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At least 397 records · Page 22Linked to original sources
PubMed2006

Occupational exposure to diesel exhausts and risk for lung cancer in a population-based case-control study in Italy.

BACKGROUND: We studied the effect of exposure to diesel exhausts on lung cancer risk in a population-based case-control study in the city of Turin, Italy. PATIENTS AND METHODS: Information on occupational histories of 595 incident lung cancer cases diagnosed in 1991-1992 and 845 population controls was obtained. During the interviews, diesel job-specific modules (D-JSMs) were administered whenever subjects had worked in occupations included in the following nine categories: railroad workers, miners, professional drivers and transport conductors, heavy-machine operators, mechanics and testers, filling station attendants, motor-vehicle park attendants, transport equipment operators, and occupations carried out in/near urban roads. All D-JSMs were evaluated for probability, intensity and frequency of exposure. RESULTS: The odds ratio for ever exposure to diesel exhausts was 1.04 (95% confidence interval 0.79-1.37), after adjusting for age, sex, smoking and having worked in occupations entailing exposure to known lung carcinogens. No association was found with intensity, probability and duration of exposure. CONCLUSIONS: Although misclassification of the exposure may have contributed to the negative results, we did not find an association between occupational exposure to diesel exhausts and lung cancer risk.

Case-Control Studies↗
PubMed1992

Bladder cancer and occupation in Shanghai, 1980-1984.

To investigate occupational determinants of bladder cancer in the urban area of Shanghai, occupation and industry information for 1,219 incident bladder cancer cases diagnosed during the period 1980 to 1984 were compared with 1982 census data on employment. Standardized incidence ratios (SIR) for bladder cancer were estimated for occupation and industry classifications. Significant excess risks were observed for plastic products workers (male: SIR = 432; female: SIR = 368); textile bleachers, dyers, and finishers (male: SIR = 169); metal refining and processing workers (male: SIR = 139; female: SIR = 197); petroleum refining workers (male: SIR = 2152); railway engine drivers and firemen (male: SIR = 683); and workers employed in industries of apparel and other textile products manufacturing (female: SIR = 204); paper processing (male: SIR = 146; female: SIR = 226); organic chemical manufacturing (male: SIR = 186); plastic product manufacturing (male: SIR = 218; female: SIR = 272); and metallurgy (male: SIR = 107; female: SIR = 561). This study indicates that many of the industries and occupations that are responsible for increased risk throughout the world are also associated with occupational bladder cancer in Shanghai.

Adult↗
PubMed2001

Comprehensive genome sequence analysis of a breast cancer amplicon.

Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus.

Animals↗
PubMed1999

Occupation and histopathology of lung cancer: A case-control study in Rosario, Argentina.

BACKGROUND: Male age-adjusted lung cancer mortality rate is high in Rosario City, Argentina (62.7 per 100,000). METHODS: Case-control study involving interviews with 367 male lung cancer patients and 576 controls. RESULTS: The histological distribution detected was: squamous cell 39%, adenocarcinoma 34%, small cell carcinoma 13%, and other or no specified cell type 14%. When comparing with the group unlikely to be exposed to occupational carcinogens, a 60% increase in risk was observed for the remaining occupations (P < 0.008). Risks were high for drivers (OR=1.9, CI: 1.1-4.0), construction (OR=2.5, CI: 1.0-5.9), and agricultural workers also (OR=1.8, CI: 1. 1-3.1). In regard to squamous cell carcinoma, increased risks were observed in the metal industry, particularly in welders (OR=2.9, CI: 1.0-10.1) and mechanics (OR=1.8, CI: 0.9-4.2). Smoking was not a substantial confounding effect. CONCLUSIONS: Occupational exposures partly account for the high lung cancer mortality rate among male residents of Rosario City.

Adenocarcinoma↗
PubMed2004

Adverse effects of cannabis on health: an update of the literature since 1996.

Recent research has clarified a number of important questions concerning adverse effects of cannabis on health. A causal role of acute cannabis intoxication in motor vehicle and other accidents has now been shown by the presence of measurable levels of Delta(9)-tetrahydrocannabinol (THC) in the blood of injured drivers in the absence of alcohol or other drugs, by surveys of driving under the influence of cannabis, and by significantly higher accident culpability risk of drivers using cannabis. Chronic inflammatory and precancerous changes in the airways have been demonstrated in cannabis smokers, and the most recent case-control study shows an increased risk of airways cancer that is proportional to the amount of cannabis use. Several different studies indicate that the epidemiological link between cannabis use and schizophrenia probably represents a causal role of cannabis in precipitating the onset or relapse of schizophrenia. A weaker but significant link between cannabis and depression has been found in various cohort studies, but the nature of the link is not yet clear. A large body of evidence now demonstrates that cannabis dependence, both behavioral and physical, does occur in about 7-10% of regular users, and that early onset of use, and especially of weekly or daily use, is a strong predictor of future dependence. Cognitive impairments of various types are readily demonstrable during acute cannabis intoxication, but there is no suitable evidence yet available to permit a decision as to whether long-lasting or permanent functional losses can result from chronic heavy use in adults. However, a small but growing body of evidence indicates subtle but apparently permanent effects on memory, information processing, and executive functions, in the offspring of women who used cannabis during pregnancy. In total, the evidence indicates that regular heavy use of cannabis carries significant risks for the individual user and for the health care system.

Accidents, Traffic↗
PubMed2003

Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV breast cancer.

BACKGROUND: In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]). OBJECTIVES: To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective. METHODS: Patient data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles, and adverse events were recorded, with survival follow-up for 12-36 months post-study. Stage IV breast cancer therapy costs were collected by surveying UK oncologists, and utilities for associated health states were from published sources. Costs were in British pounds and year 2000 values. Costs and benefits were jointly determined for the stage IV breast cancer subgroup (n = 55). Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap simulations (10,000 iterations) were conducted to account for uncertainty, and sensitivity analyses were conducted to establish robustness. RESULTS: The ICUR for epoetin-alfa treatment was pounds 8,851 per QALY, with a 99% probability of a positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a 94% probability of being acceptable using a threshold ICUR of pounds 30,000/QALY. The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival. CONCLUSIONS: The available data suggest a high probability of favourable cost-utility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy. Additional studies are warranted.

Adult↗
PubMed2024

Pan-cancer analysis of biallelic inactivation in tumor suppressor genes identifies KEAP1 zygosity as a predictive biomarker in lung cancer.

The canonical model of tumor suppressor gene (TSG)-mediated oncogenesis posits that loss of both alleles is necessary for inactivation. Here, through allele-specific analysis of sequencing data from 48,179 cancer patients, we define the prevalence, selective pressure for, and functional consequences of biallelic inactivation across TSGs. TSGs largely assort into distinct classes associated with either pan-cancer (Class 1) or lineage-specific (Class 2) patterns of selection for biallelic loss, although some TSGs are predominantly monoallelically inactivated (Class 3/4). We demonstrate that selection for biallelic inactivation can be utilized to identify driver genes in non-canonical contexts, including among variants of unknown significance (VUSs) of several TSGs such as KEAP1. Genomic, functional, and clinical data collectively indicate that KEAP1 VUSs phenocopy established KEAP1 oncogenic alleles and that zygosity, rather than variant classification, is predictive of therapeutic response. TSG zygosity is therefore a fundamental determinant of disease etiology and therapeutic sensitivity.

Kelch-Like ECH-Associated Protein 1↗
PubMed1984

Cancer and occupation in Massachusetts: a death certificate study.

This study examines cancer mortality patterns by occupation for white males in Massachusetts using 1971-1973 death records. Its purpose is to identify occupation-cancer associations that, when interpreted in conjunction with results from other studies and hypotheses about potential occupational carcinogens, can serve as leads for more definitive etiological investigations. Sixty-two malignancy categories (including grouped categories) were investigated for each of 397 occupational categories (including grouped categories) using an age-standardized mortality odds ratio approach. An important finding was the association between lung cancer and a large number of occupations for which there is support from other epidemiologic studies and/or for which there are reasonable hypotheses as to possible carcinogenic exposures. These occupations include truck drivers, painters, machinists, automobile mechanics, plumbers, cooks, fishermen, heated metal workers, sheet metal workers, and brickmasons/stonemasons/tile setters.

Adult↗
PubMed1990

Case-control study on occupational exposure to diesel exhaust and lung cancer risk.

The association between lung cancer and occupations with probable exposure to diesel exhaust (DE) was studied among 2,584 cases and 5,099 hospital controls. The crude odds ratio (OR) for probable exposure was 1.31 (95% confidence interval [CI] 1.09-1.57), but adjustment for smoking and other confounders reduced the estimate to 0.95 (95% CI = 0.78-1.16). Similar results were observed for truck drivers, the only occupational category large enough for separate analysis. Data on self-reported exposure for 477 cases and 946 controls revealed a crude OR of 1.45 (95% CI = 0.93-2.27), which was reduced to 1.21 (95% CI = 0.78-2.02) after controlling for smoking and other confounders. The present results and a review of the literature do not definitively support an etiologic association between DE exposure and elevated lung cancer risk.

Adult↗
PubMed2004

[Differentially expressed genes in human giant-cell lung cancer lines with different metastatic potentials].

OBJECTIVE: To screen genes differentially expressed in two human giant-cell lung cancer lines of same origin but with different metastasis potentials. METHODS: Suppression subtractive hybridization (SSH) was done twice on two giant-cell lung cancer lines, PLA-801C and PLA-801D (hereafter abbreviated as C and D), of same origin but with low (C) and high (D) metastatic potentials. In the first round, SSH C was used as tester and D as driver, while in the second round, the tester and driver were interchanged. The sequences acquired from both rounds of SSH were spotted on glass slides respectively and screened by hybridizing with two-color fluorescence probes. Clones that had different expression levels on chips were also confirmed by RNA dot blot or Northern blot. RESULTS: There were 16 sequences with high expression in C as compared to those in D, and 79 sequences with high expression in D compared to those in C. After sequencing, most of them were found to be highly homologous to those encoding the following proteins: (1) cytokines and their receptors; (2) kinases and related proteins; (3) other proteins including enzymes, heat shock proteins, receptors, proteins of cell skeleton and mitochondria, products of oncogenes, etc; (4) some proteins deduced from gene sequences with yet unknown functions. CONCLUSION: The alterations in expression of some known genes, including HSP70, AXL receptor tyrosine kinase and 14-3-3zeta, might have impact on metastasis of giant-cell lung cancer. Whether some differentially expressed genes newly revealed are metastasis-related needs further study.

14-3-3 Proteins↗
PubMed2026

Impact of Tumor Genomic Profile on Adjuvant Chemotherapy Efficacy in Resected Pancreatic Adenocarcinoma: Results From the PRODIGE-24/CCTG PA6 Study.

PURPOSE: Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX/mFFX) is the standard adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), offering survival benefits over gemcitabine (GEM). However, the contribution of molecular biomarkers to treatment selection remains unclear. Here, we characterize the molecular landscape of tumors from the PRODIGE-24/CCTG PA6 trial and assess the clinical impact of genomic alterations and molecular subtypes. PATIENTS AND METHODS: Tumor DNA sequencing was successfully performed in 317/350 tumors (168 mFFX; 149 GEM), complemented by transcriptomic subtyping using the PurIST classifier. Mutational status of four key PDAC driver genes and 24 homologous recombination repair (HRR)-associated genes was analyzed, alongside single-base substitution (SBS) mutational signatures. Primary and secondary end points were disease-free survival (DFS) and cancer-specific survival (CSS), respectively. RESULTS: In the mFFX group, the PurIST subtype was prognostic, with classical tumors showing superior DFS compared with basal-like tumors (stratified hazard ratio [sHR], 0.48 [95% CI, 0.31 to 0.77]). Among KRAS-mutated patients, mFFX significantly improved DFS compared with GEM (sHR, 0.60 [95% CI, 0.45 to 0.79]; P < .001), while no benefit was observed in KRAS wild-type tumors (interaction test, Pint. = 0.010). HRR and BRCA status were not predictive (Pint. = .568 and Pint. = .785, respectively). The benefit of mFFX was consistent across SBS-positive and SBS-negative subgroups. CONCLUSION: Overall, these results do not support a change in current adjuvant treatment strategies. mFFX remains the standard adjuvant regimen in PDAC, and the observed lack of benefit in KRAS wild-type tumors should be considered hypothesis-generating and warrants further investigation.

Humans↗
PubMed2026

Establishment of Stable Immortalized Human Choroidal Melanocytes for Ocular Research.

PURPOSE: The short lifespan of primary normal choroidal melanocytes (NCMs) in vitro represents a major barrier to mechanistic, functional, and translational studies of choroid biology and uveal melanoma (UM). This study aimed to establish and characterize immortalized human NCM lines that retain melanocytic function, maintain a non-cancerous profile, and are amenable to gene editing. METHODS: NCMs from four donors were immortalized by lentiviral transduction of cyclin-dependent kinase 4 (CDK4R24C), cyclin D1, and human telomerase reverse transcriptase (hTERT), establishing NCM-K4DT lines. Their morphology, melanocytic marker expression, proliferation, and functional properties (melanin synthesis and tyrosinase activity) were evaluated. Genomic stability was assessed by targeted mutation profiling, karyotyping, and copy number variation (CNV) analysis. The tumorigenicity was tested in immunodeficient mice. Plasmid-based CRISPR/Cas9 editing was performed to determine their suitability for gene editing. RESULTS: NCM-K4DT lines retained dendritic-shaped morphology, pigmentation, and expression of PMEL, TYRP1, Melan-A, and SOX10. Cells exhibited enhanced proliferative capacity with preserved cell cycle regulation. Melanin production and tyrosinase activity were comparable to primary NCMs. Genomic profiling confirmed the absence of UM-associated driver mutations and chromosomal abnormalities. In vivo growth assays demonstrated that NCM-K4DT lines did not form tumors within the 3-month observation period. Notably, NCM-K4DT cells were efficiently edited by CRISPR/Cas9. CONCLUSIONS: NCM-K4DT lines represent stable, non-cancerous, and genetically tractable models for studying choroidal melanocyte biology, modeling UM-associated mechanisms, and advancing therapeutic development in ocular research.

Humans↗
PubMed2024

Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach.

Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.

Kidney Neoplasms↗
PubMed2003

The effect of donepezil on sedation and other symptoms in patients receiving opioids for cancer pain: a pilot study.

Opioid-induced sedation is a major complication in patients with cancer pain. This study assessed the effectiveness of donepezil in opioid-induced sedation and related symptoms in patients with cancer pain. Twenty-seven patients who were receiving strong opioids for pain and reported sedation were enrolled. Donepezil 5 mg was given every morning for 7 days. Changes between baseline and Day 7 in sedation, pain, fatigue and other symptoms were evaluated using the Edmonton Symptom Assessment Scale. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Overall usefulness of donepezil was measured by the patient at the end of the study. In 20 evaluable patients, sedation, fatigue, anxiety, well-being, depression, anorexia and problems with sleep were significantly improved. Side effects included nausea, vomiting, diarrhea, muscle and abdominal cramps, and anorexia. Overall, however, the treatment was well tolerated. Donepezil appears to improve sedation and fatigue in patients receiving opioids for cancer pain. Randomized controlled trials of this agent are justified.

Adult↗
PubMed1998

[Oncogenes--"reckless drivers" on signal pathways controlling cell division].

Today, about 20 years after the discovery of cellular genes with oncogenic potential, we possess substantial knowledge on the regulation of normal cell growth and division. At the same time, we have gained insight into the loss of growth control which occurs in cancer cells. The following is a brief review of the progress made in oncogene research and the knowledge we have gained. It is important to stress that our understanding of the cellular and molecular mechanisms involved is still in its infancy. However, pieces are being added to the puzzle at an increasingly faster pace, primarily because of the progress in gene technology during the last two decades. Research methods have been set up to allow greater cooperation across disciplinary boundaries, thus increasing the speed with which important discoveries occur. A goal for the future will be to identify all oncogenes and tumor suppressor genes and elucidate their functions. At the same time, one of the major challenges will be to translate the knowledge thus gained into the development of more powerful and specific therapeutic strategies. As a result of the increasing insight gained by modern oncogene research, the need for detailed cancer diagnostics based on molecular genetics will increase significantly in the future.

Animals↗
PubMed2003

Methylation-sensitive representational difference analysis and its application to cancer research.

Methylation-sensitive representational difference analysis (MS-RDA) was previously established to detect differences in the methylation status of two genomes. This method uses the digestion of genomic DNA with a methylation-sensitive restriction enzyme, HpaII, and PCR to prepare "HpaII-amplicons," followed by RDA. An HpaII-amplicon prepared using betaine and reverse electrophoresis was enriched 3.6-fold (compared with the HpaII-amplicon prepared by the original method) with DNA fragments originating from CpG islands (CGIs). As for the specificity of MS-RDA, it was shown that DNA fragments that are unmethylated in the tester and almost completely methylated in the driver are efficiently isolated. This indicated that genes that are in biallelic methylation or in monoallelic methylation with loss of the other allele are efficiently isolated. Further, by use of two additional methylation-sensitive six-base recognition restriction enzymes, SacII and NarI, more DNA fragments were isolated from CGIs in the 5' regions of genes. After analysis of human lung, gastric, and breast cancers, 12 genes were seen to be silenced and additional genes seen to show decreased expression in association with methylation of genomic regions outside CGIs in the 5' regions of genes. MS-RDA is effective in identifying silenced genes in various cancers.

Base Sequence↗
PubMed1990

Occupational risks of thyroid cancer: data from the Swedish Cancer-Environment Register, 1961-1979.

Using data from a record-linkage between the Swedish population census of 1960 and the Swedish Cancer Registry, we performed an explorative, hypothesis-generating analysis of the incidence of thyroid cancer in 208 occupations and 231 industries. Relative risks were computed with adjustment for age, period of follow-up, and geographic region. A total of 1,230 male and 2,937 female cases of thyroid cancer were reported during 1961-1979 among individuals aged 20-69 years in 1960. As a group, male blue-collar workers had a lower reported incidence than other men. Significantly elevated risks were seen among drivers, pharmacists, workers in the canning and preserving industry, workers in the petroleum industry, and among X-ray operators and laboratory assistants. Horticulture workers, painters in the construction industry, and unskilled manual workers showed decreased risks.

Adult↗
PubMed2000

RaSH, a rapid subtraction hybridization approach for identifying and cloning differentially expressed genes.

Human melanoma cells growth-arrest irreversibly and terminally differentiate on treatment with a combination of fibroblast interferon and the protein kinase C activator mezerein. This experimental protocol also results in a loss of tumorigenic potential and profound changes in gene expression. Various cloning and cDNA microarray strategies are being used to determine the complete spectrum of gene expression changes underlying these alterations in human melanoma cells. An efficient approach, Rapid Subtraction Hybridization (RaSH), has been developed that is permitting the identification of genes of potential relevance to cancer growth control and terminal cell differentiation. RaSH cDNA libraries are prepared from double-stranded cDNAs that are enzymatically digested into small fragments, ligated to adapters, and PCR amplified followed by incubation of tester and driver PCR fragments. This subtraction hybridization scheme is technically simple and results in the identification of a high proportion of differentially expressed sequences, including known genes and those not described in current DNA databases. The RaSH approach represents an efficient methodology for identifying and cloning genes displaying differential expression that associate with and potentially regulate complex biological processes.

Base Sequence↗