British Journal of Cancer最新文献

Background: The ProsD trial aimed to determine if oral vitamin D supplementation could prevent prostate cancer (PC) progression in men on active surveillance (AS).

Methods: ProsD is a phase-II double-blinded randomized trial of newly diagnosed, low-intermediate risk PC cases, aged between 50 and 80 years and on AS. The intervention was a monthly oral dose of cholecalciferol (50,000IU; Vitamin D) or placebo. Primary and secondary endpoints were active therapy-free (ATFS) and progression-free (PFS) survival, respectively. Blood samples were analysed for vitamin D metabolites and cytokinesis-block micronucleus cytome (CBMN) markers for lymphocytic genome damage.

Results: There were 123 randomised participants (81 vitamin D and 42 placebo) included in this analysis. Mean (SD) for age was 66.5 (6.6) years and for 25(OH)D levels were 72.0 (19.9) and 66.4 (18.4) nmol/L at baseline (p = 0.1), and 91.9 (19.9) and 60.4 (24.4) nmol/L at 24 months, in the vitamin D and placebo arms respectively. There were no appreciable differences in ATFS (p_log-rank = 0.44), PFS (p p_log-rank = 0.60) and occurrence of adverse events, in each trial arm. There were declines in some of the lymphocytic CBMN markers in the vitamin D arm.

Conclusion: Vitamin D supplementation did not prevent PC progression, although reduced prevalence of CBMN markers may indicate a benefit of vitamin D supplementation.

Trial registration: Australia New Zealand Clinical Trials Registry (ACTRN12616001707459).

Background: Colorectal cancer (CRC) incidence is rising among adults under 55 years, but its causes remain unclear. Large-scale prospective studies are needed to identify risk factors for early-onset CRC (EOCRC).

Methods: We pooled three large European prospective cohort studies, examining 14 known or suspected risk factors with EOCRC (diagnosed <55 years, N = 1369) and later-onset CRCs (LOCRC) (diagnosed ≥55 years, N = 13,490). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Higher body mass index (BMI, per 5 kg/m² increase), was strongly associated with EOCRC in men (HR 1.33, 95% CI: 1.18-1.51), particularly for early-onset colon cancer (HR 1.55, 95% CI: 1.32-1.82), compared to later-onset disease (HR 1.25, 95% CI: 1.19-1.31) (Phet = 0.01). Weaker associations with BMI were observed for women and rectal cancers. Similar sex and subsite specific trends were observed for waist circumference and waist-to-hip ratio. Current smoking (HR 1.24, 95% CI: 1.07-1.44) and alcohol use (HR 1.15, 95% CI: 1.06-1.25) increased EOCRC risk, and physical activity (HR 0.71, 95% CI: 0.54-0.95) was protective.

Discussion: Adiposity, physical inactivity, smoking, and alcohol consumption are risk factors for EOCRC. Risk factors were largely similar between EOCRC and LOCRC, except for adiposity, with stronger EOCRC association in men.

In 2022, Hanahan integrated polymorphic microbiomes to the hallmarks of cancer, resulting in 14 overarching features that are considered fundamental to initiation and progression of cancers. It is well acknowledged that genomic instability/genetic alterations together with tumor-associated inflammation are so called "enabling hallmarks" as they drive the acquisition of the other traits. The microbiome is a key component of the inflammatory tumor stroma. Pancreatic ductal adenocarcinoma (PDAC) in particular is characterized by a pronounced stromal compartment whose role in the acquisition of malignant properties is well documented. Recent studies indicate massive alterations of the microbiome in PDAC tissues compared to healthy pancreas or precursor lesions. However, the mechanistic role of the PDAC-associated microbiome, its influence on the hallmarks of cancer, and how this relates to PDAC malignancy remain poorly understood. This raises the question of whether the tumor-associated microbiome through its direct influence on PDAC cells, their precursors, and the surrounding non-neoplastic cells promotes the acquisition of other hallmarks that drive PDAC development and progression. This perspective article outlines the current knowledge of the impact of the PDAC-associated microbiome on the hallmarks of cancer in PDAC. These current findings support the altered microbiome as a third enabling hallmark of PDAC and emphasize that further mechanistic studies are urgently needed to further substantiate its fundamental importance for this tumor entity. This knowledge will provide the basis for clinical translation to develop more effective therapeutic approaches for PDAC. The intratumoral microbiome in PDAC exhibits numerous interactions with the hallmarks of cancer. Hallmarks indicated in blue have demonstrated interactions with the microbiome, while others still remain underexplored. These extensive interactions substantiate the role of the intratumoral microbiome in PDAC as an enabling hallmark, underlining its potential as a therapeutic target. Partially created with biorender.com.

Hepatocellular carcinoma (HCC) relapse remains high after curative-intent treatment due to occult minimal residual disease. Circulating tumour DNA (ctDNA) has emerged as a noninvasive biomarker. Systematic search of MEDLINE, EMBASE and the Cochrane Library up to November 2024 identified studies evaluating plasma ctDNA in non-metastatic HCC patients undergoing curative-intent treatment. Hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using random-effects models; sensitivity and specificity for predicting recurrence were summarised. Ten retrospective studies (n = 793) met inclusion criteria. Postoperative ctDNA positivity was associated with shorter RFS (HR 4.48; 95% CI 2.56-7.82; I² = 78%; p < 0.001) and worse OS (HR 2.99; 95% CI 1.94-4.61; I² = 47%; p < 0.001). Baseline ctDNA detection predicted reduced RFS (HR 3.54; 95% CI 1.97-6.38; I² = 35%; p < 0.001). Sensitivity ranged 33-82% and specificity 41-100%, reflecting methodological heterogeneity. Leave-one-out analyses confirmed robustness. Plasma ctDNA is a potent prognostic marker of recurrence and survival in non-metastatic HCC. Prospective trials incorporating ctDNA could optimise postoperative surveillance and guide adjuvant therapy selection.