Clinical Cancer Research最新文献

{"title":"Abstract PR003: Exploring the exposome impact in early-onset colon and rectal cancer using methylation scores","authors":"Silvana C.E. Maas, Iosune Baraibar, Lea Lemler, Maria Butjosa-Espín, Odei Blanco Irazuegui, Josep Tabernero, Elena Elez, Jose A. Seoane","doi":"10.1158/1557-3265.earlyonsetca25-pr003","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-pr003","url":null,"abstract":"The incidence of early-onset colorectal cancer (eoCRC) has risen worldwide, yet the drivers of this trend remain poorly understood. Directly investigating the exposome as a possible risk factor has been hindered by limited data availability, particularly beyond standard lifestyle factors, such as an unhealthy diet and smoking. To enable the study of a greater variety of exposome factors, we investigated the possibility of using DNA methylation as an indirect biomarker for the exposome. We derived methylation scores (MSs) for 29 exposures, including lifestyle, air pollution, and pesticides, based on published epigenome-wide association studies. These MSs were used to compare eoCRC and later-onset CRC (loCRC) tumors in The Cancer Genome Atlas (TCGA) Colon Adenocarcinoma cohort (31 eoCRC vs. 100 loCRC), followed by replication through meta-analysis across nine independent studies (83 eoCRC vs. 272 loCRC). For exposures within the selected 29 factors where direct measurements were available, MSs consistently reflected associations with measured exposures in tumor or blood profiles. Moreover, our approach successfully identified established risk factors for eoCRC, such as lower educational attainment, smoking, and non-Mediterranean dietary patterns, further validating the proposed methodology. Besides validating our proposed methodology, we identified picloram, an herbicide classified as IARC Group 3, as a potential novel risk factor. To address the limited methylation data on picloram, we integrated transcriptomic profiles from pluripotent stem cell–derived cardiomyocytes exposed to picloram. Differentially expressed genes under exposure were used to construct a picloram-specific single-sample GSEA (ssGSEA) score in TCGA-COAD, which showed significant correlation with the picloram-MS. At the population level, we further linked U.S. county-level eoCRC incidence from the SEER program to picloram application estimates (NAWQA Project, 1992–2012). This relationship remained significant after adjusting for socioeconomic indicators and other pesticide use. Together, these findings demonstrate the utility of MSs as effective proxies in exposome research and demonstrate their ability to uncover novel environmental risk factors. Beyond confirming known contributors, our study highlights picloram as a candidate exposure associated with eoCRC, supported by evidence across methylation, transcriptomic, and population data. These results underscore exposome differences between eoCRC and loCRC and suggest opportunities for prevention through exposome modification and regulatory policy. Citation Format: Silvana C.E. Maas, Iosune Baraibar, Lea Lemler, Maria Butjosa-Espín, Odei Blanco Irazuegui, Josep Tabernero, Elena Elez, Jose A. Seoane. Exploring the exposome impact in early-onset colon and rectal cancer using methylation scores [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"4 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B035: Multilevel Insights into Obesity, Race/Ethnicity, and Survival in Early-Onset Colorectal Cancer in Georgia","authors":"Meng-Han Tsai, Marlo Vernon, Malcolm Bevel, Humberto Sifuentes, Jorge Cortes, Rebecca L. Siegel","doi":"10.1158/1557-3265.earlyonsetca25-b035","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b035","url":null,"abstract":"Background: Early-onset colorectal cancer (EOCRC) is rising among adults aged 18–49, with Georgia showing particularly high mortality rates. Racial minorities (e.g., Black or Hispanic adults) in the state are more likely to face higher obesity rates and live in areas with limited access to healthy food and safe spaces for physical activity- factors that may hinder healthy lifestyle adoption and worsen cancer outcomes. However, most research on obesity and EOCRC mortality relies on either ecological or individual-level data and rarely examines changes in survival over time. By integrating county-level obesity rates into individual-level data, we evaluated how structural barriers affect cause-specific EOCRC survival across racial groups and time intervals in Georgia. Methods: We conducted a retrospective cohort study using data from the 2010-2020 Georgia Cancer Registry, linked with County Health Rankings. The primary exposures were race/ethnicity (White, Black, Hispanic/Other) and log-transformed county-level obesity rates (body mass index, [BMI] ≥ 30), categorized as low vs. high based on the median value. Outcome was survival time from diagnosis to 12, 36, and 60 months, censored at death from other causes or at the date of last contact. Traditional and piecewise Cox regression models were used, adjusting for sociodemographic characteristics (sex, age at diagnosis, marital status, insurance status, county-level rurality, and poverty), stage at diagnosis, and diagnosis year. Results: Among 6,291 EOCRC patients, 63.4% lived in high-obesity areas, and 53.3% were White patients. White patients living in high-obesity areas had significantly lower 3-year (76.6% vs. 81.1%; p=0.002) and 5-year (71.3% vs. 75.7%; p =0.001) survival rates compared to those in low-obesity areas. Survival differences were not observed for Black and Hispanic/Other patients. Adjusted analysis showed that patients living in high-obesity areas were 14% more likely to die from CRC than those living in low-obesity areas at both 3- (HR,1.14; 95% CI, 1.02-1.28) and 5-year (HR,1.14; 95% CI, 1.03-1.27) intervals, whereas White patients specifically were 32% (HR,1.32; 95% CI, 1.11-1.54) and 33% (HR,1.33; 95% CI, 1.13-1.50) more likely to die from CRC, respectively. Piecewise models revealed a 29% increased risk of CRC mortality within 1–3 years (HR,1.29; 95% CI, 1.11–1.50), with subgroup analysis showing an even higher 51% risk for White patients during the same interval (HR,1.51; 95% CI, 1.21–1.89). Conclusions: Distinct results between traditional and piecewise models suggest that mortality risk varies over time, with elevated risk in the first 1–3 years for White patients in high-obesity areas. These findings support targeted efforts to promote healthy lifestyles and invest in infrastructure that fosters healthier living to reduce early mortality. Finally, our study did not observe similar disparities among racial minorities due to limited sample size that could reduce the power to ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"30 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PR012: Transcriptomic and pathway analyses patterns in early-onset and late-onset microsatellite stable colorectal cancer: Results from the ORIEN Network","authors":"Sheetal Hardikar, Griffin Caryotakis, David A. Nix, Aaron Atkinson, Jamie Teer, Vaia Florou, Andreana Holowatyj, Michelle L. Churchman, David M. McKean, Phaedra Agius, Bodour Salhia, Ning Jin, Daniel Spakowicz, Micha Cavnar, Emily Baiyee. Toegel, Tiago Biachi de Castria, Patrick M. Boland, Ahmad Tarhini, Bryan P. Schneider, Matthew Reilley, Deepak Vadehra, Michele M. Gage, Howard Colman, Courtney Scaife, Jessica N. Cohan, Biljana Gigic, Adetunji Toriola, Christopher I. Li, Jane Figueiredo, Dorotha Byrd, David Shibata, Cornelia M. Ulrich, Aik Choo Tan, Erin M. Siegel","doi":"10.1158/1557-3265.earlyonsetca25-pr012","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-pr012","url":null,"abstract":"Introduction: Although ∼20% of early-onset colorectal cancer (EOCRC, age at diagnosis <50y) cases are due to germline mutations, the etiology of the majority of EOCRC cases remains poorly understood. EOCRC differs molecularly from late-onset colorectal cancer (LOCRC, age at diagnosis > 70y), with EOCRC tumors more frequently exhibiting high-grade histology, immune-related signatures, and microsatellite instability, while LOCRC is marked by DNA damage and oxidative stress pathways. Although consensus molecular subtypes (CMS) offer a framework for classification, they do not fully explain the rising EOCRC incidence, highlighting the need for integrative multiomic approaches to uncover underlying genetic, epigenetic, and environmental drivers for EOCRC. Methods: We leveraged genomic, transcriptomic, and clinical data from 1,135 sporadic microsatellite stable colorectal cancer (CRC) patients enrolled in the Total Cancer Care protocol and included in the Oncology Research Information Exchange Network (ORIEN) Avatar program across seven U.S. cancer centers, using standardized protocols for biospecimen collection, sequencing, and data harmonization. Whole exome sequencing (WES) and transcriptomic profiling (RNA-Seq) was conducted using standardized pipelines, followed by normalization and filtering. We characterized biological differences across EOCRC and LOCRC using differential expression, molecular subtyping, immune deconvolution, survival analysis, and integrated pathway analyses combining RNA-seq and WES data. Results: Our cohort included 27.8% EOCRC, 53.5% average-onset (50-69y) and 18.9% LOCRC cases. EOCRC patients were more likely to present with rectal tumors (24% vs. 14%), advanced stage (75% vs. 57%), and receive treatments at a higher proportion (radiotherapy: 35% vs. 23%; adjuvant therapy: 51% vs. 37%) compared to LOCRC. No significant differences were observed in common CRC mutations or tumor mutational burden. EOCRC cases were significantly enriched for the mesenchymal CMS4 subtype and depleted in CMS2 and CMS3 (p < 9.46 × 10-6), though 5-year survival did not differ by CMS (p-value=0.23). Notably, we observed that EOCRC cases with CMS2 or CMS4 were more likely to be overweight (BMI >= 25kg/m2) as compared to LOCRC (OR > 2). Transcriptomic analysis identified 328 differentially expressed genes (306 up-regulated and 22 down-regulated in EOCRC); GSEA analysis showed enrichment of Hedgehog and calcium signaling pathways (FDR < 0.1) in EOCRC. Conclusions: This comparison of EOCRC and LOCRC cases demonstrates clear differences in CMS subtypes, reveals specific associations with environmental factors, and suggests that calcium channel signaling and hedgehog signaling may play a crucial role in the development and progression of EOCRC compared to LOCRC. Citation Format: Sheetal Hardikar, Griffin Caryotakis, David A. Nix, Aaron Atkinson, Jamie Teer, Vaia Florou, Andreana Holowatyj, Michelle L. Churchman, ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"8 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B011: Associations between county-level air pollutants and early-onset breast cancer incidence rates in the U.S","authors":"Anna L. Fischer, Guoli Zhou, Kelly A. Hirko","doi":"10.1158/1557-3265.earlyonsetca25-b011","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b011","url":null,"abstract":"Purpose: The incidence of early-onset breast cancer, diagnosed before age 50 years, has increased significantly in the U.S. and globally in recent decades. While various genetic factors have been implicated in the development of early-onset breast cancer, the role of environmental exposures remains unclear. This study examined associations between ambient air pollution measures and early-onset breast cancer incidence rates in the U.S. Methods: We conducted an ecological analysis of county-level associations between particulate matter <2.5 micrometers (PM2.5) and Nitrogen Dioxide (NO2) exposures (averaged from 2002-2006) and age-adjusted early-onset breast cancer rates (averaged from 2017-2021), accounting for a potential latency period between exposure and diagnosis. The study included 1,422 U.S. counties with available data on pollutants and age-adjusted early-onset breast cancer incidence rates. Generalized additive models were used to estimate associations between pollutants (PM2.5 and NO2 ) and early-onset breast cancer incidence rates, adjusting for county-level prevalence of physical inactivity, college education attainment, poverty, and proportions of Hispanic and non-Hispanic Black populations. Results: After adjusting for confounders, PM2.5 was significantly inversely associated with early-onset breast cancer rates (Tertile 2 vs. Tertile 1: b = -1.66, p=0.01; Tertile 3 vs. Tertile 1: b = -1.85, p=0.01). Similar inverse associations were observed for NO2 (Tertile 2 vs. Tertile 1: b = -1.97, p<0.01); Tertile 3 vs. Tertile 1: b=-2.59, p<0.01). A significant non-linear association between PM2.5 (per 10-unit increase) and early-onset breast cancer rates was detected (estimated degrees of freedom (EDF) = 3.2, p=0.014), with rates increasing up to approximately 10 mcg/m3, then declining at higher concentrations. Conclusion: These findings suggest inverse associations between higher tertiles of PM2.5 and NO2 exposure and early-onset breast cancer rates. However, the observed non-linear relationship between PM2.5 and early-onset breast cancer indicates a possible threshold effect or residual confounding at higher PM2.5 exposure levels. These results underscore the complexity of modeling environmental risk and highlight the need for further research to confirm these findings and investigate underlying biological mechanisms for potential threshold effects. If confirmed, the findings suggest that public health interventions to mitigate air pollution should also target areas with intermediate levels of pollution. Citation Format: Anna L. Fischer, Guoli Zhou, Kelly A. Hirko. Associations between county-level air pollutants and early-onset breast cancer incidence rates in the U.S [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr B","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"1 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B037: Early-Onset Cancer: A Focus on Pregnancy-Associated Cases","authors":"Nicole C. Loroña, Jenny Harris, Jane C. Figueiredo","doi":"10.1158/1557-3265.earlyonsetca25-b037","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b037","url":null,"abstract":"Background: Recent data in the U.S. show a rising rate of early-onset cancers (diagnosed before age 50) over the past decade, with the largest increase in rates seen in the 30-39 age group and the highest number of cases in the 40-49 age group. Simultaneously, the maternal age at the time of pregnancy has increased, with 38% of first births now occurring in women aged 30 and older. The increasing incidence of early-onset cancer, coupled with increasing maternal age, could result in more cancers diagnosed during pregnancy or postpartum. The present study describes trends in the incidence of cancer during pregnancy and postpartum and identifies predictors of pregnancy-associated cancers. Methods: We identified cancer cases diagnosed in adults from 2015 to 2023 with at least one health encounter in the time frame in a large health system in the greater Los Angeles area. We identified patients with obstetric International Classification of Diseases (ICD-10) codes and/or oncology notes mentioning pregnancy in the two years before and six months following the patient’s date of cancer diagnosis. Pregnancy-associated cancer was defined as a diagnosis during pregnancy or within two years postpartum (following any birth, miscarriage, or ectopic pregnancy). Descriptive statistics characterized demographic and cancer-related factors. Results: Among 40,432 patients with cancer during the study period, we identified 217 pregnancy-associated cancers in 216 patients [one individual had thyroid cancer diagnosed following a pregnancy, and breast cancer in a subsequent pregnancy]. Median age at cancer diagnosis was 37 (range: 24-50). 13% of patients were Asian, 6% were Black or African American,15% were Hispanic, and 56% were non-Hispanic White. The majority (n=193, 92%) of pregnancy-associated cancers were solid tumors (vs. 8% hematological), of which the most common sites were breast (N=85, 44%), thyroid (N=35, 18%), cervix (N=13, 7%), central nervous system (N=11, 6%), ovarian (N=8, 4%) and colon (N=6, 3%). Most solid tumors were diagnosed at early stages (50% stage I, 21% stage II vs. 11% stage III, 9% stage IV), with 15 in situ cancers diagnosed (6 breast cancer, 6 gynecologic malignancies, and 3 melanoma). 60 cancers were diagnosed during pregnancy (33% breast and 13% thyroid cancer), 91 during one year postpartum (32% breast and 20% thyroid cancer), and 66 between one and two years postpartum (55% breast and 14% thyroid cancer). Analyses of the total incidence of and predictors of pregnancy-associated cancer are ongoing. Conclusions: Pregnancy-related cancers present challenges for maternal-fetal care and oncology. The two-year interval postpartum may represent a key window for surveillance and earlier diagnosis. Identifying predictors, treatment patterns, and risk factors for adverse outcomes will help develop screening strategies to diagnose pregnancy-related cancer early and improve clinical management of these cases. Citation Format: Nicole C. Loroña, Je","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"1 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B029: Clinical and Sociodemographic Associations Between Early-Onset and Late-Onset Colorectal Cancer in a U.S.–Mexico Border Population","authors":"Atharva Railkar, Amir Hernandez, Jennifer Molokwu","doi":"10.1158/1557-3265.earlyonsetca25-b029","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b029","url":null,"abstract":"Colorectal cancer (CRC) is the second leading cause of cancer mortality for both men and women in the United States. While the general incidence of CRC among older adults has decreased since the 1990s, CRC incidence in younger adults has increased during the same time span. Surveillance data specifically reveal a hotspot of CRC incidence along the U.S.-Mexico border near El Paso, Texas, with an upward trend even as statewide rates have plateaued. Despite these observed disparities, there is limited data on early-onset CRC patterns in border communities. This study is a secondary analysis of data derived from a case-control study conducted between 2011 and 2023 to describe the health status of an outpatient population in El Paso, Texas. The sample population (n = 818) was identified from patients in the parent study who were cases and had a CRC diagnosis. This study investigated differences in the health status, comorbidities, and biomarkers in individuals diagnosed with CRC before age 50 (early-onset, EO-CRC) and those diagnosed at or after age 50 (late-onset, LO-CRC) in a predominantly Hispanic population along the U.S.-Mexico border. Results indicated that EO-CRC patients had higher rates of being uninsured (22.6%), having private insurance (54.1%), and reporting higher household incomes (p = 0.047). They were also more likely to have metastatic cancer (OR: 0.650; 95% CI: 0.457, 0.925; p = 0.016) and to have a family history of cancer (OR: 0.276; 95% CI: 0.117, 0.652; p = 0.002). In contrast, LO-CRC patients exhibited greater comorbidity burden, including significantly higher prevalence of heart failure, hypertension, renal failure, and type II diabetes. LO-CRC patients were also more likely to have been prescribed medications such as aspirin (OR: 5.472; 95% CI: 2.819, 10.618; p < 0.001) and statins (OR: 3.470; 95% CI: 2.092, 5.758; p < 0.001). Biomarker analysis revealed that EO-CRC patients had higher aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, and alkaline phosphatase levels compared to LO-CRC patients, while LO-CRC patients had higher blood urea nitrogen, creatinine, glucose, and potassium levels. These findings underscore meaningful clinical and demographic distinctions between EO-CRC and LO-CRC that may reflect unique etiologic pathways, access challenges, and behavioral factors. Younger CRC patients tended to have lower Elixhauser risk scores and fewer comorbidities, which aligns with previous studies suggesting that EO-CRC patients may otherwise be relatively healthy at diagnosis. The higher metastatic burden among younger patients adds urgency to improving symptom recognition in younger adults. It suggests that existing screening and diagnostic models may miss warning signs in younger populations. As EO-CRC incidence increases, particularly among Hispanic populations, targeted, age-sensitive approaches to prevention, diagnosis, and care are essential for improving outcomes and reducing ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"13 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A035: A complex clinical evolution: Mediastinal unicentric Castleman disease preceding paraneoplastic pemphigus and bronchiolitis obliterans","authors":"Chase V. West, Humberto R. Nieves-Jiménez, Matthew Washko, Ahmed Alderazi, Mohannad Safadi, Saadia A. Faiz","doi":"10.1158/1557-3265.earlyonsetca25-a035","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-a035","url":null,"abstract":"Castleman disease (CD) is a rare condition characterized by lymph node hyperplasia and immune dysregulation, often presenting as a spectrum of disorders rather than a single entity. Although not a malignancy in the traditional sense, CD exhibits overlapping neoplastic features, creating diagnostic and therapeutic challenges. It is classified as either a localized (unicentric) or diffuse (multicentric) process, with unicentric CD (UCD) presenting at a younger age. We present a UCD case complicated by paraneoplastic pemphigus (PNP) and bronchiolitis obliterans (BO), demonstrating the diagnostic complexity and importance of prompt recognition and treatment. An asymptomatic 38-year-old woman was referred for evaluation of a 7.2-cm middle mediastinal mass adjacent to the trachea initially noticed abroad. The patient underwent CT-guided core needle biopsy which demonstrated reactive lymphoid tissue and an expanded paracortex, and was initially monitored without intervention. Within two months, she developed an intermittent dry cough with shortness of breath (SOB), for which empiric antibiotics and low-dose steroids were prescribed for presumed respiratory infection, although to no resolution. The patient was evaluated by pulmonology, in which pulmonary function testing revealed a fixed obstructive pattern. Concurrently, painful oral ulcers were evaluated by oral surgery, and buccal biopsy specimen showed microscopic and direct immunofluorescence findings concerning for PNP. Subsequent dermatologic evaluation included a PNP antibody panel which confirmed desmoglein-3 and envoplakin antibodies. Given worsening SOB and dyspnea at rest, the patient presented to the emergency department, and CT chest demonstrated tapering of multiple distal bronchi with hyperlucency of the lungs, consistent with BO. She was admitted and started on high-dose steroids (methylprednisolone 1g/day ×3 days), in addition to intravenous immunoglobulin (IVIG) (2 g/kg total), endorsed by rheumatology. As the mass was considered the primary driver of the paraneoplastic process, cardiothoracic surgery successfully resected the now-enlarged 9.1-cm mediastinal lesion; pathology confirmed hyaline-vascular CD. The patient experienced an uncomplicated postoperative recovery. After five days of observation, the patient denied SOB, weakness or fatigue, and was saturating comfortably on room air. A total of four cycles of IVIG were completed, and a long-term steroid taper was issued, along with appropriate Pneumocystis jirovecii pneumonia and gastrointestinal prophylaxis. This case underscores the importance of early recognition and treatment of CD. Despite its rarity, the tendency of the disease to affect younger patients emphasizes the need for a high index of suspicion when evaluating nonspecific systemic manifestations. The presence of a single mass can mimic multiple other etiologies, complicating the clinical picture and potentially delaying diagnosis. A comprehensive assessment coupled ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"7 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B015: Impact of sun sensitivity and ultraviolet radiation on the association between blistering sunburns and keratinocyte carcinoma","authors":"Belinda L. Gorsuch, Jim Z. Mai, Martha S. Linet, Michael R. Sargen, Mark P. Little, Bruce H. Alexander, Cari M. Kitahara, Elizabeth K. Cahoon","doi":"10.1158/1557-3265.earlyonsetca25-b015","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b015","url":null,"abstract":"Importance Given the large and growing burden of keratinocyte carcinomas (KCs) in the United States, there is a pressing need to identify individuals at high risk. Objective To quantify the association between KC risk and history of blistering sunburns in childhood and adulthood and to investigate whether individual sun sensitivity and other measures of ultraviolet radiation modify these associations. Design We examined blistering sunburns and KC risk in the nationwide U.S. Radiologic Technologists cohort study. Baseline data (1983-2005) on lifetime sunburn history and sun sensitivity traits were collected via self-administered questionnaires. Participants were followed until the diagnosis of a first primary cancer or completion of a follow-up questionnaire (2012-2014). Setting United StatesParticipants Radiologic technologists without a prior cancer who reported White race or Hispanic ethnicity and completed both the baseline and follow-up questionnaires. Exposures History of blistering sunburns before (childhood) and after (adulthood) age 15 years. Main Outcomes and Measures Risk increase for basal and squamous cell carcinoma (BCC/SCC) per blistering sunburn. Results Among 40,204 radiologic technologists (2% Hispanic; mean age at baseline:56 years), those reporting at least one blistering sunburn had a 37% higher risk of BCC and a 41% higher risk of SCC. The risk of BCC increased by 6% (95% confidence interval [95% CI], 5-7) and 5% (95% CI, 4-6) for each childhood and adulthood blistering sunburns, respectively. Similar findings were observed for SCC, with risk increasing by 8% (95% CI, 6-11) and 7% (95% CI, 5-9) for childhood and adulthood blistering sunburns, respectively. These associations were not significantly modified by most individual sun sensitivity traits and other measures of ultraviolet radiation. Conclusions and Relevance Individuals with ≥5 blistering sunburns occurring across varying ages of exposure appear to be at particularly high risk for KCs and may benefit from heightened skin cancer surveillance. Citation Format: Belinda L. Gorsuch, Jim Z. Mai, Martha S. Linet, Michael R. Sargen, Mark P. Little, Bruce H. Alexander, Cari M. Kitahara, Elizabeth K. Cahoon. Impact of sun sensitivity and ultraviolet radiation on the association between blistering sunburns and keratinocyte carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr B015.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"29 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract C021: Characterizing the clinicopathological, genomic and spatial transcriptomic features of colibactin-induced colorectal cancers","authors":"Peter Georgeson, Jihoon E. Joo, Alysha Prisc, Lochlan Fennell, Liam Skinner, Bernard J. Pope, Khalid Mahmood, Romy Walker, Mark Clendenning, Julia Como, Natalie Diepenhorst, Julie McDonald, Finlay A. Macrae, Christophe Rosty, Ingrid M. Winship, Amanda Phipps, Mark A. Jenkins, Ulrike Peters, Daniel D. Buchanan","doi":"10.1158/1557-3265.earlyonsetca25-c021","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-c021","url":null,"abstract":"Introduction: Colorectal cancers (CRCs)with related colibactin-induced DNA damage from pks+E.coli bacteria are identified by the presence of the SBS88 tumor mutational signature and mutations in unique 5bp genomic contexts (extended contexts). CRCs with high SBS88 and high extended contexts (colibactin-positive) remain poorly characterized in terms of identifying distinct clinicopathological, genomic, and transcriptomic features. Methods: We applied a mutational signature-based classifier derived from organoid sequencing data to identify colibactin-positive CRCs in 1,716 non-hereditary, microsatellite stable (MSS) whole-genome sequenced primary tumors from Genomics England (GEL). Clinicopathological, genomic and survival associations were tested in an independent cohort of 4,254 primary MSS CRCs from the GECCO-CCFR consortium. Spatial transcriptomic profiling of the tumor microenvironment of colibactin-positive EOCRCs was performed using Nanostring CosMx technology. Results: Colibactin-positive CRCs were identified in 10.2% (175/1,716) of the GEL CRCs and were associated with an early age at diagnosis (<40 years: 4.0% of positives v 2.0% of negatives; p=0.1), enrichment in patients born on or after 1980 (6.9% v 1.4%; p=0.02), and location in distal colon and rectum compared with proximal colon (45%/47% v 41%/28% distal/rectum; p=5x10-11) when compared with the colibactin-negative CRCs (n=1,400, 81%). Genomic analysis revealed recurrent mutations in established CRC driver genes, the strongest of which were APC:c.835-8A>G (p=1x10-12), SMAD4:c.788-8A>G (p=0.0001) and BRAF:c.1781A>G (p=0.001), with mutations exhibiting site-specificity. Colibactin-positive CRCs exhibited distinctive large-scale genomic alterations, including recurrent loss of heterozygosity spanning TGIF1, SMAD2, DCC, and SMAD4 gene region. Mutation timing analysis revealed that SBS88-associated mutations, extended context mutations and APC:c.835-8A>G are early, clonal events (p=3x10-35, 7x10-81, 3x10-9 respectively). In the GECCO-CCFR CRCs, 5.1% of 4,254 MSS CRCs were identified as colibactin-positive (216 of 4,254) with similar significant genomic hallmarks: earlier age at diagnosis (<50 years p=0.03), distal and rectum site (p=4x10-9), and recurrent mutations in APC, SMAD4 and BRAF (p=4x10-128, 2x10-9, 2x10-8). Spatial transcriptomic profiling of six EOCRCs (three colibactin-positive) obtained 1.5 million cells across 19 cell types. Our preliminary analyses identified distinct stromal and immunological profiles associated with colibactin-positive EOCRCs. Conclusions: A combined SBS88 and extended context mutational signature-based classifier for colibactin-induced DNA damage, identified a distinct subtype of CRC characterized by earlier age at diagnosis, distal and rectal site predominance, specific somatic mutations, and unique genomic instability patterns. These findings provide new insights into colibactin-mediated carcinogenesis and cr","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"5 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B006: Early-onset colorectal cancer: 10 year review of histopathological trends in a tertiary hospital in Accra, Ghana","authors":"Barbara ADJEI-MENSAH, PATIENCE PEPRA-AMEYAW","doi":"10.1158/1557-3265.earlyonsetca25-b006","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b006","url":null,"abstract":"Objective: Colorectal cancer (CRC) ranks 8th in cancer-related mortality in Ghana. Globally, it is the third most common cancer and second in cancer-related deaths. Early-onset colorectal cancer (EOCRC), defined as CRC occurring before age 50, is rising. This study reviews the prevalence of EOCRC, the histological grade, and pathological stage at tumour resection. Methods: A retrospective analysis of histopathology records at the Pathology Department, Korle Bu Teaching Hospital, Accra was conducted. Colorectal cancer cases diagnosed between 2015 and 2024 were reviewed. Data on patients aged 18–49 were extracted and analysed using STATA 14. Results: Over the ten-year review period, 44 cases of early-onset colorectal cancer (EOCRC) were diagnosed following surgical resection, representing 22.6% of all colorectal cancer diagnoses during the same period. The male-to-female ratio was 1.3 to 1, indicating a slight male predominance. Most patients were between 40 and 49 years old, accounting for 47.7% of cases. The least diagnoses were recorded in the 20 to 29 age group, comprising only 11.4%. Histologically, 50% of the tumors were classified as well-differentiated adenocarcinomas. Moderately differentiated adenocarcinomas accounted for 45.5%, while 6.8% were poorly differentiated. According to the TNM classification, 18.2% of tumors were staged as T2, indicating invasion of the muscularis propria. A larger proportion, 47.7%, were T3 tumors- the tumor had invaded the subserosa or non-peritonealized pericolic or perirectal tissues. T4 tumors, which invade adjacent organs or perforate the visceral peritoneum, made up 34.1% of the cases. 54.5% of patients had no regional lymph node metastasis (N0). About 15.9% had metastases in one to three lymph nodes (N1), while 25% had involvement of four or more regional lymph nodes (N2). In 4.5% of the cases, lymph node status could not be assessed (NX). Conclusion: Over one in five colorectal cancer cases occurred in individuals under 50, and mostly presenting at advanced local tumour stages. These findings highlight the need for increased awareness and early screening for CRCs in Ghana. Citation Format: barbara adjei- mensah, patience pepra- ameyaw. Early-onset colorectal cancer: 10 year review of histopathological trends in a tertiary hospital in Accra, Ghana [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr B006.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"56 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}