International Journal of Cancer最新文献

{"title":"A mass cytometry-based lens on DNA damage repair in circulating tumor cells from breast cancer patients.","authors":"Aleksandra Markiewicz","doi":"10.1002/ijc.70105","DOIUrl":"https://doi.org/10.1002/ijc.70105","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen escape in CAR-T therapy: A tumor microenvironment perspective from hematological to solid tumors.","authors":"Shuai Wang, Wenying Li, Jiayi Li, Zhigang Guo, Jiannan Chen, Zhigang Hu","doi":"10.1002/ijc.70117","DOIUrl":"https://doi.org/10.1002/ijc.70117","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in hematologic malignancies, but antigen escape remains a major challenge, especially in solid tumors, where the tumor microenvironment (TME) exacerbates the problem. Mechanisms of antigen escape include antigen loss, epitope masking, lineage switching, and trogocytosis-mediated CAR dysfunction. The TME promotes immune evasion through physical barriers, immunosuppressive cells, and metabolic competition. To overcome these challenges, multi-targeted CAR-Ts, gene editing, epigenetic interventions, and combination therapies have been developed to enhance CAR-T efficacy. Emerging strategies-such as microbial-guided antigen labeling, nanotechnology for metabolic normalization, armored CAR-T secreting TME-modulating agents, and adaptive CAR systems responsive to TME signals-offer new solutions to target \"cold\" tumors. Future breakthroughs will rely on synergizing dynamic CAR systems for broad antigen coverage, achieved via multi-targeting and non-canonical antigen recognition, with engineered TME remodeling driven by microbial, viral, and immune cell allies, as well as armored CAR-T cells secreting immunomodulators. Combined with metabolic engineering and interdisciplinary innovation, this integrated approach will effectively enable CAR-T cells to orchestrate a multi-faceted anti-tumor ecosystem rather than functioning in isolation.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential HPV16 variant infections in the genital epithelium and anal canal of men.","authors":"Racheal S Dube Mandishora, Milena Giulia Gonçalves, Wenyi Fan, Bradley Sirak, Matthew Thomas Ferreira, Richard R Reich, Kimberly Isaacs-Soriano, Martha Abrahamsen, Eduardo Lazcano Ponce, Luisa L Villa, Anna R Giuliano, Laura Sichero","doi":"10.1002/ijc.70111","DOIUrl":"https://doi.org/10.1002/ijc.70111","url":null,"abstract":"<p><p>This study aimed to assess HPV16 variant period prevalence and sequential acquisition at genital and anal sites in men from the USA and Latin America, using data from the HPV Infection in Men (HIM) Study cohort. Among 635 men with genital and 115 with anal HPV16, 53 men tested positive for any HPV16 variant at both sites, and HPV16 A1 was most prevalent at both sites, more so at the anal canal. Sequential acquisition of HPV16 A1 occurred in 30.4% (genital to anal) and 29.4% (anal to genital). These findings offer insight into HPV16 variant distribution across anatomic sites in men.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating fatty acid binding protein 4 (FABP-4) concentrations and mortality in individuals with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.","authors":"Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon","doi":"10.1002/ijc.70090","DOIUrl":"https://doi.org/10.1002/ijc.70090","url":null,"abstract":"<p><p>Human fatty acid binding protein-4 (FABP-4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity-mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC-specific, non-CRC-specific, and all-cause mortality by FABP-4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC and non-CRC deaths. Mediation analyses were conducted to estimate total effects (TEs), direct effects (DEs), and mediation proportions (MPs) by FABP-4 of pre-diagnostic body mass index (BMI) on mortality. In the fully adjusted model including BMI, higher circulating FABP-4 concentrations were associated with higher CRC mortality (HR_Q4vsQ1 = 1.49; 95% CI: 1.11-2.00) and all-cause mortality (HR_Q4vsQ1 = 1.49; 95% CI: 1.15-1.93), but not statistically associated with non-CRC mortality (HR_Q4vsQ1 = 1.51; 95% CI: 0.82-2.76). The TE and DE per 5 kg/m² of BMI on all-cause mortality were 1.21; 95% CI: 1.10-1.34, and 1.13; 95% CI: 1.02-1.26, respectively, with a MP of 34.5% (p = .002) by FABP-4. For CRC-specific and non-CRC-specific mortality, MPs by FABP-4 were 33.7% (p = .03) and 36.1% (p = .02), respectively. In conclusion, higher concentrations of FABP-4 were associated with higher CRC-specific and all-cause mortality in individuals with CRC. FABP-4 was a significant partial mediator of the adiposity-mortality relationship in individuals with CRC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline variants observed in pediatric cancer patients related to hereditary breast and ovarian cancer in adults.","authors":"Katharina Daugs, Danielle Brandes, Layal Yasin, Ammarah Anwar, Jubayer Alam, Yash Prasad, Jil Bartrina Y Manns, Melina Mescher, Ute Fischer, Arndt Borkhardt, Triantafyllia Brozou, Stefanie V Junk","doi":"10.1002/ijc.70097","DOIUrl":"https://doi.org/10.1002/ijc.70097","url":null,"abstract":"<p><p>Genetic predisposition is a major cause of cancer, yet little is known about the role of adult cancer predisposition syndromes (CPSs) in childhood cancers. Although extensively studied in adults, information about the impact of germline variants in genes associated with hereditary breast and ovarian cancer (HBOC) remains scarce in the pediatric context. To elucidate whether (likely) pathogenic variants (LP/PVs) in 25 selected HBOC-related genes may contribute to cancer risk in children, we analyzed the spectrum of occurring germline variants. We assessed 372 children (median age at diagnosis 5.1 [0-22.2] years; 160 girls [43%]), including 212 (57%) with hematologic neoplasms, 71 (19%) with brain tumors, and 89 (24%) with various solid entities. Twenty-seven of 372 patients (7%) carried LP/PVs in the candidate genes; for 12 of 27 (44%) no CPS was suspected prior to genotyping. LP/PV carriers were particularly at risk for second malignancies (SMN; 5/27 vs. 13/345; OR = 5.8; p = .0021); yet, LP/PVs in SMN-developing patients resided exclusively in TP53 (n = 3), NBN (n = 1), and ATM (n = 1). Burden testing of our single-center cohort revealed considerable associations between monoallelic LP/PVs in five HBOC-related genes (TP53, CHEK2, ATM, NF1, and NBN) and pediatric cancers compared to healthy adults (gnomAD v.3.1.1, non-cancer dataset). Joint analyses adding 1120 individuals from a previous study Zhang et al. (2015) confirmed significant associations for TP53, CHEK2, NF1, and MSH2. Monoallelic LP/PVs in constrained HBOC-related genes are significantly associated with pediatric cancers. However, particularly in clinically unexpected cases, detection of contributing LP/PVs by genotype-driven approaches may improve patient outcomes by enabling risk-adapted therapy and surveillance.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative omics approaches to uncover liquid-based cancer-predicting biomarkers in Lynch syndrome.","authors":"Minta Kärkkäinen, Tero Sievänen, Tia-Marje Korhonen, Joonas Tuomikoski, Kirsi Pylvänäinen, Sami Äyrämö, Toni T Seppälä, Jukka-Pekka Mecklin, Eija K Laakkonen, Tiina Jokela","doi":"10.1002/ijc.70106","DOIUrl":"https://doi.org/10.1002/ijc.70106","url":null,"abstract":"<p><p>Lynch syndrome is a genetic cancer-predisposing syndrome caused by pathogenic mutations in DNA mismatch repair (path_MMR) genes. Due to the elevated cancer risk, novel screening methods, alongside current surveillance techniques, could enhance cancer risk stratification. Here we show how bi-omics integration could be utilized to pinpoint potential cancer-predicting biomarkers in Lynch syndrome. We studied which blood-based circulating microRNAs and metabolites could predict Lynch syndrome cancer occurrence within a 5.8-year prospective surveillance period. We used single- and bi-omics bioinformatic analyses and identified omics-level patterns and associations across these biological layers. Lasso Cox regression was used to highlight the most promising cancer-predicting biomarkers. Our findings revealed distinct circulating metabolite landscapes among path_MMR variant carriers and a circulating microRNA co-expression module significantly associated with future cancer incidence. These microRNAs regulate cancer-related pathways, including the PI3K/Akt signaling pathway. Additionally, a metabolite module consisting of ApoB-containing lipoproteins (low-, intermediate-, and very low-density lipoproteins) showed distinct levels across path_MMR variants. Notably, three biomarkers-hsa-miR-101-3p, hsa-miR-183-5p, and triglycerides in high-density lipoprotein particles (HDL_TG)-significantly predicted cancer risk, achieving a Harrel's Concordance Index (C-index) of 0.76 (p = .0007). Elevated levels of these biomarkers indicated increased cancer risk. Internal validation of the model yielded a C-index of 0.72. The bi-omics approach and the identified biomarkers offer promising insights for future studies regarding cancer risk identification in Lynch syndrome.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body height and the excess cancer risk in men.","authors":"Cecilia Radkiewicz, Gustaf Edgren, Arvid Sjölander, Emelie Benyi, Mats Lambe, Paul W Dickman, Lars Sävendahl","doi":"10.1002/ijc.70108","DOIUrl":"https://doi.org/10.1002/ijc.70108","url":null,"abstract":"<p><p>Men have a higher risk than women for most cancers affecting both sexes. Since taller stature is associated with increased cancer risk and men are, on average, taller than women, we investigated to what extent adult body height, as a proxy for stem cell number, explains the elevated cancer risk in men. This population-based cohort study linked adult height information from Swedish conscripts, mothers, and passports to the National Cancer and Cause of Death Registers (1960-2011). We used mediation survival analysis to estimate the proportion of the association between male sex and site-specific cancer risk mediated by adult height, our main outcome. Statistical significance was assessed using two-sided tests with a .05 significance level. Among 6,156,659 adults, we observed 285,778 non-sex-specific cancer cases. Male sex was significantly associated with cancer risk at 33 of 39 sites, and greater height with increased risk at 27 of 39 sites. Height mediated 0.5%-100% of the excess male cancer risk, with the highest proportions for salivary gland cancer, colon cancer, melanoma, and acute myeloid leukemia. The effects of height and its mediated effect were most consistent for malignancies with weak or no established environmental risk factors. These findings indicate that a substantial proportion of the excess cancer risk in men may be explained by height. This highlights the role of stochastic biological processes linked to height, as well as genetic and early-life determinants of height, in contributing to sex differences in cancer risk, beyond influences of adult lifestyle and environmental exposures.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal patterns of penile human papillomavirus detection among Ugandan men: A prospective sampling study.","authors":"Xinyi Feng, Eshan U Patel, Godfrey Kigozi, Patti E Gravitt, Ronald M Galiwango, Molly R Petersen, Fred Nalugoda, Andrew D Redd, Steven J Reynolds, Thomas C Quinn, M Kate Grabowski, Aaron A R Tobian","doi":"10.1002/ijc.70107","DOIUrl":"https://doi.org/10.1002/ijc.70107","url":null,"abstract":"<p><p>Human papillomavirus (HPV) is a highly prevalent sexually transmitted infection, yet data on HPV dynamics in African male populations remain limited. We conducted a prospective study of 300 human immunodeficiency virus-negative, sexually active Ugandan men enrolled at circumcision and followed every 6 weeks for 6 months. Penile swabs were collected by clinical staff, and HPV DNA was detected using the Roche polymerase chain reaction-based linear array assay at six time points. We estimated both point and cumulative prevalence of any and high-risk HPV, and assessed empirical and bootstrapped absolute and relative differences to quantify bias from relying solely on baseline testing. The baseline prevalence of any HPV was 49.7%, increasing to 66.0% when cumulative results were considered. Among 27 men with swabs with amplifiable viral or cellular DNA at all six visits, 100% tested positive at least once. HPV detection was often transient: only 6.1% of men with any HPV were consistently positive at all visits. Men who were ever HPV positive reported a younger age at first sex and more sexual partners. Single-timepoint testing significantly underestimated HPV prevalence, with relative biases of 24.7% for any HPV and 40.3% for high-risk HPV. Bootstrap analyses showed that reducing absolute bias to below 5% required two visits for any HPV and three for high-risk HPV, whereas achieving relative bias below 5% required three and five visits, respectively. The results remained consistent in sensitivity analyses that excluded pre-circumcision visits. These findings highlight the limitations of cross-sectional HPV testing and emphasize the importance of repeated sampling for accurate surveillance and vaccine impact assessments in male populations.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folic acid fortification and late-onset colorectal cancer risk: A systematic assessment of the worldwide evidence.","authors":"Tongtong Li, Yuan Li, Lina Yin, Wen Li, Zhenshu Li, Fei Ma, Yongjie Chen, Jing Yan, Guowei Huang","doi":"10.1002/ijc.70109","DOIUrl":"https://doi.org/10.1002/ijc.70109","url":null,"abstract":"<p><p>Concerns have been raised about potential hazards associated with folic acid fortification. This study aimed to explore associations between diverse folic acid fortification policies (mandatory vs. no mandatory fortification) and global late-onset colorectal cancer (LOCRC) incidence rates. The study systematically assessed (i) folic acid fortification policies in 193 member states of the World Health Organization, and (ii) age-standardized LOCRC incidence rates by country. We examined the associations between folic acid fortification types and LOCRC incidence using an ecological study design. Incidence trends before and after fortification were analyzed using a log-linear joinpoint regression model, and the annual percent change and average annual percent change with 95% confidence interval were determined for representative countries with mandatory fortification (the United States [U.S.] and Canada). By September 2024, 69 countries enacted mandatory folic acid fortification legislation, while 124 had no fortification. The overall LOCRC incidence rates per 100,000 were 70.8 and 84.0 with mandatory and no mandatory fortification, respectively. The decreasing trends after implementing folic acid fortification were more rapid than in the pre-fortification period in the U.S. and Canada. These findings suggested an association between mandatory folic acid fortification policies and reduced LOCRC incidence. These global data provide a scientific basis for transitioning fortification policies and inform strategies for cancer prevention through the fortification with folic acid.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cause-specific mortality after a diagnosis of ductal carcinoma in situ: Associations with screening and socio-economic status.","authors":"Renée S J M Schmitz, Alexandra W van den Belt-Dusebout, Maartje van Seijen, Ellen A J Verschuur, Frederieke H van Duijnhoven, Michael Schaapveld, Esther H Lips, Jelle Wesseling, Marjanka K Schmidt","doi":"10.1002/ijc.70112","DOIUrl":"https://doi.org/10.1002/ijc.70112","url":null,"abstract":"<p><p>The lower all-cause mortality in women with Ductal carcinoma in situ (DCIS) compared with the general population has been hypothesized to be due to a \"healthy-user effect,\" but this has not been studied in large cohorts. In a population-based, retrospective cohort study comprising 18,942 women with primary DCIS between 1999 and 2015 in the Netherlands, the cumulative incidence of breast cancer death (BCD) was estimated using death by other cause as a competing risk. The cause-specific mortality risk of women with DCIS was compared with that of the Dutch female population. Multivariable competing risk regression was used to quantify the effects of the method of detection and socio-economic status (SES). With 289 BCDs, the 10-year cumulative incidence of BCD was 1.3% (95% CI, 1.1-1.5). Compared to the Dutch female population, women with DCIS had a 2.1-times higher risk of BCD, but a 7% lower risk of all-cause mortality. Women with screen-detected DCIS had lower risks of BCD compared to women with non-screen-detected DCIS (subdistribution hazard ratio [sHR]:0.60, 95% CI 0.47-0.77), as did women with high SES versus low SES (sHR 0.54, 95% CI 0.30-0.97) in the first 4 years of follow-up, adjusted for age and year at diagnosis, and DCIS characteristics. In conclusion, overall mortality in women with DCIS is not higher compared to the Dutch female population, though death due to invasive breast cancer is increased. Within all women with DCIS, those with screen-detected DCIS or high SES had lower BCD and all-cause mortality, suggesting a healthy-user effect.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}