Clinical Cancer Research最新文献

{"title":"Abstract B002: Addressing knowledge gaps in early-onset cancers: Radiological insights into oncogenic-immune dynamics of anaplastic Wilms tumors","authors":"Xiaoping Su, Ying Yuan, Gabriel Malouf","doi":"10.1158/1557-3265.earlyonsetca25-b002","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b002","url":null,"abstract":"This study investigates the intricate interplay between oncogenic pathways and the immune microenvironment in anaplastic Wilms tumors (AWTs) and explores its radiological implications. AWTs, characterized by complex genetic alterations including TP53 and CTNNB1 mutations, exhibit a unique immunophenotype with implications for tumor-immune dynamics. Leveraging comprehensive genomic profiling and immunological markers, we analyze how these interactions influence the radiological presentation of AWTs. We performed whole-exome and/or RNA sequencing on genomic DNA derived from 12 matched tumor-normal WTs and extended analysis in an independent dataset of 9 cases. Leveraging comprehensive genomic profiling and immunological markers, we analyzed how these interactions influence the radiological presentation of AWTs. The delicate equilibrium between pro-tumorigenic and anti-tumorigenic immune elements is examined, emphasizing the potential of advanced imaging modalities to capture evolving tumor-immune interactions. Immune infiltrates, such as lymphocytes and myeloid cells, are assessed for prognostic value and radiological correlates. The study aims to identify radiomic features that correlate with the immunological landscape, providing radiologists with tools for risk stratification and treatment response prediction. This research sheds light on the complex interplay between oncogenic signaling and the immune system in AWTs, offering radiologists insights to enhance diagnostic accuracy and therapeutic monitoring. Integration of genomic, immunological, and radiological data holds promise for developing tailored imaging strategies, contributing to a comprehensive understanding of AWT biology and facilitating personalized therapeutic interventions. Citation Format: Xiaoping Su, Ying Yuan, Gabriel Malouf. Addressing knowledge gaps in early-onset cancers: Radiological insights into oncogenic-immune dynamics of anaplastic Wilms tumors [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 B002.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"17 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717314","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 B034: Sex and Racial Disparities in Time to Treatment for Early-Onset Colorectal Cancer Across a Four-Level Rurality Classification in the United States","authors":"Meng-Han Tsai, Steven Coughlin, Kenneth J. Vega","doi":"10.1158/1557-3265.earlyonsetca25-b034","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b034","url":null,"abstract":"Background: Adults with early-onset colorectal cancer (EOCRC, diagnosed at age < 50 years) often face diagnostic delays, making timely treatment essential for optimal outcomes. Evidence shows that male patients and racial/ethnic minorities, especially those in socioeconomically disadvantaged areas, are more likely to experience treatment delays. However, limited studies have explored how sex, racial, and geographic disparities influence treatment timeliness. This study addresses that gap by examining time to treatment across three post-diagnosis intervals, while accounting for a four-level rurality classification. Methods: We conducted a retrospective cohort analysis using the 2006–2020 Incidence Data with Census Tract Attributes from the Surveillance, Epidemiology, and End Results Program. The primary exposures included sex, race (White, Black, Hispanic, American Indian/Alaska Native [AI/AN], and Asian/Pacific Islander [Asian/PI]), and rurality (all urban, mostly urban, mostly rural, all rural). The outcome was time to treatment, categorized as initiation within 30, 60, or 90 days from diagnosis. Patients were censored if treatment was not initiated or occurred beyond the specified timeframes. Cox proportional hazards models were used, adjusting for sociodemographic, clinical factors, and diagnosis year. Multiple imputation addressed missing treatment time data (14.3%, n = 11,312). Results: Among 79,090 EOCRC patients, the average time to treatment was 20 days (SD = 32.4; IQR = 30), the shortest in mostly rural areas (17.8 days), followed by all rural (18.3 days), mostly urban (19.1 days), and all urban areas (20.7 days) (p < 0.001). In the imputed model, male patients were 5% less likely to initiate treatment across all time intervals compared to females (p < 0.05). Hispanic and Asian/PI patients were 4% (95% CI: 0.93–0.99) and 7% (95% CI: 0.91–0.95) less likely, respectively, to receive treatment within 90 days. Conversely, patients residing in non–fully urban areas were 9%–12% more likely to receive treatment across all timeframes (p < 0.05). Stratified analyses further showed that male patients in all urban areas were consistently about 5% less likely to initiate treatment (p < 0.05). Black (HR: 0.95; 95% CI: 0.92–0.98), Hispanic (HR: 0.93; 95% CI: 0.91–0.95) and Asian/PI patients (HR: 0.96; 95% CI: 0.93–0.99) patients in fully urban areas were less likely to receive treatment within 90 days, with similar patterns observed at 30 and 60 days. Conclusions: Although most patients (∼88%) initiated treatment within 30 days of diagnosis, our findings reveal persistent-albeit modest-inequities in access. Male, Hispanic, Asian/PI, and Black patients were slightly more likely to experience delays, particularly beyond 90 days. Those patients in fully urban areas also faced greater delays, suggesting potential strain on urban healthcare systems and highlighting the need for further investigation. These insights can in","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"145 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717346","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 C018: Urinary Arsenic and Other Heavy Metals in Gallbladder Cancer Patients: A Pilot Study Correlating Exposure with Drinking Water and Assessing Carcinogenic Risk in Northeast India","authors":"Christy Thomas, Gaurav Das, Munlima Hazarika, Nilotpal Saharia, Krishna Undela","doi":"10.1158/1557-3265.earlyonsetca25-c018","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-c018","url":null,"abstract":"Introduction: Gallbladder cancer (GBC) incidence is disproportionately high in Northeast India, and the second most affected epidemiological region in the world, where the contribution of environmental factors like heavy metals remains understudied. Aims: To investigate the association between exposure to arsenic and other heavy metals in drinking water and urine with the risk of gallbladder cancer. Methods: This cross-sectional study, with institutional ethical approval, included 201 histopathologically confirmed GBC patients from a tertiary cancer hospital in Northeast India. Spot urine samples (N=201) and paired drinking water samples (N=100) were analyzed for twelve metals using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The analytical method was validated for precision (%RSD < 5%) and accuracy (85–109%). Statistical analysis involved non-parametric tests (Mann-Whitney U, Kruskal-Wallis) and Spearman's correlation, with health risks assessed using the US EPA model. Results: Urinary analysis of 201 patients revealed high mean concentrations of selenium (83.51 µg/L), strontium (84.40 µg/L), and arsenic (20.97 µg/L). In 100 drinking water samples, arsenic levels reached a maximum of 476.38 µg/L (48 times the WHO limit), while lead and nickel exceeded safety thresholds in 22% and 18% of samples, respectively. The total carcinogenic risk was 400-fold higher than EPA safety limits (4.0 × 10-3), and the non-carcinogenic Hazard Index (HI) from urine was 3.51, primarily driven by arsenic (HQ=2.44). Significant positive correlations were observed between urinary arsenic-selenium (r=0.504, p<0.01) and cadmium-selenium (r=0.552, p<0.01). Females exhibited significantly higher urinary concentrations of vanadium, chromium, and nickel (p<0.05). Fish consumption and smoking were found to significantly influence metal accumulation. Conclusions: This study provides novel evidence directly linking multi-metal exposure, particularly from contaminated drinking water to the risk of GBC. The findings underscore an urgent need for public health interventions focused on improving water quality, specifically targeting arsenic, and for further longitudinal research to confirm a causal relationship between heavy metal exposure and GBC. Citation Format: Christy Thomas, Gaurav Das, Munlima Hazarika, Nilotpal Saharia, Krishna Undela. Urinary Arsenic and Other Heavy Metals in Gallbladder Cancer Patients: A Pilot Study Correlating Exposure with Drinking Water and Assessing Carcinogenic Risk in Northeast India [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 C018.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"10 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717384","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 IA003: Trends in cancer mortality in young adults in selected upper-middle and high-income countries with focus on colorectal cancer: an update to 2026.","authors":"Carlo La Vecchia, Silvia Mignozzi, Claudia Santucci","doi":"10.1158/1557-3265.earlyonsetca25-ia003","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-ia003","url":null,"abstract":"An increasing incidence, but also mortality, from colorectal cancer (CRC) in young adults, i.e. in more recent generations, has been reported in several high-income countries over the last decade. We updated trends in cancer mortality in 15 countries (plus the EU) and predicted the number of deaths and rates for 2026, with focus on CRC. We analysed mortality data from the WHO dataset at age 25–49 in the 15 most populous upper-middle and high-income countries providing valid data from 1990 to 2022 or the latest available year – plus the EU. We derived population estimates from the UN World Population Prospects database. We computed age-standardised mortality rates (ASMR, world standard) for all cancers combined and for the most common sites in young adults (colorectum, lung, pancreas and breast). For CRC, we also computed ASMR for the 30–39 age group. We compared the ASMRs around 2020 with those around 2010. We performed a Joinpoint regression on all cancers combined and on the most common sites, over the period 1990-2022. We predicted the number of deaths for 2026 based on a log-linear regression model applied on the most recent segment identified through Poisson Joinpoint regression. Around 2020, the highest overall cancers rates were in Latin America and Eastern Europe (over 35/100,000 females, 25/100,000 males), while the lowest ones were in the Republic of Korea, Canada, and Japan (below 20/100,100 in both sexes). Between 2010 and 2020, all countries showed declines in total cancer mortality (by 10% to above 25% in both sexes), except Mexico and Argentina for females. However, CRC mortality increased appreciably in the UK (by about 30%) and in Northern and most Latin America (by about 10%), though it declined in most Europe, Japan, and the Republic of Korea. When the analysis was restricted to the 30–39 age group, i.e. the generation born in the 1980’s, substantial increases in CRC mortality were observed over the last decade in the UK, North and Latin America, and Australia, and to a lesser extent in Europe and Japan. Mortality tended to decrease for pancreatic and to a greater extent for lung and breast cancer in most countries. Thus, overall cancer mortality in young adults declined in the countries considered. This is mainly due to tobacco control for lung - with substantial declines proportionally similar for both sexes - and pancreatic cancer, as well as for other tobacco-related neoplasms. Improved diagnosis and treatment had a key role on favourable trends of breast cancer and several other neoplasms common in young adults. However, CRC mortality in young adults increased in several, but not all, countries considered. The increase was proportionally greater at age 30-39, i.e. among the generation born in the 1980’s compared to that born in the late 1970’s. The rising CRC mortality rate can be due to the increased prevalence of overweight, obesity, and consequently diabetes, but other (dietary) factors may be involved. This therefore d","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"240 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717474","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 C007: Age-stratified insight into genomic alterations in colon adenocarcinoma via AACR GENIE v18.0","authors":"Johnathan D. DeBetta, Ashani T. Weeraratna, Elizabeth M. Jaffee, Daniel J. Zabransky","doi":"10.1158/1557-3265.earlyonsetca25-c007","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-c007","url":null,"abstract":"Background: The incidence of colon cancer is rising more rapidly in patients under 50 years of age (early-onset colon cancer; EOCC) than in any other age group. This trend is likely a consequence of multifactorial causes, including environmental exposures, shifts in lifestyle factors, and expanded use of screening tests which are now recommended for individuals starting at age 45. However, fully defining the genomic landscape and understanding the biological mechanisms driving colorectal cancer in younger patients remains an ongoing effort. Methods: Genomic sequencing data from primary tumors diagnosed as colon adenocarcinoma were obtained from AACR Project GENIE Cohort v18.0, comprising 7,633 total patients, and accessed through the Synapse and cBioPortal platforms. Patients were grouped into EOCC (<50 years) and traditional-onset colon cancer (≥50 years). To better delineate aging-associated differences, we performed additional analyses using more restrictive age cutoffs of ≤45 years (n=1,267 patients) and ≥55 years (n=4,676 patients) for the respective groups. The clinical variable “Age at Which Tumor Sequencing Was Reported (Years)” was used as a proxy for “age at diagnosis.” Genes enrichments with fewer than 10 patients were excluded from this analysis. Results: The total cohort included 49.8% male (n=3801), 46.7% female (n=3563), and 3.5% patients of unknown sex/gender (n=269). Evaluation of the rate of patient-level genomic alterations between age groups revealed enrichment of mutations in APC (71.53% vs 63.95%, q-value 1.895e-4), TP53 (70.74% vs 64.68%, q-value 6.248e-3), TCF7L2 (16.48% vs 12.46%, q-value 0.0314), CTNNB1 (9.6% vs 6.15%, q-value 4.746e-3), and MSH2 (6.29% vs 3.81%, q-value 0.0211) in patients with EOCC. In comparison, mutations in BRAF (19.58% vs 8.2%, q-value 1.20e-21), RNF43 (17.06% vs 9.07%, q-value 3.25e-8), ZNRF3 (8.75% vs 3.55%, q-value 4.529e-3), SMARCA4 (9.2% vs 5.55%, q-value 7.461e-3), HLA-B (6.53% vs 3.03%, q-value 0.0269), AMER1 (10.18% vs 6.37%, q-value 0.0321), GNAS (4.08% vs 2.25%, q-value 0.0366), and HNF1A (4.62% vs 2.41%, q-value 0.0211) were enriched in traditional-onset colon cancer. Assessment of individual point mutations revealed enrichment of BRAF V600E (15.81% vs 4.42%, q-value 4.10e-29), KRAS Q61K (0.94% vs 0.08%, q-value 0.0446), and RNF43 G659Vfs*41 (10.16% vs 3.93%, q-value 1.12e-8) in traditional-onset colon cancer. Lastly, assessment of CNA amplifications revealed enrichment of NCOA3 (5.65% vs 2.28%, q-value 0.0276) in EOCC. Conclusion: We have identified novel associations between genomic alterations and patient age in colon cancer using AACR GENIE v.18, the largest public cancer genomic dataset available to date. Our findings reveal alterations not previously characterized in this age group, suggesting that EOCC may represent a biologically distinct disease entity rather than an earlier manifestation of traditional colon cancer. Further investigation into divergent molecular phenotyp","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"26 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717315","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 A028: Exploring exposure to and metabolism of polycyclic aromatic hydrocarbons (PAHs) in patients with cancer predisposition syndromes (CPS): research in progress","authors":"Judy Ou, Nancy Daher, Jennie Vagher, Casey Mehrhoff, Luke Maese","doi":"10.1158/1557-3265.earlyonsetca25-a028","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-a028","url":null,"abstract":"Background: Cancer predisposition syndromes (CPS) like Li-Fraumeni syndrome increase lifetime cancer risk up to 100% and leave patients susceptible to DNA damage from environmental carcinogens. Polycyclic aromatic hydrocarbons (PAHs) are carcinogens and global health hazards. Populations are exposed by inhaling airborne PAHs and ingesting grilled, smoked, barbecued, and fried foods. PAHs become carcinogenic when they are metabolized. These metabolites form DNA adducts and cause mutations in the P53 oncogene, which accelerates tumor development. This mechanism is highly relevant to patients with Li-Fraumeni syndrome that have altered P53 function. While activation of the aryl hydrocarbon receptor generally initiates the formation of PAH metabolites, new in vitro studies report that the metabolism of PAHs and the formation of subsequent PAH-DNA adducts is affected by a P53-related pathway. This may alter the metabolism of PAHs and risk for PAH-associated cancers in patients with Li-Fraumeni syndrome. Aim: We aim to assess the impact of PAH exposure on PAH metabolites in urine among CPS patients with and without Li-Fraumeni syndrome. Methods: We are implementing a pilot study that will recruit a sample of patients (n=20) from a CPS clinic at Huntsman Cancer Institute (HCI) in Utah, which has the nation’s largest nonsmoking population and among the highest releases of air toxics including carcinogenic PAHs. Over a 48 hour period, participants will wear passive samplers to measure airborne PAHs and report their diet. At the end of the observational period, participants will provide a urine sample and complete a survey that includes items about demographics and other lifestyle questions. We will describe exposure to PAHs according to demographics and compare correlations between exposure to PAHs and levels of excreted PAH metabolites between patients with and without Li-Fraumeni syndrome. Anticipated results: We anticipate that correlation coefficients between each unit of airborne PAH exposure or frequency of consumption of grilled, smoked, barbecued, and fried foods and the outcome of PAH urinary metabolites will be lower among Li-Fraumeni patients than non-Li-Fraumeni patients. Citation Format: Judy Ou, Nancy Daher, Jennie Vagher, Casey Mehrhoff, Luke Maese. Exploring exposure to and metabolism of polycyclic aromatic hydrocarbons (PAHs) in patients with cancer predisposition syndromes (CPS): research in progress [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 A028.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"40 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717342","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 B013: Epidemiology of early-onset gastrointestinal cancers in Nepal: A scoping review","authors":"Saroj GC, Bishal Paudel","doi":"10.1158/1557-3265.earlyonsetca25-b013","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b013","url":null,"abstract":"Introduction: The incidence of early-onset gastrointestinal cancers (EO-GICs, diagnosed <50 years) is rising globally. Low- and middle-income countries such as Nepal face distinct exposures that might influence the disease patterns in younger populations. However, systematic evidence on EO-GICs in these settings is limited. This scoping review aimed to map the available evidence on EO-GICs from Nepal and identify gaps to guide future research and early detection strategies. Methods: This scoping review adhered to the PRISMA-ScR guidelines. Eligible studies included observational studies reporting on patients younger than 50 years with gastrointestinal malignancies (esophageal, gastric, colorectal, hepatobiliary, pancreatic, or gallbladder cancers) in Nepal, while secondary data articles and case reports were excluded. Databases searched included PubMed, NepJol, and relevant grey literature. Reference lists of included articles were also screened. After duplicate removal, titles and abstracts were independently screened by two reviewers, followed by full-text review. Data were synthesized descriptively in narrative formats. Results: A total of 17 hospital-based studies from Nepal were included among 39 records. The colorectal cancer burden was increasing among young adults, with approximately 28% of cases in patients ≤40 years (mean age 31.8-34.1 years). Gastric cancer predominantly affected older adults (mean age 57-63 years), yet 10-22% were under 50. Early-onset gastric cancer cases showed a female predominance and often presented at an advanced stage. Esophageal cancer was most frequent in patients aged 61-70 years (34%); however, 20% were diagnosed before 50 years. Hepatocellular carcinoma affected mainly middle-aged to older adults (mean ages 54-67 years), with 8-26% of cases in younger individuals. Linked risk factors included male sex, viral hepatitis, alcohol use, and cirrhosis; late-stage diagnosis was common. Gallbladder and biliary tract cancers presented in middle-aged adults (mean age 53-56 years), typically presenting at advanced stages, with associated risk factors including gallstones, high parity, early menarche, Terai/Madhesi and Janajati ethnicity, alcohol and pesticide exposure, and low fruit/vegetable intake. Conclusions: Early-onset gastrointestinal cancers in Nepal constitute a significant proportion of the cancer burden, particularly for colorectal and gastric cancers, with younger patients often presenting with distinct clinical features. However, the scarcity of population-based data, national screening programs, and large cohort studies highlights critical knowledge gaps that must be addressed to inform early detection strategies, risk stratification, and targeted interventions in this population. Citation Format: Saroj GC, Bishal Paudel. Epidemiology of early-onset gastrointestinal cancers in Nepal: A scoping review [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-","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":"145717343","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 B010: Building a global research nextwork focusing on etiology for early-onset colorectal cancer (EOCRC): findings from the Fight Colorectal Cancer 2025 Barcelona Think Tank","authors":"Andrea J. Dwyer, Jose Perea, Daniel Buchanan, Rebecca Siegel, Kiran Ilgan, Anjee Q. Davis, Andrew Chan","doi":"10.1158/1557-3265.earlyonsetca25-b010","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b010","url":null,"abstract":"The rising incidence of early-onset colorectal cancer (EOCRC), which affects individuals under 50, is becoming a significant public health issue, particularly in high- and middle-income countries but now increase in lower income countries. EOCRC often lacks traditional risk factors like family history or hereditary syndromes and is associated with more aggressive tumors, delayed diagnoses, and considerable psychosocial and financial burdens. Due to fragmented data and a lack of large-scale studies, progress in EOCRC research has been limited. In response, Fight Colorectal Cancer (Fight CRC) organized the first-ever Global Think Tank on EOCRC, held in Barcelona, Spain, in June 2025, with the aim of aggregating global data, identifying emerging risk factors, establishing international research collaborations, and creating a sustained, patient-centered scientific network. The Think Tank utilized a hybrid consensus-development model, incorporating epidemiologic synthesis, data analysis, and stakeholder engagement. The event brought together 71 delegates from 18 countries, representing various fields, including molecular biology, oncology, and patient advocacy. Prior to the meeting, global data was gathered through a 36-item patient survey, which garnered 516 responses from 21 countries, an epidemiologic review of EOCRC incidence and mortality, and expert roundtables discussing potential etiologic factors. The two-day meeting was structured to foster interdisciplinary collaboration, with Day 1 focusing on EOCRC epidemiology and patient integration, and Day 2 addressing emerging hypotheses and regional disparities. New, unpublished data revealed that only 15.2% of EOCRC patients were aware that colorectal cancer could occur before 50, while 42% experienced diagnostic delays, often due to clinicians dismissing symptoms based on age. Furthermore, the incidence of EOCRC is rising by 1.5-4.0% annually, with the highest rates observed in New Zealand, Chile, and Puerto Rico. Over 60% of EOCRC cases are located in the rectum or sigmoid colon, and there were no significant sex-based differences in incidence. Real-time consensus polling indicated strong agreement that low awareness is a major barrier to early detection, with 92% of participants in favor of increasing awareness, and 85% emphasizing the role of diet and processed foods as key environmental factors. Five workgroups were formed, focusing on scientific research, epidemiologic tools, biobanking, global sustainability and advocacy, and risk stratification and awareness. These groups have created a 24-month roadmap that includes launching cohort studies, developing a data-sharing platform, establishing biobanks in underrepresented regions, and aligning global advocacy efforts. The meeting concluded with a commitment to ongoing international collaboration, prioritizing patient voices and ensuring equity, diversity, and inclusion. The momentum generated by this meeting sets the stage for future collabora","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"38 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717382","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 A004: Paid Family Leave as a Cancer Prevention Strategy? The association of state paid family leave implementation with early-onset breast and endometrial cancer incidence","authors":"Erica J. Lee Argov, Mary Beth Terry, Wan Yang, Parisa Tehranifar","doi":"10.1158/1557-3265.earlyonsetca25-a004","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-a004","url":null,"abstract":"Introduction: Breastfeeding reduces later risk of hormone-sensitive cancers. In the US, longer breastfeeding durations are associated with higher socioeconomic status (SES). Paid Family Leave (PFL), implemented in California (CA) since 2004, increased breastfeeding initiation and duration. We assessed whether PFL implementation reduced early-onset (age 20-54) breast and endometrial cancer incidence and explored modification by SES. Methods: In a quasi-experimental comparative interrupted time-series approach using registry-level Surveillance, Epidemiology, and End Results (SEER) data, we assessed annual age-adjusted incidence rates (2000-2019) for early-onset first malignant breast (C50) and endometrial (C54.1) cancers for women of working and reproductive age after PFL (diagnosed age 20-54). We compared changes in trends for registries exposed to PFL (in CA) to changes in trends for registries not exposed to PFL for areas with comparable pre-PFL trends. To account for cancer’s induction period, two lags (5 and 10 years) were evaluated, with the 5-year lag considered a negative control. We examined trends by race/ethnicity, and for breast cancer, by age (pre-screening >40 vs. post-screening ≥40) and hormone receptor (HR) status. Using the same approach, we compared differences in county-level incidence across quartiles of a county-level SES index. Results: For early-onset breast cancer, 10 years after PFL implementation, non-significantly reduced incidence trends (lowered slopes) were observed in PFL-exposed registries compared to non-PFL exposed registries, with the strongest reductions for non-Hispanic Black women age 40-54. PFL was associated with significantly reduced incidence trends for women 40-54 for counties in lower SES quartiles exposed to PFL compared to lower-SES counties not exposed to PFL (e.g., ∼7 fewer annual cases per 100,000 accounting for baseline trends in the lowest SES quartile). No difference was observed comparing counties in the highest SES quartile. For early-onset endometrial cancer, incidence trends were significantly lower for non-Hispanic American Indian /Alaska Native and Asian Pacific Islander women (2.8 and 2.1 fewer annual cases per 100,000, respectively) for PFL-exposed registries compared to unexposed registries. When examining county-level trends by SES, no significant differences in trends associated with PFL were observed within any SES quartile. Using the 5-year lag, no clear or consistent associations were observed for any cancer, race/ethnicity, or SES quartile. Conclusions: In this ecological analysis, reductions in early-onset breast and endometrial cancer incidence trends emerged 10 years after PFL implementation in CA among specific race-ethnicities. For early-onset breast cancer, associations were stronger among lower SES counties and not observed among high-SES counties. This supports the hypothesis that PFL may contribute to cancer prevention through mechanisms such as increased breastfeedi","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":"145717417","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 C006: Association of high birth weight with risk of early-onset colorectal cancer","authors":"Chun R. Chao, Lanfang Xu, Amrita Mukherjee, Darios Getahun, Jessica Chubak, Jane C. Figueiredo, Kimberly L. Cannavale, Alec Gilfillan, Bechien Wu","doi":"10.1158/1557-3265.earlyonsetca25-c006","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-c006","url":null,"abstract":"Introduction: The incidence of early-onset colorectal cancer (eoCRC) diagnosed under age 50 years has been increasing. The causes of this trend could be multifactorial and remain to be understood. The average birth weight has been increasing in the US since 1950. Intrauterine conditions can affect health outcomes later in life. Prior studies showed a link between high birth weight and risk of certain cancers in adolescent and young adults. Here we evaluated the hypothesis that high birth weight increases risk of eoCRC in a nested case-control study. Methods: We included patients diagnosed with colorectal adenocarcinoma at age 15-49 years at Kaiser Permanente Southern California (KPSC) (2009-2021). Cancer-free controls were matched at 10:1 ratio on age, sex, and length of prior KPSC membership using incidence density sampling. Study data were collected from KPSC’s electronic health records and birth data from California Department of Public Health. Record linkage with birth certificates from 1960 to 2005 was performed using date of birth, sex, and first, last, middle, and maiden names. Conditional logistic regression was used to estimate the association between eoCRC and high birth weight, measured using (1) neonatal macrosomia (birth weight > 4,000 grams), (2) large for gestational age (LGA; defined as birth weight > 90th percentile for gestational age and sex, using population references at KPSC), and (3) LGA stratified by sex and race/ethnicity. Analyses were repeated for colon and rectal cancer. Potential confounders or intermediates were assessed in crude models using threshold p-value <0.10. Two-stage model adjustments were performed: adjusting for race/ethnicity only, then additionally adjusting for obesity and hypertension (both had crude p-value <0.10). Results: Of 1,400 eligible eoCRC cases and 13,608 matched controls, 486 cases and 4,706 controls had linked birth certificate data (35% linked in both groups). After excluding cases without controls and vice versa, 471 cases (mean diagnosis age: 41.1 years) and 1,931 controls were included in the analysis. Of the 471 cases, 64% were male; 40% were non-Hispanic white; 64% had colon cancer, 36% had rectal cancer; and 12% had neonatal macrosomia. Both stages of models yielded similar results. In the fully adjusted model, high birth weight was associated with an elevated risk of overall eoCRC with marginal significance [odds ratio (OR)= 1.31 (95% CI: 0.94-1.82), 1.39 (0.96-2.02), and 1.38 (0.98-1.95) for neonatal macrosomia, LGA, and LGA stratified by sex and race/ethnicity, respectively]. Neonatal macrosomia and LGA were significantly associated with rectal cancer [OR= 1.80 (1.03-3.14) and 1.90 (1.04-3.48), respectively], but not with colon cancer [OR= 1.13 (0.75-1.71) and 1.17 (0.73-1.86), respectively]. Conclusions: We observed an association between high birth weight and risk of early-onset rectal cancer independent of adult metabolic abnormality, which should b","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"26 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717308","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}