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PubMed2001

Educational opportunities in palliative care: what do general practitioners want?

It is important to support general practitioners (GPs) in maintaining and developing their palliative care skills as most of the final year of a patient's life is spent at home under the care of the primary health care team. The training needs and uptake of GPs have been explored, but little is known about how GP educational preferences vary. The aim of this study was to explore the current educational preferences of GPs in different geographical locations as part of an evaluation of an educational intervention. The methods used included postal questionnaires sent to 1061 GPs. Results from 640 (60%) of GPs revealed that half (51%) wanted education in symptom control for non-cancer patients. More inner-city GPs wanted education in opiate prescribing (43%), controlling nausea and vomiting (45%), and using a syringe driver (38%) than their urban and rural colleagues (26%, 29% and 21%, respectively). Increased educational preference and increased difficulty in accessing information was associated with reduced confidence in symptom control. To maximize educational uptake it will be important for educational strategies to be developed and targeted according to variations in demand, and in particular to respond to the need for palliative care education in symptom control for patients suffering from advanced non-malignant disease.

Adult↗

PubMed1985

Amplified DNA sequences in cancers.

Amplification of genes other than known oncogenes was analyzed using an in-gel DNA renaturation method, in which a mixture of restriction fragments of radioactively labelled tracer DNA and unlabelled driver DNA was electrophoresed and amplified DNA fragments were visualized after two cycles of denaturation and renaturation in the gel. Different DNA fragments were found to be amplified more than 400 fold in NB1, a neuroblastoma cell line, in Y79, a retinoblastoma cell line and in H69, a small cell lung carcinoma cell line, in addition to 120 to 160-fold amplification of N-myc gene in these three cell lines.

Cell Line↗

PubMed1978

Mortality in unionized truck drivers.

To determine occupational mortality in the Central States Teamster population, all death certificates for a three-month period in 1976 were collected and coded. With the exception of respiratory tract cancer and motor vehicle accident deaths, mortality rates were lower than those found in the U.S. population and comparable to those found in other employed populations. It was not possible to separate the effect of cigarette smoking from environmental exposure to explain the excess respiratory tract cancer death. Unexpectedly, the majority of accident mortalities occurred away from work rather than at work.

Accidents, Traffic↗

PubMed2003

Assessment and counseling of older drivers. A guide for primary care physicians.

Despite the proliferation of motor vehicles and the increase in number of miles traveled in this country during the past century, motor vehicle safety has improved. The annual death rate has declined dramatically since it was first measured in 1925. However, motor vehicle accidents remain the leading cause of injury death in children and young and middle-aged adults and the third leading cause of years of potential life lost prior to age 65, behind cancer and heart disease. There are some regional and vehicular factors, with higher motor vehicle death rates in the southeast and in scattered western states. The highest rates of vehicular fatalities are in the youngest and oldest drivers, their passengers, and in all who drive under the influence of alcohol or as a passenger in a car driven by someone under the influence. Medical conditions may also compromise driving ability and/or increase fatality rate in adults of all ages. These conditions and situations, particularly as applied to older adults, are presented here.

Accidents, Traffic↗

PubMed2001

Risk assessment: the importance of genetic polymorphisms in man.

Many genetic polymorphisms in metabolism enzymes are important for the risk of cancer as shown in a large number of case-control studies. The relative risk estimates have shown large variations between such population studies. However, in most studies the relative risk estimates are in the range of 2. Some polymorphisms are effect modifiers, i.e. without exposure they have no consequence and the effect of exposure can appear independent of the genotype. Genetic polymorphisms in metabolism of environmental toxicants plays a significant role in exposures to traffic generated air pollution in Copenhagen, revealing statistically significant higher levels of chromosomal aberrations in non-smoking bus drivers with glutathion-S-transferase M1, GSTM1 null and N-acetyltransferase 2, NAT2 slow genotypes. Combined with cohort studies showing positive associations between high chromosomal levels and increased cancer risk, such results indicate effect modification regarding cancer risk. In risk assessment the safety 'factor' of 10 is generally accepted to allow for variation in individual susceptibility. Reviewing the literature justifies the factor of 10 when considering single polymorphisms. However in an individual with several susceptible metabolism genotypes as well as other determinants of susceptibility, e.g. defective DNA repair, poor-nutritional state, etc. the risk may increase far above a safety of 10.Historically, genetic polymorphisms have been taken into consideration in employment and currently the application in insurance situations is criticised.

Arylamine N-Acetyltransferase↗

PubMed1995

Stomach cancer risk among black and white men and women: the role of occupation and cigarette smoking.

This population-based case-control study assesses the risk of stomach cancer among black and white men and women. The association of occupational risk factors and cigarette smoking with stomach cancer was analyzed using 739 stomach cancer cases and 3750 population controls. Complete occupational and tobacco-use histories were obtained by telephone interview. Significant increases in stomach cancer were observed among black men (odds ratio [OR] = 2.0), white women (OR = 1.7), and black women (OR = 1.4) who had ever smoked. The majority of occupations with significant increases in risk were among white men and included agricultural workers (OR = 2.6), driver sales (OR = 3.8), assemblers (OR = 2.0), mechanics (OR = 2.2), and material movers (OR = 2.9). Black women employed as assemblers (OR = 5.4) and white women employed as food workers (OR = 4.0) also had significant ORs. Evaluating occupations with possible dust exposure, we found no association between dust exposure and stomach cancer.

Adult↗

PubMed1987

Tobacco and occupation as risk factors in bladder cancer: a case-control study in southern Belgium.

A pilot case-control study on bladder cancer, with population-based controls matched for each of 74 cases, has been conducted in two industrial areas of Southern Belgium in order to analyze the influence of tobacco use and occupation. Observed bladder cancer risk for smokers is more than 5 times higher than that for non-smokers, and the risk for people having an a priori hazardous occupation is about 3.5 times higher than that of other subjects. A dose-response relationship was found for tobacco exposure and duration of employment. It seems that the risk is increased in a log-linear way by these variables. Population attributable risks show that in 20 cases of bladder cancer, 17 could be explained by the two factors combined. This study also reveals an increased risk for metal workers, truck and engine drivers, coal-miners, and rubber and coal-tar workers. The risk for metal workers is specially high in the case of turners, metal fitters, blacksmiths, stokers and workers exposed to hot metal.

Adult↗

PubMed2026

High-grade serous ovarian cancer is associated with increased TP53 mutation burden in uterine lavage.

High grade serous ovarian cancer (HGSC) has low survival partly due to the lack of methods for detection, diagnosis, and risk prediction. TP53 mutations, which drive HGSC, are found in gynecological tissues as the result of somatic evolution, but it is unknown whether an excess of mutations is linked to ovarian cancer. Here we investigate if TP53 mutation burden measured in uterine lavage, a minimally invasive gynecological liquid biopsy, can discriminate between patients with and without HGSC. We used ultradeep TP53 duplex sequencing (>15,000x duplex depth) to detect TP53 mutations in uterine lavage collected pre-operatively in 278 patients undergoing gynecological surgery for pelvic masses (average risk) or cancer risk-reduction (high risk). All lavages contained multiple TP53 mutant clones, which were used to quantify TP53 mutation burden frequency (MBF). Average risk patients with HGSC had significantly higher TP53 MBF independently of age and other risk factors (77% sensitivity, 89% specificity, AUC = 0.88). Excluding tumor TP53 clonal mutations from the lavage MBF calculation maintains this association, suggesting that it is the overall TP53 somatic mutation burden (rather than the discovery of the specific tumor driver mutation) that identifies HGSC. These results demonstrate that TP53 somatic mutations are common in uterine lavage but more abundant in patients with HGSC, highlighting a connection between TP53 somatic evolution and ovarian cancer. Uterine lavage offers a minimally invasive approach that could be valuable to identify patients with HGSC.

Journal Article↗

PubMed1992

Life style and occupational risk factors for bladder cancer in Germany. A case-control study.

A hospital-based, case-control study of 531 male and 144 female matched pairs was conducted in Germany to analyze the role of nonoccupational and occupational risk factors in the etiology of tumors of the lower urinary tract (bladder cancer). Smoking of cigarettes was associated with an odds ratio (OR) of 3.6 for men and 3.2 for women, compared with not smoking and showed a significant dose- and time-response relationship for both sexes. Heavy pipe smoking significantly increased the risk (OR = 1.9 in men), and smoking of cigars did not alter the risk of bladder cancer. Controlling for smoking, a significantly twofold or more increase in risk was found for heavy consumption of coffee in both sexes and for heavy intake of beer in males. Increasing levels of total fluid intake were associated with increasing, smoking-adjusted risks in men. Significant associations were found for chronic infection of the lower urinary tract (OR = 1.8), familial history of bladder cancer (OR = 2.5), and frequent consumption of high fat meals (OR = 1.4) among men and for frequent consumption of canned food in both sexes (OR = 1.7 for males, 2.4 for females). With regard to occupational history, significantly elevated odds ratios were found for ever-employment in the printing (5.0), plastics and synthetics (2.6), rubber (2.5), mining (2.0), and dyestuffs (1.9) industries, for exposure to spray paints (2.9), zinc (2.3), chromium/chromate (2.2), oils (1.5), petroleum (1.4), stone dust (1.4) and metal dust/fumes (1.3), and for occupation as mining worker (2.0) and truck driver (1.8) among men. Multivariate logistic regression analysis showed significant contribution of coffee and beer drinking, ingestion of canned food, and familial occurrence of urothelial tumors to the risk of bladder cancer in men after accounting for the effects of tobacco smoking, occupational exposures, and a history of bladder infection. These other variables did not influence the risk attributable to occupational exposures.

Aged↗

PubMed2006

Smoking behavior in trucking industry workers.

BACKGROUND: In retrospective occupational studies, the degree of confounding by smoking depends on variation in smoking among job-related exposure groups. We assessed the relationship between job title and smoking behavior as part of a study on occupational exposures and lung cancer. METHODS: A questionnaire on smoking was mailed to a sample of 11,986 trucking industry workers. Company records were used to gather other relevant information. RESULTS: The response rate was 40.5%. Among white males, the age-adjusted prevalence of ever smoking was highest among longhaul truck drivers (67%) and lowest among clerks (44%). Smoking rates among workers with other job titles were similar. CONCLUSIONS: Our results will be used to adjust for the differences in smoking among job-related exposure groups when assessing the association between particulate matter exposure and lung cancer mortality. Our study also suggests that an assessment of methods to control for smoking should be considered in the design of retrospective occupational health studies.

Aged↗

PubMed2026

Evolution and heterogeneity of lethal metastatic bladder cancer subtypes.

Histological variation is a prognostic feature of metastatic urothelial cancer1-3, but its evolutionary trajectory remains poorly defined. We developed a metastatic bladder cancer rapid autopsy programme enriched in histological subtypes4 to profile individuals with terminal disease. Here by reconstructing the evolutionary histories of patient tumours, we show that metastasis-to-metastasis seeding is the dominant pattern of cancer spread and that increased polyclonal migration predicts poor prognosis. The burden, heterogeneity and timing of genomic alterations differ markedly among histological subtypes. Plasmacytoid and neuroendocrine variants develop early driver alterations associated with shorter survival. Mutational signature analyses and experimental models demonstrated that plasmacytoid tumours uniquely use the Fanconi anaemia pathway to mitigate chemotherapy-induced genomic scarring. Single-nucleus profiling revealed mixed cell states in histological subtypes and an association between transcriptional heterogeneity and patient survival. Characterization of the tumour microenvironment uncovered distinct immune states across subtypes, with plasmacytoid tumours exhibiting immune-inflamed profiles, whereas squamous tumours are predominantly immunosuppressive. Last, we demonstrate that post-mortem cell-free DNA captures genomic and transcriptional heterogeneity of the subtypes, which provides a potential strategy for noninvasive assessment of tumour identity and aggressiveness. Our results provide new insights into how tumour heterogeneity shapes the evolutionary history of disease progression in bladder cancer histological subtypes.

Journal Article↗

PubMed2026

CDC20B Dysregulation: Links to Tumor Prognosis and Immunity.

OBJECTIVE: This study aimed to clarify the pan-cancer expression pattern, upstream regulatory mechanisms, prognostic relevance, and immune associations of CDC20B. METHOD: Using public databases (GTEx, GEO, and TCGA), we examined CDC20B expression and its associations with prognosis and tumor immunity across multiple cancers. Immunohistochemistry (IHC) on an independent clinical cohort was performed to validate CDC20B upregulation in tumor tissues. Promoter methylation, genetic alterations, and immune infiltration were analyzed using bioinformatics tools (cBioPortal, UALCAN, TIMER2.0, ESTIMATE). Functional enrichment was assessed by GSEA and single-cell state analysis (CancerSEA). RESULTS: CDC20B was markedly upregulated in most tumor types (p < 0.001), with strong diagnostic efficiency (AUC > 0.7 in 15 cancers) and potential regulation by promoter hypomethylation. IHC confirmed its overexpression in clinical tumor tissues. However, the prognostic impact of CDC20B was cancer-type-specific: high expression correlated with poor overall survival in UCS, LGG, KIRC, and OV, but with favorable survival in BRCA, LUAD, and PAAD. CDC20B expression was associated with immune infiltration patterns, showing negative correlations with ImmuneScore in most cancers but positive correlations with CD8+ T cells in PAAD. Functional analyses indicated involvement in EMT, KRAS/NF-κB signaling, and DNA damage response pathways. DISCUSSION: The dual prognostic role of CDC20B suggests context-dependent functions, likely influenced by tumor microenvironment composition and underlying oncogenic programs. Promoter hypomethylation emerges as a potential epigenetic driver of overexpression. The associations with immune modulation and genomic instability suggest that CDC20B is a candidate biomarker, though causal relationships require experimental validation. CONCLUSION: CDC20B may contribute to tumor progression in a context-dependent manner, with its prognostic impact varying across cancer types. Its role in tumor immunity and oncogenic pathways warrants further investigation, particularly in stratified patient populations.

CDC20B↗

PubMed1991

Work-related bladder cancer risks in male Japanese workers: estimation of attributable fraction and geographical correlation analysis.

One hundred and forty-nine relative risks (RRs) on occupations and bladder cancer were extracted from 27 case-control studies and geometric means were calculated for 27 occupations as summary RRs. Those in high risk occupations, among whom the summary RRs significantly exceeded unity, were found to be petroleum workers (RR = 3.51), dye workers (RR = 3.38), machinists (RR = 2.76), drivers (RR = 2.22), rubber workers (RR = 2.19), printers (RR = 2.12), clothing/tailors (RR = 2.10), wood workers/carpenters (RR = 1.70), miners (RR = 1.68), textile workers (RR = 1.63), mechanics (RR = 1.54), engineers (RR = 1.54), leather workers (RR = 1.49), painters (RR = 1.48) and chemical workers (RR = 1.44). The estimated numbers of male bladder cancers in 1980 in the high risk and other occupations were 820 and 2065 cases, respectively. The estimated number of work-related bladder cancer was 548 cases, the attributable fraction being 19% in active employees and 12% in the entire population. The geographical distribution of male bladder cancer deaths in Japan was positively correlated with the distributions of workers in the transport/communications industry and in tertiary industries including services, wholesale, retail, finance and insurance, whereas it was negatively correlated with the distribution of workers in the agricultural industry. These findings suggest that workers in certain industries may be at high risk of bladder cancer, but lifestyle modification associated with urbanization and industrialization could be an alternative explanation.

Analysis of Variance↗

PubMed2026

Noncanonical Transcription and Splicing Shape the Colorectal Cancer Immunopeptidome in MSI and MSS Tumors.

Treatment with immune checkpoint inhibitors in colorectal cancer (CRC) has largely benefited patients with microsatellite instability-high (MSI-H) and not the larger proportion of patient with microsatellite-stable (MSS) tumors. This clinical dichotomy has fueled the view that high mutational burden is the dominant driver of tumor immunogenicity and that MSS CRC fails to respond because it is "antigen poor". To directly test this premise and define the origins of presented tumor antigens, we integrated HLA class I immunopeptidomics and matched RNA-seq from 26 primary CRC tumors spanning MSI-H and MSS subtypes. Using patient-specific canonical and cancer-specific proteogenomic databases, we identified 115,292 unique major histocompatibility complex (MHC)-associated peptides (MAPs) across 61 HLA alleles, with a mean of 9292 MAPs per tumor and no significant difference in MAP counts between MSI-H and MSS tumors. In toto, we identified 266 tumor antigens, all coded by unmutated genomic sequences, comprising 70 aberrantly expressed tumor-specific antigens (aeTSAs) and 196 tumor-associated antigens (TAAs). In our cohort, MSS tumors presented more TAAs and a comparable number of aeTSAs per tumor relative to MSI-H tumors. In TCGA-COAD stratified analyses (483 tumors), MSS tumors yielded more presentable aeTSAs and TAAs per patient than MSI-H tumors. Across both subtypes, aeTSAs arose predominantly from intronic translation, UTR usage, retroelement activation, and germline-like transcription, including recurrent aeTSAs from PIWIL1, L1TD1, and endogenous retroviral loci. Together, these data demonstrate that MSS CRC is not antigen poor and highlight noncanonical translation as a major, previously underappreciated contributor to the CRC immunopeptidome.

Humans↗

PubMed2002

Recreational physical activity and ovarian cancer in a population-based case-control study.

Results from epidemiologic studies of physical activity and ovarian cancer have been inconsistent, with 2 prospective studies reporting a modest positive association. We evaluated this relationship in a population-based case-control study conducted in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. Community controls were selected randomly from lists of licensed drivers and Medicare recipients. Participation in moderate and vigorous recreational physical activity at age 12, age 20 and 5 years prior to diagnosis was assessed by telephone interview. Data were available for 327 cases and 3,129 controls. Results were adjusted for age, parity and other ovarian cancer risk factors. Total and vigorous physical activity were not associated with a substantial decrease in ovarian cancer risk at any age. The relative risk (RR) for women reporting > or = 7 vs. 0 hr/week of recent vigorous activity was 0.85 [95% confidence interval (CI) = 0.39-1.86; p for trend = 0.31]. When metabolic equivalent task (MET) hours of activity were estimated, only women in the highest category had any reduction in risk (RR for > 42 MET-hours/week at the reference age = 0.70; 95% CI = 0.36-1.35; p for trend = 0.41). Overall, our results provide only limited support for an inverse association between recreational physical activity and risk of ovarian cancer.

Adult↗

PubMed2025

Investigating the genomic landscape of mouse models of breast cancer metastasis.

Metastasis remains a major cause of cancer mortality. AbstractThis study, expanding upon previous findings in the MMTV-PyMT model, investigated four independent mouse models, representing luminal (MMTV-PyMT, MMTV-Myc), HER2-amplified (MMTV-Her2) and triple negative (C3(1)TAg) breast cancer subtypes. Consistent with previous results, limited evidence for metastasis-associated somatic point mutations was found for all models. We also found that oncogenic drivers significantly influenced the number and size of metastasis-specific copy number variations (MSCNVs), but common driver-independent MSCNVs were rare. Furthermore, analyzing a cohort with varying genetic backgrounds while maintaining a constant oncogenic driver (PyMT) revealed that genetic background profoundly impacts MSCNVs. Transcriptome analysis demonstrated that oncogenic drivers strongly shaped metastasis-specific gene expression (MSGE), with each driver exhibiting distinct expression profiles. In contrast, MSGE in the PyMT-F1 cohort was more variable across strains. Despite the diversity of MSCNV and MSGE, functional analysis revealed that both mechanisms converge on the modulation of key cellular processes, including immune responses, metabolism, and extracellular matrix interactions. These findings emphasize the complex interplay between oncogenic drivers and genetic background in shaping the genomic and transcriptional landscapes of metastatic lesions.

Journal Article↗

PubMed2026

Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs), represented by programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), have shown remarkable efficacy in non-small cell lung cancer (NSCLC); however, many patients still develop resistance to immunotherapy. Although small cell lung cancer (SCLC) is also an important histological type of lung cancer, NSCLC accounts for the majority of lung cancer cases. Current research on ICI development, first-line treatment efficacy, and the mechanisms of lipid metabolism in tumor-associated macrophages (TAMs) is predominantly focused on NSCLC. In patients with advanced NSCLC, objective response rates (ORRs) with PD-1/PD-L1 inhibitor monotherapy remain limited. Only in patients with high PD-L1 expression [tumor proportion score (TPS) ≥50%] and without sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements does the ORR increase to approximately 40-45%. TAMs are a key component of the immunosuppressive tumor microenvironment (TME). Lipid metabolic reprogramming profoundly influences the functional and transcriptional features of TAMs. This review aims to integrate relevant evidence, elucidate how TAM lipid metabolism promotes immunosuppression and resistance to ICIs, and outline potential therapeutic strategies. METHODS: We searched PubMed/MEDLINE, Web of Science, and Scopus for publications up to June 2026 using terms combining lung cancer, TAMs, lipid metabolism, and immune checkpoint blockade/resistance. Mechanistic, translational, and clinically relevant studies were selected by author consensus. KEY CONTENT AND FINDINGS: Lipid uptake, de novo lipogenesis, fatty acid oxidation (FAO), cholesterol remodeling, and eicosanoid metabolism are not independent processes in TAMs. Lipid metabolic reprogramming in TAMs ultimately suppresses type I interferon (IFN-I) signaling, upregulates PD-L1 expression, and impairs the function of CD8+ T cells with stem-like features, thereby establishing an immunosuppressive TME and leading to resistance to ICIs. In lung cancer, hypoxia, high lactate levels, and tobacco exposure further shape the lipid phenotype of TAMs, such as lipid raft enrichment and lipid-laden macrophage subsets like SPP1+ macrophages. Different driver genomic backgrounds differentially impact tumor cell-intrinsic metabolism and the lipid metabolic programs of myeloid cells. In preclinical models, interventions targeting these metabolic axes, including TAM-directed delivery systems, have demonstrated potential therapeutic benefit when combined with anti-PD-1/PD-L1 therapy. CONCLUSIONS: Targeting TAM lipid metabolism to convert immunologically cold tumors into more inflamed, ICI-responsive tumors is a promising strategy to overcome resistance in NSCLC. Identification of predictive biomarkers of therapeutic response and development of cell-selective drug delivery systems come to be major challenges.

Non-small cell lung cancer (NSCLC)↗

PubMed2026

BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance.

Extrachromosomal circular DNA (ecDNA) is frequently generated within the nucleus, contributing to genome dynamics and heterogeneity, thereby promoting cancer cell evolution and adaptation. However, the mechanisms underlying ecDNA biogenesis remain poorly understood. Here, using genome-wide CRISPR screening in human cells, we identified the BRCA1-A and the LIG4 complexes as key drivers of ecDNA production. Following DNA segmentation, the upstream BRCA1-A complex protects DNA ends from excessive resection, promoting end-joining for circularization. Conversely, the MRN complex, which mediates end resection and thus antagonizes the BRCA1-A complex, suppresses ecDNA formation. Downstream, LIG4 conservatively mediates ecDNA production by joining the free ends of the DNA fragments. Furthermore, ecDNA from patient tumors harbors junction sites with a LIG4 signature. Notably, disruption of either LIG4 or the BRCA1-A complex in cancer cells impairs ecDNA-mediated adaptation, hindering the development of resistance to both chemotherapy and targeted therapies. Together, our study reveals the roles of the LIG4 and BRCA1-A complexes in ecDNA biogenesis, and uncovers therapeutic targets to block ecDNA-mediated adaptation for cancer treatment.

Humans↗