Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology最新文献

{"title":"Integrating In Situ Immune Expression Landscape with Gene Expression-Based Subtyping to Characterize Breast Cancer Heterogeneity.","authors":"Mustapha Abubakar, Hela Koka, Priscilla Ming Yi Lee, Hiu Yu Natalie Tang, Scott Lawrence, Karun Mutreja, Feng Wang, Cherry Wu, Koon-Ho Tsang, Yee-Kei Tsoi, W C Chan, Sze Hong Law, Ray Ka Wai Hung, Gary M K Tse, Kristine Jones, Aurelie Vogt, Maria Brown, Belynda D Hicks, Difei Wang, Bin Zhu, Lap Ah Tse, Xiaohong R Yang","doi":"10.1158/1055-9965.EPI-25-2068","DOIUrl":"10.1158/1055-9965.EPI-25-2068","url":null,"abstract":"<p><strong>Background: </strong>We previously identified three clinically relevant immune [i.e., low-tumor-infiltrating lymphocyte (TIL), high-TIL, and high-interferon-stimulated gene (ISG)] subtypes of luminal breast cancer using RNA sequencing in a cohort of women from Hong Kong. In this study, we evaluated whether standard, in situ immunohistochemistry (IHC), a more clinically accessible approach, could capture similar immune heterogeneity across intrinsic (PAM50) subtypes.</p><p><strong>Methods: </strong>In 148 patients with invasive breast cancer, we performed dual IHC staining for eight markers (CD3, CD8, CD20, FOXP3, CD68, CD163, PDL1, and IDO1) with pan-cytokeratin and quantified immune-positive cells in stromal regions by digital image analysis.</p><p><strong>Results: </strong>IHC marker expression strongly correlated with gene expression-based immune and intrinsic subtypes. Compared with luminal tumors classified as low-TIL, high-TIL tumors showed higher levels of CD3, CD8, CD20, PDL1, and IDO1. Similarly, high-ISG tumors expressed higher CD3, CD8, CD20, PDL1, and IDO1 than low-TIL tumors but were distinguished from high-TIL tumors by elevated CD163. Immune marker expression was generally higher in HER2-enriched and basal-like tumors than in luminal A and B tumors, though substantial variability existed within each subtype. Luminal B tumors expressed higher levels of CD3, CD8, CD20, and CD163 compared with luminal A tumors. Notably, immune infiltration was more strongly aligned with aggressive tumor features such as high grade, risk of recurrence scores, and TP53 mutations than with estrogen receptor/progesterone receptor expression.</p><p><strong>Conclusions: </strong>These findings confirm that subsets of luminal tumors harbor inflamed or macrophage-driven immune microenvironments.</p><p><strong>Impact: </strong>Parsimonious IHC panels can perform immune classification, supporting their potential utility in refining subtype stratification and informing clinical decision-making, particularly in resource-limited settings.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1358-1367"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Muscle Density Is Associated with Morbidity and Systemic Inflammation in Colorectal Cancer, Independent of Tumor Factors.","authors":"Raila Aro, Sanna Meriläinen, Juha P Väyrynen, Juha Saarnio, Päivi Sirniö, Ville K Äijälä, Vilja V Tapiainen, Henna Karjalainen, Meeri Kastinen, Reetta Häivälä, Jukka Rintala, Tero Rautio, Taina Tervahartiala, Timo Sorsa, Markus J Mäkinen, Anne Tuomisto","doi":"10.1158/1055-9965.EPI-26-0189","DOIUrl":"10.1158/1055-9965.EPI-26-0189","url":null,"abstract":"<p><strong>Background: </strong>Low skeletal muscle index (SMI) and skeletal muscle density (SMD) are associated with poor postoperative outcomes in colorectal cancer. However, standardized diagnostic thresholds remain undefined.</p><p><strong>Methods: </strong>In total, 927 patients with stage I to IV colorectal cancer were included. Preoperative computed tomography was used to determine body composition parameters. Optimal stratification was applied to identify the sex-specific and body mass index (BMI)-specific SMD and SMI cutoffs. SMD and SMI were analyzed as continuous variables relative to clinicopathologic features, systemic inflammatory markers, and sex-specific quartiles in survival analyses using Kaplan-Meier and Cox regression methods.</p><p><strong>Results: </strong>Optimal stratification did not yield reproducible cutoff values for SMI or SMD. In multivariable analysis, low SMD and SMI were associated with female sex, older age, and BMI, whereas tumor-related factors were not associated with either measure. Low SMD was associated with systemic inflammation, including elevated circulating C-reactive protein and interleukin 6 (IL6) levels, whereas low SMI showed only a nominal association with elevated IL6 levels after adjustment. Low SMD independently predicted poorer cancer-specific survival [multivariable hazard ratio (HR) for lowest vs. highest SMD = 4.29; 95% confidence interval (CI), 1.86-9.91; P = 0.001] and overall survival (HR for lowest vs. highest SMD = 3.42; 95% CI, 1.62-7.25; P = 0.003) in women but not in men, whereas SMI was not associated with survival.</p><p><strong>Conclusions: </strong>Low SMD is a sex-specific prognostic factor. Incorporating SMD assessment into preoperative risk stratification may enhance individualized management, particularly for female patients.</p><p><strong>Impact: </strong>Survival-based cutoff values for SMD or SMI in colorectal cancer could not be established. Moreover, preoperative body composition reflects patient-related factors rather than tumor-induced changes.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1289-1297"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Disease and Breast Cancer Risk in the Sister Study.","authors":"Jennifer M P Woo, Dazhe Chen, Rina Yarosh, Katie M O'Brien, Dale P Sandler","doi":"10.1158/1055-9965.EPI-25-1499","DOIUrl":"10.1158/1055-9965.EPI-25-1499","url":null,"abstract":"<p><strong>Background: </strong>Thyroid disease and its treatments are suspected risk factors for breast cancer, attributed primarily to alterations in thyroid hormone-related metabolism. Prior literature is inconsistent, in part, due to small sample sizes. We, therefore, assessed the effects of hyper- and hypothyroidism on incident breast cancer in a large cohort of US women.</p><p><strong>Methods: </strong>Data are from the Sister Study, a prospective cohort of 50,884 US women with no breast cancer history at enrollment (2003-2009; ages 35-74 years) and follow-up through September 2021. We used time-varying Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between self-reported thyroid diseases and treatments and incident breast cancer.</p><p><strong>Results: </strong>Of 45,783 eligible participants, 11,567 reported thyroid disease at baseline and over follow-up (hyperthyroidism: n = 1,710; hypothyroidism: n = 9,857), and 3,897 participants subsequently developed breast cancer. Breast cancer HR was 1.15 (95% CI, 0.95-1.39) for those with hyperthyroidism and 0.93 (95% CI, 0.85-1.01) for those with hypothyroidism, compared with no thyroid disease, with similar patterns observed across racial and ethnic groups. Hyperthyroidism was associated with greater premenopausal breast cancer hazard (HR = 1.85; 95% CI, 1.11-3.07) and differed from breast cancer hazard for hypothyroidism, which seemed reduced (HR = 0.75; 95% CI, 0.54-1.05) but did not reach statistical significance (Pheterogeneity = 0.06). Breast cancer hazards were higher, albeit not statistically significant, for those treated for hyperthyroidism but not hypothyroidism.</p><p><strong>Conclusions: </strong>Women diagnosed with hyperthyroidism or receiving related treatment may have an elevated breast cancer risk, particularly for premenopausal breast cancer.</p><p><strong>Impact: </strong>Although more research is needed, premenopausal women treated for hyperthyroidism may benefit from enhanced breast cancer screening.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1368-1374"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAX1 and ZNF582 Methylation as a Triage Strategy in Cytologic and hrHPV+ Scrapings in Both Chinese and Dutch Cohorts.","authors":"Na Li, Yuanjing Hu, Ate G J van der Zee, Ed Schuuring, G Bea A Wisman","doi":"10.1158/1055-9965.EPI-26-0015","DOIUrl":"10.1158/1055-9965.EPI-26-0015","url":null,"abstract":"<p><strong>Background: </strong>The methylation of paired boxed gene 1 (PAX1) and zinc finger protein 582 (ZNF582) has been proved to have good diagnostic efficacy to detect cervical precancerous lesions in Asian populations, but their performance in Dutch populations is still unclear. We assessed PAX1 and ZNF582 methylation in both Dutch and Chinese cohorts.</p><p><strong>Methods: </strong>Cervical scrapings were evaluated from 2 independent groups. The Dutch cohort (population-based screening) provided 190 abnormal cytology scrapings, and 138 cases tested positive for high-risk human papillomavirus (hrHPV). The hospital-based Chinese cohort included 246 specimens (205 abnormal cytology and 227 hrHPV+). Quantitative methylation-specific PCR was employed to analyze methylation.</p><p><strong>Results: </strong>PAX1 and ZNF582 methylation showed high specificity of 91% to 97% with moderate sensitivity of 43% to 61% for cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+) in abnormal cytology and hrHPV+ samples in both cohorts. Sensitivity for CIN3+ increased to 55% to 86% but with lower specificity (85%-93%). For detecting CIN2+, PAX1/ZNF582 methylation performed similarly in Dutch and Chinese cohorts. However, for CIN3+, the Chinese cohort showed significantly higher sensitivity, with comparable specificity. We also evaluated combining these genes with our established markers (C13ORF18, JAM3, and ZSCAN1). The best diagnostic performance was achieved by combining PAX1 or ZNF582 with JAM3 in the Dutch cohort.</p><p><strong>Conclusions: </strong>In conclusion, regardless of race or geography, methylation of PAX1 or ZNF582 is highly specific for detecting CIN2+/CIN3+ lesions in hrHPV+ or cytologically abnormal scrapings. Triage testing using these markers might significantly reduce immediate colposcopies.</p><p><strong>Impact: </strong>PAX1/ZNF582 methylation triage for cytology+/hrHPV+ scrapings may reduce immediate colposcopies.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1411-1420"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive Predictive Value of Symptoms for Early-Onset Colorectal Cancer.","authors":"Jessica Chubak, Laura Ichikawa, Rebecca A Ziebell, Natalia Udaltsova, Douglas A Corley, Nirupa R Ghai, Jeffrey K Lee, Ethan A Halm, Celette Sugg Skinner, Charles Quesenberry, Joanne E Schottinger, Theodore R Levin","doi":"10.1158/1055-9965.EPI-25-0697","DOIUrl":"10.1158/1055-9965.EPI-25-0697","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing colorectal cancer in people below age 50 relies largely on the evaluation of symptoms despite recent recommendations to initiate screening at age 45. There is limited information on the positive predictive value (PPV) of symptoms as indicators of early-onset colorectal cancer.</p><p><strong>Methods: </strong>We identified patients aged 42 to 49 years in three community-based health systems between 2012 and 2020 whose first recorded colonoscopy had a diagnostic indication, with symptoms present in the two years before the colonoscopy. We computed the PPV for colorectal cancer by each individual symptom, combinations of the three most common symptoms, and combinations of the three symptoms with the highest PPVs and computed 95% confidence intervals (CI). We also evaluated the PPV of recent symptoms stratified according to the timing of onset and estimated the PPV of symptoms when followed by positive or negative fecal testing.</p><p><strong>Results: </strong>The study included 28,198 patients. The PPV for specific symptoms, with or without other symptoms, was 2.4% (95% CI, 2.2%-2.7%) for blood loss and 4.5% (95% CI, 3.3%-5.9%) for positive fecal testing. Pairwise and three-way combinations of blood loss, diarrhea, and abdominal mass had PPV point estimates for colorectal cancer above 3%.</p><p><strong>Conclusions: </strong>Our study suggests that specific symptoms and combinations may identify patients with a ≥3% prevalence of colorectal cancer in those aged 42 to 49 and that fecal testing results may further identify patients with a higher probability of colorectal cancer.</p><p><strong>Impact: </strong>Future research is needed to develop high PPV strategies for identifying early-onset colorectal cancer without compromising sensitivity. See related In the Spotlight, p. 1233.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1276-1282"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13047898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary and Lifestyle Patterns among Young Patients with Lung Cancer: Analysis of Mutation-Specific Phenotypes.","authors":"Sarah D Gorbatov, Marisa A Bittoni, Anna H Wu, Allison Harper, Virginia Kotait, Narjust Florez, David P Carbone, Barbara Gitlitz, Jorge Nieva","doi":"10.1158/1055-9965.EPI-26-0057","DOIUrl":"10.1158/1055-9965.EPI-26-0057","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer in young adults is biologically distinct, with 84% harboring targetable mutations largely unassociated with active and passive tobacco exposure. Environmental risk factors remain poorly characterized in this predominantly female, non-tobacco smoking population.</p><p><strong>Methods: </strong>We analyzed 187 patients in the Epidemiology of Young Lung Cancer study using biological pathway groupings: EGFR Pathway (EGFR + ERBB2), Fusion-Positive (ALK + ROS1 + RET + NTRK), and Other/Mixed Mutations (KRAS, BRAF, MET exon 14 skipping, TP53, and additional alterations). Dietary quality was assessed using the Healthy Eating Index (HEI)-2015 and compared with US reference values from National Health and Nutrition Examination Survey. Statistical comparisons used one-sample t tests.</p><p><strong>Results: </strong>Active and passive tobacco use diverged from traditional mutation associations. In the Other/Mixed Mutations group, 68.8% never used tobacco despite these mutations being linked to tobacco exposure. Conversely, the EGFR Pathway group included 32.9% with a history of tobacco use. Oral contraceptive use among females was consistently elevated (81.7%-90.2%). Dietary analysis revealed that EGFR Pathway and Fusion-Positive patients demonstrated higher HEI-2015 scores versus the US reference (64.9 ± 10.7 and 65.5 ± 9.8 vs. 58) and consumed more total vegetables (4.2 vs. 3.5), fruits (3.3 vs. 2.5), and whole grains (3.9 vs. 2.6).</p><p><strong>Conclusions: </strong>Young patients with lung cancer demonstrated mutation-specific environmental exposure patterns distinct from older populations. EGFR Pathway and Fusion-Positive patients had the highest diet quality scores, driven primarily by higher intake of vegetables, fruits, and whole grains-food categories with established protective associations and documented pesticide residues.</p><p><strong>Impact: </strong>These findings highlight nontobacco environmental exposures in young patients with lung cancer and support further investigation of dietary patterns and hormonal factors in mutation-specific disease pathways.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1453-1462"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13340576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper Promotes Breast Cancer through Immunometabolic Reprogramming: A Multi-omics Mediation Analysis.","authors":"Na Wang, Chen Suo, Yan Wu, Jing Zheng, Baokun Cao, Ziyu Yuan, Weimin Ye, Haomin Yang, Xingdong Chen","doi":"10.1158/1055-9965.EPI-26-0172","DOIUrl":"10.1158/1055-9965.EPI-26-0172","url":null,"abstract":"<p><strong>Background: </strong>Elevated copper (Cu) concentration or copper to zinc (Cu/Zn) ratio have been consistently observed in the blood and tumor tissues of patients with breast cancer, although the underlying mechanisms remain unclear. The objective of this study was to assess the effects of plasma Cu on breast cancer risk and the associated immunometabolic pathways.</p><p><strong>Methods: </strong>We conducted a nested case-control study (226 matched pairs) within the Taizhou Longitudinal Study. Plasma levels of Cu and Zn were quantified, and large-scale proteomic and metabolomic profiling was performed. Structural equation modeling and network toxicology analyses were applied to explore Cu-associated immunometabolic pathways.</p><p><strong>Results: </strong>Higher plasma Cu was significantly associated with increased breast cancer risk (adjusted OR = 1.29; 95% CI, 1.04-1.61). Proteomic analyses identified two Cu-related inflammatory proteins, CCL23 and HGF, significantly linked to breast cancer. The metabolites associated with breast cancer, HGF and CCL23, were enriched in alanine, aspartate, and glutamate metabolism. Structural equation modeling revealed two Cu-driven immunometabolic axes: (i) Cu→CCL23→succinate/NAAG and (ii) Cu→HGF→NAAG, mediating approximately 30% of Cu's effect on breast cancer risk. Functional enrichment of succinate-related genes implicated apoptosis, mitochondrial regulation, and MAPK/JAK-STAT signaling. NAAG-related genes were enriched in proteolytic activity, focal adhesion, and actin cytoskeleton remodeling pathways, indicating roles in tumor progression.</p><p><strong>Conclusions: </strong>Our findings reveal novel Cu-driven immunometabolic pathways mediating breast cancer risk through inflammation-metabolism cross-talk. These insights highlight potential targets for prevention and intervention in Cu-associated breast carcinogenesis.</p><p><strong>Impact: </strong>Findings in this study highlight potential targets for prevention and intervention in Cu-associated breast carcinogenesis.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1392-1401"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148059270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interval from Cancer Diagnosis to Depression Onset and Risk of Dementia in Cancer Survivors.","authors":"Sangjun Lee, Soyeoun Kim","doi":"10.1158/1055-9965.EPI-26-0336","DOIUrl":"10.1158/1055-9965.EPI-26-0336","url":null,"abstract":"<p><strong>Background: </strong>The primary aim of our study is to examine how the timing of depression after cancer diagnosis relates to the risk of all-cause dementia (ACD) and Alzheimer disease (AD) and to compare time-fixed and time-varying modeling approaches.</p><p><strong>Methods: </strong>We conducted a nationwide cohort study using Korean National Health Insurance Service data on 385,092 individuals aged ≥55 years diagnosed with cancer between 2009 and 2013, with no dementia or depression, followed through 2023. Depression was identified using International Classification of Diseases, Tenth Revision, codes F32 to F33 and categorized by the interval from cancer diagnosis. Depression was modeled as a baseline time-fixed or a time-varying exposure. The primary outcome was ACD, and the secondary outcome was AD. Cox proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CI), adjusting for demographic, lifestyle, and cardiometabolic factors.</p><p><strong>Results: </strong>Over a median follow-up of 11.7 years, 71,600 participants (18.6%) developed ACD. Time-fixed models suggested an increased dementia risk for depression diagnosed within 5 years after cancer but an apparent inverse association for depression diagnosed >5 years after cancer (aHR, 0.90; 95% CI, 0.87-0.93). In contrast, time-varying models showed consistently elevated risks across all depression-onset intervals, including >5 years after cancer (aHR, 2.09; 95% CI, 2.02-2.17). Results were similar for AD.</p><p><strong>Conclusions: </strong>Depression at any time after cancer diagnosis is associated with increased dementia risk when modeled. Time-fixed analyses may introduce immortal time bias and mischaracterize risk, underscoring the importance of time-varying approaches in survivorship research.</p><p><strong>Impact: </strong>Modeling postcancer depression as a time-varying exposure clarifies dementia risk estimates and informs survivorship mental health strategies.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1329-1336"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Composite Low-Grade Inflammation Score and Cancer Outcomes: Results from the Moli-sani Study.","authors":"Simona Costanzo, Augusto Di Castelnuovo, Marialaura Bonaccio, Sara Magnacca, Teresa Panzera, Amalia De Curtis, Francesca Bracone, Giulia Martinelli, Roberta Parisi, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello","doi":"10.1158/1055-9965.EPI-26-0312","DOIUrl":"10.1158/1055-9965.EPI-26-0312","url":null,"abstract":"<p><strong>Background: </strong>Epidemiologic evidence links low-grade inflammation to an increased risk of chronic degenerative diseases, but its relationship with cancer remains controversial. This study aimed to investigate the association between a composite low-grade inflammation score and different cancer outcomes on a large epidemiologic scale.</p><p><strong>Methods: </strong>A prospective analysis was conducted among 18,933 individuals (51.8% women; age ≥35 years) free of cancer, chronic inflammation, or hematologic diseases from the Moli-sani cohort. Low-grade inflammation was assessed using the INFLA-score, derived from C-reactive protein, granulocyte-to-lymphocyte ratio, and leukocyte and platelet counts. Hazard ratios (HR) and 95% confidence intervals (CI) for cancer mortality, cancer-related hospitalization, and colorectal cancer were estimated across INFLA-score fifths using multivariable Cox proportional hazard models.</p><p><strong>Results: </strong>During a 13.1-year follow-up, 612 cancer deaths, 1,854 cancer-related hospitalizations, and 287 colorectal cancer cases were ascertained. Individuals in the highest INFLA-score fifth showed higher hazard of cancer mortality (HRQ5vsQ1-Q4: 1.19; 95% CI, 0.99-1.44), cancer-related hospitalization (1.21; 1.08-1.34), and colorectal cancer (1.68; 1.30-2.18), compared with lowest fifths, independently of health-related behaviors and chronic diseases. Associations were more pronounced for cancer mortality and hospitalization in older individuals and those with a cancer family history and for colorectal cancer among women (all P for interaction >0.05). Increased cancer mortality hazard was observed among normal-weight and overweight individuals but not in obese individuals (P for interaction = 0.039).</p><p><strong>Conclusions: </strong>Higher INFLA-score is associated with increased hazard of cancer hospitalization and colorectal cancer.</p><p><strong>Impact: </strong>Subclinical inflammation may be a prognostic indicator for cancer, underscoring the potential role of lifestyle interventions and systemic inflammation monitoring in cancer prevention.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":"1402-1410"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147978617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Importance of Minority Stress and Intersectionality for Cancer Symptom Management: The Case of Cancer-Related Pain.","authors":"Milena E Insalaco, Oscar Y Franco-Rocha, Laura Stamm, Nikesha Gilmore, Charles Kamen","doi":"10.1158/1055-9965.EPI-26-0496","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-26-0496","url":null,"abstract":"<p><p>Although research demonstrates that cancer survivors who are sexual and gender minorities (SGM), racial and ethnic minorities, or of lower socioeconomic status experience a higher prevalence of cancer-related pain, limited studies have examined how these intersecting marginalized identities and additional social experiences interconnect and affect pain outcomes. In their recent study, Boehmer and colleagues conducted an intersectional analysis of cancer-related pain among SGM adults and other marginalized backgrounds. Using data from the Behavioral Risk Factor Surveillance System, they found that SGM individuals reported a higher prevalence of cancer-related pain. SGM adults with a history of cancer who were younger than 65 years, Black or Hispanic, had low income, unemployed, never or formerly married, and reported poor access to care demonstrated higher likelihood of pain prevalence than their heterosexual cisgender counterparts. In this commentary, we explore minority stress, defined as the socially based and chronic stress associated with stigma, fear of discrimination, and prejudice, as a possible contributing factor to this higher prevalence of pain among those with intersecting marginalized identities, through its effect on biological function and symptoms. The findings of Boehmer and colleagues' study underscore the need to further explore intersectional approaches to pain management in cancer care and research. See related article by Boehmer et al., p. 1309.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":"35 8","pages":"1236-1238"},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}