Danish Cancer Society

Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols-and its classes and subclasses-and BC risk-overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))-in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HRQ5 vs. Q1 = 1.02; 95% CI: 0.95-1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population.

Lipid transfer proteins (LTPs) maintain the specialized lipid compositions of organellar membranes1,2. In humans, many LTPs are implicated in diseases3, but the cargo and auxiliary lipids that facilitate the transfer of the majority of LTPs remain unknown. Here we combined biochemical, lipidomic and computational methods to systematically characterize LTP-lipid complexes4 and measure how LTP gains of function affect cellular lipidomes. We identified bound lipids for around half of the hundreds of LTPs that we analysed, confirming known ligands and identifying new ones across most LTP families. Gains in LTP function affected the cellular abundance of both their known and newly identified lipid ligands, indicating comparable functional relevance of the two ligand sets. Using structural bioinformatics, we characterized mechanisms that contribute to lipid selectivity and identified preferences based on headgroup or acyl chain. We demonstrate some basic principles of how LTPs mobilize their ligands. They commonly interact with several classes of lipids and exhibit broad but selective preference for particular headgroups and for lipid species with shorter acyl chains that contain one or two unsaturated carbons, suggesting that only subsets of lipid species are efficiently mobilized. The datasets represent a resource for further analysis in different cell types and states, such as those associated with pathologies.

We present the Chromatin Landscape and Structure to Expression Regressor (CLASTER), an epigenetic-based deep neural network that can integrate different data modalities describing the chromatin landscape and its 3D structure. CLASTER effectively translates them into nascent transcription levels measured at a kilobasepair resolution. The model provides a platform to understand the epigenetic drivers and learned rules of nascent transcription, and to predict the impact of in silico epigenetic perturbations. We conclude that the predominant locality of current machine learning approaches emerges as a signature of genomic organization, having broad implications for future modeling approaches.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13059-026-03992-5.

Sex hormones have been implicated in leukemogenesis, but evidence regarding hormonal contraceptive use and leukemia risk remains limited and primarily based on older formulations. Given the widespread use of contemporary hormonal contraceptives, clarification of this potential association is needed. This study examines the association between contemporary hormonal contraceptives and leukemia risk. In a nationwide cohort design, we assessed associations between the use of contemporary hormonal contraceptives and the risk of leukemia based on a cohort of all women aged 15-49 years residing in Denmark from 1995 to 2021 with no previous cancer, hysterectomy, oophorectomy, or sterilization. Information on hormonal contraception use, leukemia diagnoses, and potential confounders (age, calendar year, education) was obtained from nationwide registries. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals [CIs] were estimated for any leukemia, and specific types of leukemia, associated with any hormonal contraceptive use, current and recent use, and previous use, type of product used, duration, and time since last use. Among 1,957,490 pre-menopausal women followed for 24.5 million person-years (median 12.5 years, interquartile range: 5.9,20.5), 671 were diagnosed with leukemia. The incidence rate for leukemia among current and recent users was similar to that among women who had never used hormonal contraception: IRR 0.95 (95% CI [0.78,1.16]; p = 0.62). No association with different durations of use was found: 0-5 years; IRR 0.93 (95% CI [0.75,1.14]; p = 0.48), >5-10 years; IRR 1.16 (95% CI [0.84,1.61]; p = 0.37), >10 years; IRR 0.67 (95% CI [0.33,1.37]; p = 0.27); nor for time since last use: 0-5 years; IRR 1.01 (95% CI [0.78,1.29]; p = 0.96), >5-10 years; IRR 1.05 (95% CI [0.76,1.45]; p = 0.75), >10 years; IRR 0.88 (95% CI [0.60,1.29]; p = 0.52). Also, the IRRs for leukemia with use of different hormonal contraceptive types (e.g., combined products; IRR 0.91 (95% CI [0.73,1.14]; p = 0.42) and progestin-only products; IRR 1.05 (95% CI [0.78,1.40]; p = 0.75)), as well as for product-specific durations of use, were for the majority close to 1. The IRRs were similar for different types of leukemia. Main study limitations include small case numbers in some analyses; therefore, additional large-scale studies are warranted to reliably exclude weak associations. Contemporary hormonal contraceptives were not associated with leukemia, independent of product used, duration of use, time since last use, and type of leukemia. While estimates were imprecise for some subgroups, the overall findings do not support an association.

Caspase-8 is a cysteine protease historically regarded as anti-neoplastic protein, thanks to its role in apoptosis. However, Caspase-8 expression is retained or even enhanced in several tumors, including glioblastoma (GBM), where it plays pro-tumor functions. We previously reported that it is a negative prognostic factor and contributes to resistance against DNA damaging agents, such as ionizing radiations (IR) and Temozolomide, commonly used in standard GBM treatment. We therefore investigated whether Caspase-8 may sustain DNA repair pathways proficiency in GBM. Here we uncover a novel role of Caspase-8 as promoter of the Homologous Recombination Repair (HRR). Importantly, IR promote Caspase-8 transient nuclear translocation and its recruitment to the chromatin. Moreover, Caspase-8 sustains the expression and the recruitment to the chromatin upon IR of RAD51 and CtIP, two key players of the HRR. Consistently, we identify a synthetically lethal interaction between Caspase-8 and PARP inhibition, that may enhance GBM sensitivity to IR. Remarkably, by using Caspase-8-/- murine embryo fibroblasts and a Drosophila melanogaster Caspase-8 mutant, we demonstrate that Caspase-8 plays an evolutionary conserved role in DNA repair.

BackgroundManagement of recurrent glioblastoma (rGBM) remains challenging, particularly for deep-seated or eloquent recurrences not amenable to open surgery, and no standardized effective treatment exists for recurrent disease. European data on MR-guided laser interstitial thermal therapy (LITT) are scarce. This study presents the first Scandinavian experience with LITT for IDH-wild-type rGBM, within publicly funded healthcare systems providing population-wide access to care.MethodsRetrospective data from 30 consecutive patients with histologically confirmed IDH-wild-type rGBM treated with LITT at two Scandinavian centers between January 2019 and May 2024 were analyzed. Demographics, ECOG performance status, procedural parameters, adverse events, and survival outcomes were collected. Kaplan–Meier estimates were used for progression-free survival (PFS) and overall survival (OS).ResultsMean age was 57 years (SD 10.2); 83% had pre-LITT ECOG 0. Complete and ≥ 90% ablation of contrast enhancement was achieved in 83% and 97% of cases, respectively. Median hospital stay was 1 day, with 87% discharged by day 2. Adverse events occurred in 33%, predominantly transient neurological deficits (27%) and infections (7%); 10% had persistent deficits. Median OS after LITT was 13.5 months (95% CI 11.6–20.5) and median PFS was 4.3 months (95% CI 2.6–9.1); 37% remained progression-free at 6 months.ConclusionsLITT was feasible and well tolerated in this two-center Scandinavian cohort, with short hospitalization and low morbidity. Survival outcomes were within the range reported in previous international series. While these findings provide preliminary real-world data on LITT use within Scandinavian publicly funded healthcare systems, the limited sample size and retrospective design preclude definitive conclusions. Prospective, controlled studies are warranted to clarify the clinical role of LITT in recurrent glioblastoma.

BackgroundProcessed meat (PM) consumption is an established risk factor for colorectal cancer (CRC). It has been hypothesized that nitrosyl-heme, formed by the addition of nitrites during meat processing, may enhance the carcinogenic effects of PMs. This study aims to investigate the association between nitrosyl-heme intake and CRC risk within the European Prospective Investigation into Cancer and Nutrition(EPIC) study.MethodsThis prospective study included 367,463 participants(70.3% women) from seven countries from the EPIC-study. Dietary data were collected via baseline questionnaires, and nitrosyl-heme exposure was estimated using biochemical data from 52 Spanish PMs, extrapolated to country-specific items. Sex-specific multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CIs) were calculated using Cox proportional hazards models.ResultsOver a 15-year median follow-up, 5,115 incident CRC cases were identified. Comparing the highest vs. the lowest sex-specific tertile of nitrosyl-heme intake we found no significant association with CRC risk (HRT3vsT1:1.01;95%CI:0.93–1.09). Subgroup analyses by tumor subtype and interactions with lifestyle factors also showed no associations.ConclusionsThis study offers insights into nitrosyl-heme exposure in European populations but found no link to CRC risk. Further research is needed to understand nitrosyl-heme's role in CRC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12937-025-01266-7.