International Journal of Cancer最新文献

The purpose of cancer screening is to reduce mortality, and ideally incidence, from the cancer screened for. Until recently, cancer screening has been offered to all persons in pre-defined sex- and age-groups. The exception is lung screening which is targeted to high-risk individuals. Evidence for effect of screening on cancer-specific mortality is available for cancer of the cervix, breast, colorectal, lung, and prostate, and on cancer-specific incidence for cervix and colorectal cancer. With more effective molecular and computational tools, the current paradigm of cancer screening will change. Manual reading of images and pathology in mammography, cytology, colposcopy, colonoscopy, and CT scan will be complemented or replaced by AI-interpretation. Risk stratification will diversify screening intensity, for instance in breast screening where modelling and randomized controlled trials are underway. Blood-based screening tests might allow for simultaneous early detection of several types of cancer. Furthermore, prediction models based on life trajectories in health and other data will enhance risk stratification, potentially dividing the population into groups with no need of screening, with need of simple or advanced screening, with need of surveillance or even diagnostics. In public health care systems, these developments must be closely monitored. Before replacing an existing program, evidence for non-inferiority in reducing cancer-specific mortality should be ensured. Benefits must outweigh harms, and citizens should have confidence in new screening schemes. With the pressure on health care resources, screening should continue in organized and monitored programs. Taking these conditions into account, the new screening tools will potentially enable improved cancer control.

Patients with lung squamous cell carcinoma (LUSC) are often diagnosed at advanced stages, limiting opportunities for early intervention. LUSC develops through multistep progression from low-grade lesions to high-grade lesions, including carcinoma in situ (CIS), of which about half progress to invasive cancer while the other half regress. Although frequent mutations and copy number alterations have been documented in LUSC and observed in precursor lesions, their prognostic significance in precancers remains largely unexplored. In this study, we leveraged gene expression data from LUSC tumors in The Cancer Genome Atlas to derive transcriptional signatures corresponding to 34 key driver genomic aberrations, including mutations, amplifications, and deletions. These tumor-derived signatures were applied to precancerous datasets to assess their ability to characterize developmental stages and predict progression risk. We found many of these signatures increased progressively across lesion stages, reflecting roles in early tumorigenesis. In particular, several signatures accurately predicted which CIS lesions would progress to invasive cancer. Furthermore, these signature scores were more strongly associated with prognosis in LUSC than the presence of genomic aberrations alone. We also examined relationships between driver-associated signatures and the tumor immune microenvironment. Signature scores were significantly correlated with immune features such as immune cell infiltration and immune checkpoint gene expression, including CD274 (PD-L1). These associations varied across stages, indicating dynamic immune interactions during cancer evolution. Together, our findings demonstrate that tumor-derived driver gene expression signatures provide valuable insight into the biology and progression risk of precancerous lesions, offering potential utility for early detection and intervention in LUSC.

Pancreatic cancer (PCA) is the third leading cause of cancer-related death in Europe. Despite recent therapeutic advances, patients experience rapid health deterioration. Based on previous results, the Platform for Outcome, Quality of Life, and Translational Research on Pancreatic Cancer-PARAGON (NCT04119362) was initiated to investigate the whole life cycle of PCA patients. Between November 2019 and October 2021, 469/479 screened patients were enrolled in 46 sites. Demographic, clinical, and quality of life (QoL) data were collected. The treatment landscape was depicted using Sankey diagrams. Median overall survival (mOS) for all patients in first line was 10.6 months (95% confidence interval [CI], 9.2-11.7 months). With mFOLFIRINOX as first-line treatment, mOS was 11.3 months (95% CI, 8.6-13.5 months), with gemcitabine/nab-paclitaxel 10.5 months (95% CI, 8.3-12.9 months). The mean Global Health Status for patients that proceeded from first to second line did not substantially deteriorate during first line. Predictive variables for proceeding from first to second-line therapy were reasons for ending first-line treatment (patient's wish, toxicity, and progressive disease) and age. In summary, we were able to show in detail patient flows and QoL data throughout all therapy lines, which will help to further understand the major clinical checkpoints of the disease.

Most cutaneous malignant melanomas (CMMs) are thin (≤1.0 mm, stage T1) with an expected 10-year melanoma-specific survival of 93%-97%. The incidence of CMM is higher in groups with high socioeconomic status (SES). We aimed to assess overall survival (OS) and detailed characteristics in individuals with thin CMM as compared to the general population matched on age, sex, and county of residence. Matched cohort study comprising patients diagnosed between 2001 and 2018 with thin CMM (cases) and melanoma-free comparators from the general population. Patients and comparators were identified in the Malignant Melanoma Data Base Sweden. Multivariable Cox regression analyses were applied to compare the mortality risk for cases and comparators with adjustments for SES and comorbidities. We identified 25,843 cases and 127,383 comparators. Cases had higher SES and less comorbidity. No significant differences in OS were found. However, in the T1a subgroup, comprising 16,941 cases, the 5-year OS was significantly better than in comparators (n = 83,510) (92.5% (95% CI 92.1%-93.0%) versus 91.1% (95% CI 90.8%-91.3%), p <.001). The adjusted mortality risk was slightly higher for the whole T1 group (HR 1.05, 95% CI 1.01-1.09), while no difference was found for the T1a subgroup. Deaths attributed to cardiovascular disease, dementia, and chronic obstructive pulmonary disease were less common in CMM patients. Patients diagnosed with thin CMM have an OS similar to or even better than the general population since they are at a lower risk of death from other diseases, likely reflecting socioeconomic and lifestyle factors.

This study examined the associations of diabetes status, duration, and age at onset with lung cancer risk in the China Kadoorie Biobank. We prospectively assessed the association between diabetes status and lung cancer risk in 510,148 cancer-free participants, with analyses of duration and age at onset among 29,962 participants with diabetes at baseline. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models, and effect modification was assessed across stratified subgroups using likelihood ratio tests. During a median 9.17-year follow-up, 5007 lung cancer cases occurred. Compared with participants without diabetes, those with diabetes had a higher lung cancer risk (HR = 1.15, 95% CI: 1.01-1.32). Diabetic patients with onset <40 years showed a 2.81-fold higher lung cancer risk (95% CI: 1.31-6.02) compared to ≥60-year onset groups. Longer duration (≥15 vs. <1 year) was associated with increased risk (HR = 2.06, 95% CI: 1.33-3.19). The association with diabetes status was stronger among individuals with below-median physical activity, while the association with diabetes duration was more pronounced in overweight participants. Overall, these findings indicate that diabetes, especially with earlier onset and longer duration, significantly increases lung cancer risk, highlighting the need for screening and targeted management in high-risk populations.

Benefits and harms of breast cancer (BC) screening with mammography have been debated and, although most studies reported positive effects, some studies found a negative effect in terms of net quality-adjusted life years (QALYs). We aimed to estimate net QALYs associated with biennial mammographic screening for women aged 50-69 years offered to 100,000 women followed until age 85, using various assumptions on BC mortality reduction, overdiagnosis and mortality transfer (the extent to which a reduction in BC mortality results in a reduction in all-cause mortality). Individual-level data from women invited to BreastScreen Norway during 1996-2020 were used to perform the calculations. The three baseline scenarios included (1) Model Microsimulation Screening Analysis (MISCAN): MISCAN prediction for mortality reduction and overdiagnosis proportion; (2) Model A: 40% BC mortality reduction and 15% overdiagnosis; and (3) Model B: 20% BC mortality reduction and 50% overdiagnosis. For all scenarios, an 80% mortality transfer was assumed. An online tool was developed to illustrate the impact of alternative assumptions. Biennial organized mammographic screening for women aged 50-69 years who were followed until the age of 85 years was associated with 6819, 7444 and 2446 net QALYs gained per 100,000 women for Model MISCAN, A and B, respectively. Assumptions on BC mortality reduction exhibited the largest impact on net QALYs. To conclude, even when assuming a high overdiagnosis proportion and low BC mortality reduction, net QALYs remained positive, reinforcing the value of offering BC screening with mammography to Norwegian women and showing its potential to improve health outcomes.

Exercise protects against colon cancer progression, but the underlying biological mechanisms remain unclear. One proposed mechanism is the release of bioactive molecules into the systemic circulation during exercise, which may act directly on tumour cells to suppress DNA damage, inhibit proliferation, and preserve genomic stability. Here, we profiled the serum proteomic response to acute exercise and evaluated the effects of exercise-conditioned human serum on DNA damage kinetics and transcriptomic signatures in colon cancer cells. Blood samples were collected from 30 overweight/obese adults before and immediately after a maximal incremental cycling test. LoVo cells were exposed to pre- or post-exercise serum, treated with 2 Gy irradiation, and assessed for γ-H2AX foci over 24 h. Acute exercise increased the relative abundance of 13 proteins in serum (p < 0.05), including interleukin-6 (IL-6) and its soluble receptor IL-6R, reflecting systemic activation of acute-phase immune and vascular signalling. Compared to pre-exercise serum, post-exercise serum significantly reduced γ-H2AX foci in LoVo cells at 6 h (p = 0.010) and decreased the area under the curve (p = 0.014), indicating accelerated DNA repair. Post-exercise serum also increased expression of the DNA repair gene PNKP, with and without irradiation (p = 0.007 and p = 0.029, respectively). Transcriptomic analysis revealed upregulation of mitochondrial energy metabolism and downregulation of cell cycle and proteasome-related pathways. These findings suggest that acute exercise elicits systemic responses that enhance DNA repair and shift colon cancer cells towards a less proliferative transcriptomic state under sublethal genotoxic stress, offering a potential mechanistic explanation for the protective effects of exercise against colorectal carcinogenesis.