bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 839: Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer
Authors: Tadesse Deborah , Rothman Nathaniel , Xie Shuai , Hurwitz Lauren , Friesen Melissa C. , Baris Dalsu , Schwenn Molly , Johnson Alison , Karagas Margaret , Silverman Debra T. , Koutros Stella 
Published: March 2024

Abstract
Introduction: Recent studies have reported an increased bladder cancer risk with occupational exposure to organic solvents, including exposure to benzene, toluene, and xylene (BTX). The metabolism of solvents is known to be influenced by genetic susceptibility. Here, we evaluated the association between BTX and bladder cancer, stratified by genotype in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of solvents.
Methods: We evaluated if single-nucleotide polymorphisms (SNPs) modified the association between BTX exposure and bladder cancer risk in 1182 cases and 1408 controls from a population-based case-control study in New England. Ever and cumulative lifetime exposure to BTX was assessed using occupational histories obtained by personal interviews and exposure-oriented modules in conjunction with a job-exposure matrix. Genotyping was conducted using Illumina arrays and GSTM1 and GSTT1 deletion were determined using melt curve/copy number assays. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between BTX exposure and bladder cancer, stratified by genotype and to calculate p-values for multiplicative interaction.
Results: Ever exposure to BTX was more strongly associated with bladder cancer risk among individuals with the GSTT1 null (deletion) genotype (OR 3.53, 95% CI 1.26-9.89), while exposed individuals with the GSTT1 active genotype had a diminished risk (OR 1.40, 95% CI 0.93-2.10, P-interaction = 0.06). The association between benzene exposure and bladder cancer was similarly modified by GSTT1 genotype (carriers of the deletion: OR 5.19, 95% CI 1.91, 14.13; carriers of one or two copies: OR 1.22, 95% CI 0.79, 1.89, p-interaction=0.008).
Conclusion: GSTT1 genotype has been shown to impair the metabolism of solvents, particularly for benzene. Here we show that bladder cancer risk is higher among those exposed to solvents who also harbor a common deletion in GSTT1, adding to the evidence of a plausible link between BTX exposures and bladder cancer risk.
Citation Format: Deborah Tadesse, Nathaniel Rothman, Shuai Xie, Lauren Hurwitz, Melissa C. Friesen, Dalsu Baris, Molly Schwenn, Alison Johnson, Margaret Karagas, Debra T. Silverman, Stella Koutros. Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 839.
Abstract 840: Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma
Authors: Rhee Jongeun , Koponen Jani , Sampson Joshua N. , Keil Alexander P. , Ward Mary H. , Hofmann Jonathan N. , Huang Wen-Yi , Silverman Debra T. , Rantakokko Panu , Purdue Mark P. 
Published: March 2024

Abstract
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants, some immunotoxic, that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and non-Hodgkin lymphoma (NHL); however, it is unknown whether associations exist at lower exposure levels that are more common in the general population. To address this knowledge gap, we conducted a nested case-control study investigating serum PFAS concentrations and NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations (collected between 1993-2001) of five PFAS among 706 cases and 706 controls individually matched on the basis of age at baseline, sex, self-reported race and ethnicity, study center, calendar year of blood collection, and number of prior serum thaws. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PFAS concentrations in relation to NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with NHL for any of the five PFAS in analyses adjusting for all measured PFAS. In analyses of histologic subtypes, we observed a positive association between perfluorohexane sulfonate (PFHxS) and DLBCL (OR per doubling in concentration=1.27, 95% CI=1.07, 1.50) which remained for cases diagnosed ≥10 years after blood collection (OR=1.34, 95% CI=1.09, 1.64). We also observed inverse associations with PFNA for all subtypes (DLBCL, OR=0.84, 95% CI=0.72, 0.98; FL, OR=0.86, 95% CI=0.69, 1.08; LPL/MZL, OR=0.86, 95% CI=0.66, 1.12), although these associations were null among participants with blood drawn prior to 1997 (DLBCL: OR&lt;1997=0.95, OR≥1997=0.67, Pinteraction=0.001; FL: OR&lt;1997=1.01, OR≥1997=0.77, Pinteraction =0.08; LPL/MZL: OR&lt;1997=1.26, OR≥1997=0.88, Pinteraction =0.03). In conclusion, our findings from a cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation.
Citation Format: Jongeun Rhee, Jani Koponen, Joshua N. Sampson, Alexander P. Keil, Mary H. Ward, Jonathan N. Hofmann, Wen-Yi Huang, Debra T. Silverman, Panu Rantakokko, Mark P. Purdue. Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 840.
Abstract 853: Assessment of racial and ethnic disparities in environmental exposure-related cancer burden
Authors: Bobbitt Jessica R. , Liu Fangzhou , Cullen Jennifer , Keri Ruth A. 
Published: March 2024

Abstract
The United States Environmental Protection Agency designates superfund sites as regions contaminated with hazardous waste. These sites have previously been associated with adverse health outcomes, including an increased incidence of cancer. Historically, communities with racial and ethnic minorities and people of low socioeconomic status have served as prime locations for these sites, as these communities have lacked the ability to advocate against this land use. Here, we ask whether racial and ethnic minorities are disproportionately exposed to these sites or other regions of hazardous waste in our catchment area at the Case Comprehensive Cancer Center, and in the state of Ohio. Further, we are examining whether areas of high exposure are associated with adverse health outcomes including higher cancer incidence and mortality. We utilized the Environmental Justice Index (EJI) database from the Centers for Disease Control and Prevention to assess, on a census tract level, the percent of racial and ethnic minorities in a region, defined as all persons except white, non-Hispanic individuals. We also queried hazardous and toxic waste sites including regions with a national priority list site, a toxic release inventory site, treatment, storage, and disposal sites, risk management plan sites, coal mines, and lead mines. We intersected these data and found that census tracts with a higher percentage of minority persons were more likely to be exposed to hazardous and toxic sites. Our current studies are assessing whether this high environmental burden is contributing to disproportionately worse cancer burden for these individuals. We will test this by comparing EJI data with data from the Ohio Cancer Incidence Surveillance System database to assess cancer incidence and mortality in Ohio. This will also provide an avenue for identifying specific exposures that may contribute to different cancer types. Further, we plan to assess if persons with low socioeconomic status or those living with disabilities are disproportionately affected by environmental burden. Overall, understanding environmental burden and health outcomes will facilitate the prioritization of communities at greatest need, contributing to greater health equity.
Citation Format: Jessica R. Bobbitt, Fangzhou Liu, Jennifer Cullen, Ruth A. Keri. Assessment of racial and ethnic disparities in environmental exposure-related cancer burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 853.
Abstract 888: Uncovering clinically relevant omics signatures from pan-cancer imaging and multi-omics data integration
Authors: Wang Joshua , Hong Runyu , Tan Jimin , Liu Wenke , Fenyȯ David 
Published: March 2024

Abstract
Despite advancements in deep learning for histopathology, integrating these insights with multi-omics data to uncover clinically relevant omics pathway-level signatures remains a challenge. Our study addresses this gap by applying unsupervised learning techniques on pan-cancer multi-omics data, leveraging 3,080 Hematoxylin and Eosin (H&E) images from 1,010 patients in Clinical Proteomic Tumor Analysis Consortium (CPTAC) to uncover omics pathway-level signatures that drive discernable morphology phenotypes at the tissue level. First, imaging models were trained to predict clinical and mutation outcomes, and thereafter, integrated with transcriptomic and proteomic expression data using sparse canonical correlation analysis. Our findings reveal that images of TP53 mutated samples exhibited increased nuclear size and dense lymphoplasmacytic infiltration. These morphological changes correlated with neutrophil and macrophage signaling at the proteomic level, and IL-1 mediated signaling at the transcriptomic level, highlighting the complementary perspectives different omics can provide.
To further elucidate immune interactions, we applied multi-omics deconvolution to identify 7 immune subtypes, characterizing each with gene set enrichment, germline DNA variations, and kinase activations. We show that imaging models trained to predict these subtypes differentiate tissue morphologies corresponding to immune enrichment (AUROC: 0.84). To further confirm the robustness of our approach, we trained models to predict co-regulated proteomic modules clustered by independent component analysis. We demonstrate a signature in pan-squamous tumors, consisting of T cell markers and interferon-gamma response proteins like CD4, CD48, and GBP5, which imaging models can successfully predict from histopathology. Manual review from pathologists confirmed lymphocytic T-cell density as a differentiator in samples with the highest and lowest T-cell signaling.
Together, these approaches demonstrate that genomic characteristics discovered via unbiased mining of pan-cancer multi-omics data manifest as quantitative imaging phenotypes. These results underscore the potential of multi-omics and digital pathology to integratively uncover and confirm new cancer biology. Our ongoing work will explore predicting drug response and survival from morphology patterns related to multi-omics signatures.
Citation Format: Joshua Wang, Runyu Hong, Jimin Tan, Wenke Liu, David Fenyȯ. Uncovering clinically relevant omics signatures from pan-cancer imaging and multi-omics data integration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 888.
Abstract 946: Landscape of HRD aberration in EGFR mutated lung cancer and the role of PARP-inhibitor in EGFR mutated lung cancer with HRD aberration
Authors: Kim Jinah , Choi Horyun , Chung Liam Il-Young , Chae Young Kwang 
Published: March 2024

Abstract
Introduction: Olaparib, an oral poly polymerase (PARP) inhibitor has received approval for treating malignancies displaying homologous recombination deficiency (HRD). Current data is insufficient in establishing the role of PARP inhibitors in non-small cell lung cancer (NSCLC) in the setting of third generation EGFR tyrosine kinase inhibitor (TKI) use. Preclinical investigation suggests heightened PARP inhibitor sensitivity of TKI-resistant EGFR mutant NSCLC cells compared to TKI-sensitive cells.
Methods: We utilized The Cancer Genome Atlas (TCGA) to investigate the prevalence of HRD gene mutations in patients with NSCLC harboring EGFR mutations. We also present a case demonstrating a favorable response to the dual therapy of olaparib and osimertinib in NSCLC harboring EGFR, RAD50, and ARID1A mutations that progressed on osimertinib.
Results: There were 2298 patients in the NSCLC cohort (MSKCC database). Among 687 patients with EGFR mutations, 24 patients (3.5%) exhibited ARID1A mutations, 8 patients (1.2%) had BRCA1 mutations, 11 patients (1.6%) had BRCA2 mutations, and 5 (0.7%) had RAD50 mutations. A 71-year-old female presented with stage IV adenocarcinoma of the lung. She had recurrent malignant pericardial effusion requiring pericardiocentesis for previous cardiac tamponade. Computed tomography (CT) of the chest revealed a 3cm irregular left hilar mass with bilateral mediastinal and hilar lymph nodes. Tissue next generation sequencing (NGS) at baseline identified EGFR exon19 deletion along with RAD50 R726H which is a HRD pathway gene. Circulating tumor DNA (ct-DNA) NGS (Guardant360) showed EGFR E746_A750del 4.8%. The patient achieved partial response to osimertinib for 28 months. Follow-up CT showed disease progression. Olaparib 200mg twice daily was added to osimertinib based on repeat ct-DNA NGS indicating a new ARID1A alteration (splice site SNV) along with the known BRCA1 mutation. Follow up scans currently have consistently demonstrated ongoing partial response for 19 months. Combining olaparib with osimertinib can be effective in an osimertinib-resistant NSCLC patient with EGFR mutation and HRD aberration. The favorable response could be attributed not only to pre-existing RAD50 mutation but also to acquired mutations in ARID1A HRD genes.
Conclusion: HRD aberrations are uncommon in EGFR mutated lung cancer patients. Further investigation on the role of PARP inhibitor in EGFR mutated lung cancer is warranted.
Citation Format: Jinah Kim, Horyun Choi, Liam Il-Young Chung, Young Kwang Chae. Landscape of HRD aberration in EGFR mutated lung cancer and the role of PARP-inhibitor in EGFR mutated lung cancer with HRD aberration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 946.
Abstract 997: Bringing the first prehabilitation program to American Indian cancer patients
Authors: Erdrich Jennifer , Hernandez Adriena , Bea Jennifer W. , Thomson Cynthia A. 
Published: March 2024

Abstract
Purpose. American Indian/Alaska Native (AI/AN) people have the worst cancer survival rates of any US racial group, are underrepresented in clinical trials and research, and have never been recruited for participation in any published prehabilitation (prehab) intervention conducted prior to cancer surgery.
Description of Procedure. We are collaborating with tribal partners to design the first prehab translational clinical trial for AI patients diagnosed with obesity-related cancer, to be implemented prior to surgical resection of the tumor. Program components have been developed with community input through semi-structured interviews and guidance from the sponsoring tribal health facility, the San Carlos Apache Healthcare Corporation. Patients preparing for cancer surgery will engage in a 3-week multimodal intervention that entails home-based exercise, supervised fitness sessions, promotion of anti-inflammatory foods, and health education materials adapted for and by community members. Serum and tissue biomarkers, as well as lifestyle behavioral measures, will be compared pre and post intervention to assess responsiveness. In respect of tribal sovereignty, the experimental procedure includes protocol refinement and approval by the tribal health facility’s IRB and tribal council.
Summary of Data. Our qualitative data reveal AI cancer survivors from the partnering tribal community have high interest in prehab and attest they would have participated if offered (100%). Their consensus feedback fashioned the specifics of the prehab translational clinical trial: 30 minutes daily walking, 60 minutes supervised resistance training twice weekly, 2 ounces walnut consumption daily, nutrition counseling, transportation assistance, and education/encouragement from staff and peers. Biospecimen sampling can be a sensitive topic for AI audiences, which we addressed early and found 75% of the interviewed survivors agreed to biospecimen collection without stipulation; this increased to 100% support once the rationale for biospecimens was explained.
Conclusions: Published prehab studies in other populations administered for 3-5 weeks between diagnosis and surgery have shown improvements in functional capacity, attenuation of surgery-induced losses, alterations of inflammatory biomarkers, and patient safety. Our community-informed prehab translational clinical trial for AI patients is the first of its kind, and anticipated to demonstrate feasibility, patient acceptability, behavioral changes in lifestyle, and the potential to modulate inflammatory biomarkers.
Citation Format: Jennifer Erdrich, Adriena Hernandez, Jennifer W. Bea, Cynthia A. Thomson. Bringing the first prehabilitation program to American Indian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 997.
Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia
Authors: Ross-Driscoll Katherine , Ayuk-Arrey Arrey-Takor , Lynch Raymond , McCullough Lauren E. , Roccaro Giorgio , Nephew Lauren , Hundley Jonathan , Rubin Raymond A. , Patzer Rachel 
Published: March 2024

Abstract

Liver transplantation offers the best survival for patients with early-stage hepatocellular carcinoma (HCC). Prior studies have demonstrated disparities in transplant access; none have examined the early steps of the transplant process. We identified determinants of access to transplant referral and evaluation among patients with HCC with a single tumor either within Milan or meeting downstaging criteria in Georgia.
Population-based cancer registry data from 2010 to 2019 were linked to liver transplant centers in Georgia. Primary cohort: adult patients with HCC with a single tumor ≤8 cm in diameter, no extrahepatic involvement, and no vascular involvement. Secondary cohort: primary cohort plus patients with multiple tumors confined to one lobe. We estimated time to transplant referral, evaluation initiation, and evaluation completion, accounting for the competing risk of death. In sensitivity analyses, we also accounted for non-transplant cancer treatment.
Among 1,379 patients with early-stage HCC in Georgia, 26% were referred to liver transplant. Private insurance and younger age were associated with increased likelihood of referral, while requiring downstaging was associated with lower likelihood of referral. Patients living in census tracts with ≥20% of residents in poverty were less likely to initiate evaluation among those referred [cause-specific hazard ratio (csHR): 0.62, 95% confidence interval (CI): 0.42–0.94]. Medicaid patients were less likely to complete the evaluation once initiated (csHR: 0.53, 95% CI: 0.32–0.89).
Different sociodemographic factors were associated with each stage of the transplant process among patients with early-stage HCC in Georgia, emphasizing unique barriers to access and the need for targeted interventions at each step.

Significance:
Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.
Versican Associates with Tumor Immune Phenotype and Limits T-cell Trafficking via Chondroitin Sulfate
Authors: Hirani Priyanka , McDermott Jacqueline , Rajeeve Vinothini , Cutillas Pedro R. , Jones J. Louise , Pennington Daniel J. , Wight Thomas N. , Santamaria Salvatore , Alonge Kimberly M. , Pearce Oliver M.T. 
Published: March 2024

Abstract

Immunotherapies for cancers of epithelial origin have limited efficacy, and a growing body of evidence links the composition of extracellular matrix (ECM) with the likelihood of a favorable response to treatment. The ECM may be considered an immunologic barrier, restricting the localization of cytotoxic immune cells to stromal areas and inhibiting their contact with tumor cells. Identifying ECM components of this immunologic barrier could provide targets that whether degraded in situ may support antitumor immunity and improve immunotherapy response. Using a library of primary triple-negative breast cancer tissues, we correlated CD8+ T-cell tumor contact with ECM composition and identified a proteoglycan, versican (VCAN), as a putative member of the immunologic barrier. Our analysis reveals that CD8+ T-cell contact with tumor associates with the location of VCAN expression, the specific glycovariant of VCAN [defined through the pattern of posttranslational attachments of glycosaminoglycans (GAG)], and the cell types that produce the variant. In functional studies, the isomers of chondroitin sulfate presented on VCAN have opposing roles being either supportive or inhibiting of T-cell trafficking, and removal of the GAGs ameliorates these effects on T-cell trafficking. Overall, we conclude that VCAN can either support or inhibit T-cell trafficking within the tumor microenvironment depending on the pattern of GAGs present, and that VCAN is a major component of the ECM immunologic barrier that defines the type of response to immunotherapy.

Significance:
The response to immunotherapy has been poor toward solid tumors despite immune cells infiltrating into the tumor. The ECM has been associated with impacting T-cell infiltration toward the tumor and in this article we have identified VCAN and its structural modification, chondroitin sulfate as having a key role in T-cell invasion.