risk of early-onset cancer (diagnosed before the age of 29) is significantly elevated—68 times higher—in siblings of individuals with soft tissue sarcomas, suggesting a strong contribution of inherited germline variants to the observed familial cancer risk. Methods: Cancer patients included in this study were identified using a linked dataset integrating information from the California Cancer Registry and the California Birth Statistical Master File. To explore rare genetic predispositions associated with soft tissue sarcomas, a cohort of 54 patients from 43 families was analyzed. This cohort included 11 sibling pairs, each with at least one individual diagnosed with soft tissue sarcoma, ICDO-3 histology code 8900-8991. Additionally, 32 unrelated individuals diagnosed with multiple cancers, including soft tissue sarcoma, were included in the analysis. Whole-exome sequencing (WES) was performed on neonatal dried blood samples from these 54 participants. Germline short variant discovery, including single nucleotide variants and insertions/deletions (indels), was conducted using the Genome Analysis Toolkit pipeline. Variants were annotated according to guidelines from the American College of Medical Genetics and Genomics. Results: A total of 603 cancer-associated variants were identified in this study, with 74 variants detected in multiple individuals. Among these, 12 variants were classified as “Pathogenic/Likely Pathogenic, ” two of which were found in two children each. Notably, a mutation in the NF1 gene, previously linked to Neurofibromatosis Type 1 syndrome, was confirmed in a Latino-White family, where one child presented with mixed-type rhabdomyosarcoma and another with neurofibroma. Additionally, a novel association was observed between the USP6 gene mutation and rhabdomyosarcoma diagnosis in two unrelated Southeast Asian individuals, one of Filipino descent and the other Guamanian. Furthermore, a homozygous mutation in the AR gene on the X chromosome was identified in a single patient. Conclusion: Our study employs WES analysis to investigate predisposition genes in individuals diagnosed with soft tissue sarcoma, alongside their cancer-affected siblings. Through this analysis, we have identified novel genetic mutations linked to soft tissue sarcoma diagnosis. Additionally, certain variants appear to exhibit ancestry-specific patterns in this multiethnic population. Citation Format: Naying Zhou, Joseph L. Wiemels. Whole-exome sequencing analysis of early-onset soft tissue sarcoma in a multiethnic family-based population study [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 2280.

Abstract 3601: Elevated short-chain fatty acid level and increased risk of hepatocellular carcinoma in a prospective cohort study

Background: Hepatocellular carcinoma (HCC) makes up 80-90% of primary liver cancers and is typically detected at an advanced stage because of its silent nature of progression and a lack of effective non-invasive early detection biomarkers. Gut-derived metabolites such as short-chain fatty acids (SCFAs) play a key role in liver health and may impact the progression of early non-malignant stages of liver disease to malignant transformation to HCC. Although most of studies have shown that SCFAs including acetate, butyrate, and propionate have been associated with lower risk of intestinal disease, some experimental studies have shown dysregulated metabolism of SCFAs may induce proinflammatory milieu for liver disease progress. The goal of this study is to investigate whether metabolomic profiling of SCFAs in baseline serum is associated with risk of HCC development. Methods: We performed a nested case-control study with 100 incident HCC cases and 100 individually matched healthy controls within the Singapore Chinese Health Study, a cohort of 63,257 men and women aged 45-74 years at enrollment in 1993-1998. The incidence of HCC among cohort participants was annually surveilled using the nationwide Singapore Cancer Registry. Serum acetic, butyric, propionic, and valeric acids were quantified using ultra-performance liquid chromatography triple-quadrupole mass spectrometry assays. The conditional logistic regression was used to evaluate the association between SCFAs and HCC risk using odds ratios (ORs) and their 95% confidence intervals (CI). Results: Cases and controls were comparable in distributions by age, body mass index (BMI), alcohol consumption and smoking status. Individuals with HCC were more likely to be HBsAg positive and had a history of diabetes than controls. Among controls, the summed all SCFAs and total butyric acid and its metabolites were positively associated with BMI (P trend &amp;lt; 0.05). The summed and most of individual SCFAs measured were significantly elevated in HCC compared with controls. Compared to the lowest tertile, the OR (95% CI) of HCC for the highest tertile of summed all SCFAs and total butyric acids was 3.24 (1.45-7.24) and 2.78 (1.27-6.12) after adjusting for age, sex, BMI, alcohol consumption, smoking status, type 2 diabetes, and HBsAg status (both P’s for trend &amp;lt; 0.01). Conclusion: The present analysis demonstrated a statistically significant association between elevated SCFA levels and increased risk of HCC in a prospective cohort of Singaporean Chinese. These results align with increased risk of HCC within this cohort with elevations in other metabolites such as bile acids. Mapping metabolic profile changes in liver disease progression to cancer will provide clinicians with a novel biomarker for risk stratification and early detection. Citation Format: Sindhu Karnam, Wei Jia, Renwei Wang, Jennifer Adams-Haduch, Woon-Puay Koh, Jian-Min Yuan. Elevated short-chain fatty acid level and increased risk of hepatocellular carcinoma in a prospective cohort study [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 3601.

Abstract 4949: Late-stage breast cancer risk and five-year survival by stage at diagnosis among top 5 Asian ethnic subgroups in California

Abstract Introduction: Breast cancer (BC) incidence over the past decade has been rapidly increasing among Asian American (AA) women compared to non-Hispanic White (NHW) women. AA women are more likely to be diagnosed with BC at an earlier stage and have better survival compared to Hispanic and Black women. However, the aggregation of AA may conceal significant population heterogeneity and health disparities among ethnic subgroups, as the risk profile in one subgroup differ from another. Thus, we aimed to understand AA ethnic disparities in BC by assessing AA subgroups and their relationship with late-stage diagnosis and all-cause mortality by stage at diagnosis using a cohort of AA BC patients from the California Cancer Registry (CCR). Methods: We identified BC cases among NHW and among the top 5 AA subgroups (Chinese, Japanese, Filipino, Korean, and Vietnamese) diagnosed in California between 1988 to 2020 using the CCR. We conducted multivariable logistic regression to evaluate the association between the odds of being diagnosed with late-stage BC (regional and distant stages) and AA subgroups. Additionally, 5-year observed survival rates across each AA subgroup were calculated at each stage at diagnosis (in situ or localized, regional, and distant). Lastly, we conducted multivariable Cox proportional hazards regression to assess all-cause mortality by AA subgroups. All models were adjusted for year at diagnosis, age at diagnosis, nativity, socioeconomic status (SES), comorbidity, insurance status, and BC subtype. We used NHW as the reference group. Results: Our sample contained a total of 557,551 BC cases (NHW N=493,227; Chinese N=19,380; Japanese N=8,893; Filipino N=24,938; Korean N=5,075; Vietnamese N=6,038). We found that Chinese, Japanese, Korean, and Vietnamese women were less likely to be diagnosed with late-stage BC compared to NHW (p&amp;lt;0.01 for Chinese, Japanese, and Vietnamese; p=0.02 for Korean), while no difference was observed for Filipino women (p=0.72). When comparing the 5-year observed survival rates from all causes of death by stage at diagnosis, all 5 AA subgroups had higher 5-year survival compared to NHW across all stages. However, when adjusted for year at diagnosis, age at diagnosis, nativity, SES, comorbidity, insurance status, and BC subtype, Chinese women diagnosed at the distant stage were 25% more likely than NHW women to die from all causes (p&amp;lt;0.01). Conclusions: Most AA subgroups were at lower odds of being diagnosed with late-stage BC compared to NHW, except for Filipino women. Survival outcomes also differed by subgroups and by stage at diagnosis. Differences in AA subgroups could be due to several factors (i.e., social factors, environmental factors). Thus, different cancer strategies in terms of cancer control and care improvement for each group are needed. Citation Format: Michelle Tran, Kimberly A. Miller, Sue E. Kim, Kali Zhou, Myles Cockburn, Lihua Liu. Late-stage breast cancer risk and five-year survival by stage at diagnosis among top 5 Asian ethnic subgroups in California [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 4949.

Abstract 6228: Spatial regression analysis for colorectal cancer mortality rates in Puerto Rico: 2012-2016 and 2017-2021

Abstract Objective: Despite efforts to improve screening and early detection, colorectal cancer (CRC) remains a leading cause of cancer-related deaths in Puerto Rico. This study aimed to analyze the spatial distribution of CRC mortality rates (MR) in Puerto Rico during two time periods—2012-2016 (before Hurricane Maria) and 2017-2021 (after Hurricane Maria, earthquakes, and the onset of the COVID-19 pandemic) to identify factors contributing to the observed mortality rates. Methods: Age-adjusted CRC MR for 2012-2016 and 2017-2021 were obtained from the Puerto Rico Central Cancer Registry (PRCCR). Sociodemographic data were sourced from the American Community Survey using the tidycensus R package. The study included 34 treatment centers across Puerto Rico and employed Spatial Cross-Regressive Models (SLX) to examine the influence of factors such as distance to treatment centers, median income, transportation access, and age distribution on CRC MR. Statistical analyses were conducted using R version 4.4.1 (R Foundation for Statistical Computing) and R-Studio (Posit Software, PBC). Results: In simple models, distance to treatment centers significantly impacted CRC mortality in both periods but with reduced influence in 2017-2021 (2012-2016: coefficient = -0.5, p &amp;lt; 0.01; lag coefficient = -37.6, p &amp;lt; 0.01 vs. 2017-2021: coefficient = -0.37, p &amp;lt; 0.05; lag coefficient = -28.9, p &amp;lt; 0.05). In multivariate models, additional sociodemographic factors were significant in 2012-2016, including: Proportion of workers without vehicles (coefficient = 3.22×102, p &amp;lt; 0.01; lag coefficient = 2.55×104, p &amp;lt; 0.01), Median income (coefficient = 7.03×10-3, p &amp;lt; 0.01; lag coefficient = 5.24×10-1, p &amp;lt; 0.01), and Proportion of inhabitants aged 18 or younger (coefficient = 5.6×102, p &amp;lt; 0.01; lag coefficient = 3.95×104, p &amp;lt; 0.01). However, in 2017-2021, these variables were no longer significant, suggesting the impact of systemic disruptions from disasters and the pandemic. Conclusions: The findings indicate that CRC mortality in Puerto Rico is driven more by sociodemographic factors such as income and transportation access than by geographic proximity to treatment centers. The reduced significance of these factors in 2017-2021 emphasizes the need for further studies to understand the compounded effects of natural disasters and the COVID-19 pandemic. Addressing disparities in transportation, income, and healthcare accessibility is essential to reducing CRC mortality in Puerto Rico. Citation Format: Brenda C. Torres-Velásquez, Liliana M. Castro-Jiménez, Carlos R. Torres-Cintrón, Elba V. Caraballo. Spatial regression analysis for colorectal cancer mortality rates in Puerto Rico: 2012-2016 and 2017-2021 [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 6228.

Abstract 2336: Discovering plasma proteins associated with common solid cancer incidence in ARIC

Background: Plasma proteins, reflecting both exogenous and endogenous factors, could serve as the basis for risk stratification to guide decision-making for primary and secondary prevention of cancer in adults. Published studies have investigated the prospective risk of cancers and other chronic diseases associated with Olink-based proteomic data available in the UK Biobank Study. There is a need for further investigations based on alternative measurement platforms, longer follow-up data, and diverse populations. Aim: Identify proteins measured by SomaScan assay® 5K that are associated with risk of solid cancers in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort of middle-aged and older Black and White men and women. Methods: The study was conducted based on a cohort of 9,495 individuals for which a total of 590, 416, 22, 97, 271, 88, 136 incident cancers of prostate, lung, liver, kidney, colorectal, pancreatic, and bladder were observed over a maximum follow-up period of 25.9 years. Log2-transformed relative fluorescence unit of 4,955 SOMAmers measured in plasma collected at Visit 2 were adjusted in a linear regression model including proteomic PEER factors, study sites, and ten genetic principal components (PCs). Corrected protein quantifications based on rank-inverse normalization of the residuals were used in the analysis. Incident cancers were ascertained primarily by cancer registry linkage. The Cox regression model and time-dependent coefficient Cox model for age at Visit 2 were applied to estimate associations between individual proteins and each solid cancer risk, adjusting for potential environmental risk factors, race, genetic PCs, and PEER factors. Sensitivity analyses examined associations with extended lag-time (diagnosis more than 5 years after Visit 2) and minimally adjusted Cox model for cancer risk. Results: We identified 32 proteins (19 positively, 13 inversely) for liver cancer risk, 5 proteins (4 positively, 1 inversely) for lung cancer risk in both main and sensitivity analyses at false discovery rate (FDR) &amp;lt;0.05. 2 known proteins (MMP7 and HAVCR1) were identified to be positively associated with kidney cancer, and 2 (ACP3 and KLK3) were identified for prostate cancer. We further identified GSTM1 associated with bladder cancer risk [HR (95% CI): 0.68 (0.56, 0.82)] and found evidence of enrichment of signals for proteomics association with colorectal cancer at nominal threshold P &amp;lt; 0.05 (371 proteins for colorectal cancer, 401 proteins for colon cancer only, and 425 proteins for rectal cancer). Conclusion: We discovered multiple circulating proteins associated with lung and liver cancer risks, and confirmed previously established circulating proteins for kidney and prostate cancer risks. Additional evaluations in independent and large cohort studies and laboratory testing will be necessary to validate our results. Support: NHGRI, NHLBI, NCI, NPCR. Citation Format: Ziqiao Wang, Vernon A. Burk, Nilanjan Chatterjee, Elizabeth Platz. Discovering plasma proteins associated with common solid cancer incidence in ARIC [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 2336.