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PubMed1985

Mortality patterns among U.S. veterans by occupation. I. Cancer.

The mortality experience of a nation-wide cohort of 293,958 veterans was analyzed by occupation and industry to generate hypotheses in occupational cancer. Results are presented on 107,563 deaths occurring between 1954 and 1970. Information on usual employment (occupation and industry) and smoking habits was available from questionnaires completed in 1954 and 1957. Complete enumeration of these results by occupation and industry is available as special National Cancer Institute monographs from the author (A. B.). This report presents the mortality experience for selected occupations. Excesses of lung cancer among shipyard workers, truck drivers, and plumbers are consistent with previous reports. Elevated risks for stomach cancer among carpenters and machinists may reflect exposure to dusts, abrasives, and cutting oils.

Adult↗
PubMed2025

Relationship Between Cognitive Disorder and First-Line Targeted Therapy for Oncogene Driver-Positive Patients With Non-Small Cell Lung Cancer: Prospective Cohort Study.

BACKGROUND: Previous studies have found and confirmed a correlation between cognitive disorder and chemotherapy. As genetic testing becomes more routine in clinical practice, targeted therapies are increasingly gaining prominence. The relationship between targeted treatment and cognitive function is not yet clear. This study aimed to investigate the correlation between cognitive disorder and targeted treatment by evaluating the changes in cognitive function before and after targeted therapy. OBJECTIVE: This study aims to explore whether targeted therapy affects cognitive function in patients with advanced lung cancer and to explore the association between cognitive function, the inflammatory biomarker C-reactive protein, and psychological stress. METHODS: From the screened cohort of 150 patients with advanced non-small cell lung cancer (NSCLC) with gene mutations, 87 (58%) were rigorously selected for the study. The evaluation instruments used were the Mini-Mental State Examination scale, the Distress Thermometer, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 for assessing quality of life. RESULTS: A significantly lower progression-free survival (PFS) was observed in the group of patients surviving advanced NSCLC with cognitive disorder under targeted therapy in contrast to survivors in the group with no cognitive disorder (hazard ratio=0.347, 95% CI 0.209-0.578; P<.001). Furthermore, the objective response rate and disease control rate for the group with cognitive disorder were noted to be 37.8% and 86.7%, respectively, contrastingly lower than those in the group with no cognitive disorder, recorded at 78.6% and 97.6%, respectively. Significant variances were also noted in the Mini-Mental State Examination scores between patients with and without cognitive disorder both before and after targeted therapy (P<.001 in both cases), with a decreasing trend observed in both groups after targeted therapy. Noteworthy differences were found in quality of life scores both before and after targeted therapy (P<.001 in both cases). In addition, notable disparities were apparent in C-reactive protein levels among the 2 groups before and after treatment (P=.03 and P=.048 for each time point, respectively), with an upward trend observed in both groups after targeted therapy. The multivariate Cox regression analysis demonstrated that cognitive function is an independent risk factor for PFS in patients with NSCLC receiving targeted therapy. CONCLUSIONS: Cognitive disorder may lead to lower quality of life scores and shorter PFS in patients undergoing targeted therapy. Early screening and intervention for such patients could effectively improve clinical outcomes and quality of life.

Humans↗
PubMed1982

The utility of regional cancer mortality data for identifying occupations at high risk.

Mortality rates by geographic areas have been used successfully in the past to identify occupations with a high risk of cancer. The 1975 Atlas of Cancer Mortality for U.S. Counties: 1950-1969 for white males showed that mortality rates in three California counties (Alameda, Sacramento, and San Francisco) were significantly elevated compared to other US counties, and in Sacramento County the lung cancer death rate was significantly high also. This current study was to determine if the excess in the cancer mortality rate found in Sacramento County was possibly related to specific occupational categories. Death certificates for all white males dying of cancer were retrieved, Last occupation, industry, and length of service were coded according to the Index of Industries and Occupations prepared by the US Bureau of the Census. Observed frequencies of cancer deaths were compared to an expected number which was based on US census data by occupation for Sacramento County. Elevated standardized mortality ratios (SMRs) for cancer deaths were found for technicians, metal craftsmen, nonfarm laborers, construction workers, and drivers. SMRs were high for cancer of the esophagus, pancreas, respiratory tract, skin, and central nervous system.

Adult↗
PubMed2003

cDNA suppression subtraction library for screening down-regulated genes in gastric carcinoma.

AIM: To establish cDNA suppression subtraction library with a high subtraction efficiency by counterpart normal gastric mucosa mixture mRNA subtracting gastric cancer cells mixture mRNA for screening down-regulated genes in gastric carcinoma. METHODS: RNA of gastric cancer tissues and counterpart normal gastric mucosa were respectively isolated in five patients with gastric cancer, and their mRNA was purified. cDNA suppression subtraction library was established by counterpart normal gastric mucosa mixture mRNA (tester) subtracting gastric cancer tissues mixture mRNA (driver) of five patients with gastric carcinoma. The library plasmids were transformed into competent bacteria DH5a after ligation of the library cDNA fragments with T vectors. Library plasmids were extracted after picking colonies and shaking bacteria overnight. Its subtraction efficiency was confirmed by PCR and reverse hybridization of a nylon filter onto which the colonies of bacteria were transferred with probes of reverse transcription products cDNA of gastric cancer tissues mRNA and counterpart normal gastric mucosa mRNA labeled with alpha- (32)P dCTP. RESULTS: mRNA purified from total RNA of gastric cancer tissues and counterpart normal gastric mucosa in five patients with gastric carcinoma revealed a good quality. cDNA suppression subtraction library constructed for screening down-regulated genes in gastric carcinoma represented a high subtraction efficiency. 86 % of differential expression in down-regulated genes between counterpart normal gastric mucosa and gastric carcinoma was confirmed. CONCLUSION: cDNA suppression subtraction library with a high subtraction efficiency for screening down-regulated genes in gastric carcinoma is successfully established.

Cloning, Molecular↗
PubMed1994

Mortality among taxi drivers in Rome: a cohort study.

The mortality pattern of taxi drivers in Rome as possibly exposed mainly to gasoline engine exhausts was evaluated by means of a historical cohort study. A total of 2,311 male subjects registered as taxi drivers between 1950 and 1975 was followed from 1965 through 1988. The overall mortality was lower than expected on the basis of regional (Latium) reference rates (692 deaths, standardized mortality ratio [SMR] = 0.89, 95% confidence interval [CI] 0.82-0.96), whereas the number of recorded deaths for malignant neoplasms was about the expected (205 deaths, SMR = 0.99, 95% CI 0.86-1.13). Mortality from circulatory and respiratory diseases was lower than expected. Diabetes was significantly increased (42 deaths, SMR = 1.73, 95% CI = 1.25-2.34). An increased SMR appeared for respiratory cancer (SMR = 1.23, 95% CI = 0.98-1.50), mainly due to lung cancer (observed [O] = 76, SMR = 1.23, 95% CI = 0.97-1.54); two pleural cancers were also recorded. The excess of lung cancer deaths was present only among those enrolled in the most recent period (1965-1975) (45 deaths, SMR = 1.40, 95% CI = 1.02-1.87), especially among those of younger age (< 65 years) (SMR = 1.86); there was no relation between lung cancer mortality and latency since first enrollment in the cooperatives or duration of membership. There are difficulties in interpreting the excess of lung cancer on the basis of occupational exposures; however, the increased risk observed among workers employed in more recent calendar periods may be due to heavier exposure in the last decades; further follow-up of the cohort may elucidate whether there is an increasing lung cancer risk among taxi drivers.

Adolescent↗
PubMed2025

Integrating mutation, copy number, and gene expression data to identify driver genes of recurrent chromosome-arm losses.

Aneuploidy is a hallmark of cancer, yet the genes driving recurrent chromosome-arm losses remain largely unknown. We present a systematic framework integrating mutation, copy number, and gene expression data to identify candidate driver genes of cancer type-specific recurrent chromosome-arm losses across 20 cancer types, using &#x223c;7,500 tumors from The Cancer Genome Atlas. By analyzing focal deletions and point mutations that co-occur, or are mutually exclusive, with chromosome-arm losses, we pinpoint 322 candidate drivers associated with 159 recurring events. Our approach identifies known aneuploidy drivers such as TP53 and PTEN, while revealing multiple additional candidates, including tumor suppressors not previously linked to aneuploidy. We leverage expression changes associated with chromosome-arm losses to propose cancer-promoting pathway-level alterations. Integrating these findings highlights key candidate drivers that underlie the observed expression alterations, reinforcing their biological relevance. We provide a comprehensive catalog of candidate driver genes for recurrently lost chromosome-arms in human cancer.

Humans↗
PubMed1989

[Occupational exposure in cancer of the mouth, pharynx and larynx].

The AA. have scheduled a case-control study in order to assess the ambient hazards factors in these cancers, through the evaluation of its occupational risk. The program cover 242 cases of the epidermoid type of carcinoma (positive biopsy), and the group was parallelled with another group of 322 (after the age) admitted at the same Hospital, but affected with several processes. Were excluded the cancer of the lung, bladder, pancreas and kidney because of the causal link with tobacco smokers. In oral and pharyngeal cancer the AA. found out that the workers of high risk were butchers, blacksmiths, masons, drivers, electricians and railwaymen. Regarding the cancer of the larynx mechanics, plumbers, farmers, textile workers and drivers showed the greatest linkage. These findings are in accordance with those published in previous papers.

Adult↗
PubMed2000

[Carcinogenic effects of diesel emission: an epidemiological review].

The results of recent epidemiological studies and meta-analysis relating to carcinogenic effects of diesel emissions in exposed populations were reviewed. Statistical, but still not causal association between risk of lung cancer and occupational exposure to diesel emissions was found in a great number of studies under review. Long-term exposure to diesel exhausts (> 20 years) increases by 30-40% lung cancer risk in workers of the transport industry: truck drivers, diesel engine mechanics, locomotive engineers and brakesmen. The results are inconsistent among heavy equipment operators, bus drivers and miners. Relative risk of lung cancer among workers occupationally exposed to diesel emission may be comparable with that of environmental tobacco smoke. Further research is also needed in the area of carcinogenic mechanisms, and biomarkers of exposure should be developed and validated before reliable quantitative estimates of risk of harmful effects to the human health in occupational setting are made.

Adult↗
PubMed2000

Measurement of low levels of arsenic exposure: a comparison of water and toenail concentrations.

A study was conducted to evaluate toenail arsenic concentrations as a biologic marker of drinking water arsenic exposure. Study subjects were controls in a US population-based case-control study of nonmelanoma skin cancer, randomly selected from drivers' license records (those < 65 years of age) and Medicare enrollment files (those > or = 65 years of age). Between 1994 and 1997, a total of 540 controls were interviewed and toenail samples of sufficient weight were collected from 506 (93.7%) of these. Beginning in 1995, a sample of tap water was taken from the participants' homes; a total of 217 (98.6%) water samples were obtained from the 220 subjects interviewed. Arsenic determinations were made from toenail samples using neutron activation analysis. Water samples were analyzed using hydride-generation magnet sector inductively coupled mass spectrometry. Among 208 subjects with both toenail and water measurements, the correlation (r) between water and nail arsenic was 0.65 (p < 0.001) among those with water arsenic concentrations of 1 microg/liter or higher and 0.08 (p = 0.31) among those with concentrations below 1 microg/liter (overall r = 0.46, p < 0.001). Our data suggest that toenail samples provide a useful biologic marker for quantifying low-level arsenic exposure.

Adult↗
PubMed1994

Occupational risk factors for bladder cancer: results from a case-control study in Montreal, Quebec, Canada.

A population-based case-control study of the associations between various cancers and occupational exposures was carried out in Montreal, Quebec, Canada. Between 1979 and 1986, 484 persons with pathologically confirmed cases of bladder cancer and 1,879 controls with cancers at other sites were interviewed, as was a series of 533 population controls. The job histories of these subjects were evaluated by a team of chemist/hygienists for evidence of exposure to a list of 294 workplace chemicals, and information on relevant non-occupational confounders was obtained. On the basis of results of preliminary analyses and literature review, 19 occupations, 11 industries, and 23 substances were selected for in-depth multivariate analysis. Logistic regression analyses were carried out to estimate the odds ratio between each of these occupational circumstances and bladder cancer. There was weak evidence that the following substances may be risk factors for bladder cancer: natural gas combustion products, aromatic amines, cadmium compounds, photographic products, acrylic fibers, polyethylene, titanium dioxide, and chlorine. Among the substances evaluated which showed no evidence of an association were benzo(a)pyrene, leather dust, and formaldehyde. Several occupations and industries were associated with bladder cancer, including motor vehicle drivers and textile dyers.

Adult↗
PubMed1989

[Mortality in relation to the type of economic activity and occupation in the Turinese longitudinal study].

Occupational surveillance systems, which examine mortality patterns by occupation or industry, may contribute to hypothesis generation and priority setting for occupational cancer research and control. In the City of Torino the Local Population and Family Register records and the Census records are matchable through a computerized record linkage procedure. Since the early 1980's we have incorporated demographic events, occurring among residents, into the Census data source, covering birth, death and migration. This paper deals with the occupational mortality, from 1981 to 1985, of 262, 314 men and 146, 125 women, aged 15-64, who held a job at the 1981 Census. Mortality from 31 selected causes of death, including 22 cancer sites, among individuals employed in specific occupations (64 categories) and economic activities (80 categories) was compared with the mortality experienced by the whole cohort of active people. The surveillance design does not take into account potential confounders such as cigarette smoking, alcohol and previous work history. Despite the short duration of follow-up, some occupation-cancer associations, consistently documented in others surveillance studies, have been detected in our study: lung cancer among motor vehicle drivers (SMR 143, 27 obs), metal molders (SMR 178, 8 obs), welders (SMR 241, 7 obs) and wood workers (SMR 218, 12 obs), leukemias and electrical workers (SMR 367, 6 obs).

Adolescent↗
PubMed2026

Molecular characterization of salivary cancers: Patterns of genomic alterations and potential for impact on therapeutic choices.

BACKGROUND: Salivary cancers are rare malignancies with diverse histologies, molecular landscape, and limited effective systemic therapy options. Recent tumour genomics research has identified driver alterations in salivary gland cancers that have led to personalized therapy approaches. The primary objective was to perform molecular characterization using next generation sequencing (NGS) panel and evaluate the potential impact of results on clinical decision-making and treatment outcomes. METHODS: Patients with locally advanced or incurable metastatic salivary cancers suitable for systemic therapy underwent NGS tumour testing with an amplicon-based DNA/RNA NGS panel. Patient demographics, baseline characteristics, treatment and treatment outcomes were retrospectively collected. RESULTS: From 2021 to 2024, 58 advanced salivary cancer patients underwent molecular characterization of their tumour. Baseline characteristics at diagnosis: male 60%, median age 67, most common histologies; adenoid cystic 27%, salivary duct 19% and mucoepidermoid 12%. PIK3CA alterations were the most common molecular finding across all subtypes 22% (13/58) and were enriched in salivary duct carcinoma 73% (8/11). Other alterations identified were: ERBB2 (4), EGFR (2), HRAS (3), NTRK3 (2), BRAF p.V600E (1), and RET (1). Immunohistochemistry identified androgen receptor positivity across salivary cancer subtypes in 8/19 and HER2 positivity in 2/20 tested. Twenty-two patients received systemic therapy prior to NGS results for incurable/metastatic disease, first line treatments included 69% chemotherapy, 18% anti-androgen, 9% lenvatinib, 4% trial. CONCLUSION: Molecular characterization of salivary cancers identified targetable alterations in 37% of patients. The identification of potential therapeutic targets offers the opportunity for expanded treatment options to benefit salivary gland cancer patients.

Metastatic salivary gland cancer↗
PubMed2026

Comprehensive characterization of MET exon 14 skipping mutations in non-small cell lung cancer.

BACKGROUND: MET exon 14 skipping mutation (MET&#x394;ex14) is a key driver event in non-small cell lung cancer (NSCLC) and can emerge as an acquired drug resistance mechanism to MET, EGFR or ALK inhibitors. The clinical and genomic features of MET&#x394;ex14 in NSCLC require further characterization. METHODS: Our study included a total of 585 patients with MET&#x394;ex14&#x2009;+&#x2009;NSCLC, comprising 556 baseline samples, 53 samples from patients exhibiting resistance to MET inhibitors, and 16 samples from patients resistant to EGFR/ALK inhibitors. Genomic data from targeted next-generation sequencing (NGS) of tissue and/or plasma samples using GeneseeqPrime&#x2122; (a 425 pan-cancer gene panel) were analyzed. RESULTS: Overall, MET&#x394;ex14 exhibited a prevalence of 1.02% (n&#x2009;=&#x2009;585) in the screened NSCLC population, with a higher incidence in patients with a sarcomatoid histology. MET&#x394;ex14 was predominantly detected at the splice donor site, though the non-coding region adjacent to the splice acceptor site contributed considerably to the complexity of MET&#x394;ex14. Common concurrent alterations identified at baseline included those in TP53 (40.8%), CDK4 (16%) and EGFR (12.4%). Concurrent MET amplification and cell cycle pathway mutations were both associated with worse outcomes in patients treated with crizotinib, with significant co-occurrences observed also among these concurrent genomic variations. In addition, increased chromosomal instability and intra-tumoral heterogeneity correlated with a poorer response to crizotinib. Mechanisms of acquired resistance to MET inhibitors were primarily attributed to on-target MET D1228X/Y1230X mutations or off-target alterations within genes in the RTK/RAS/MAPK and PI3K/AKT/mTOR pathways. Intriguingly, our exploratory analysis also identified the FGFR3::TACC3 fusion as a potential resistance mechanism to savolitinib. Moreover, MET&#x394;ex14 was identified in 16 patients following progression on EGFR and ALK inhibitors, highlighting the need for developing tailored therapeutic strategies to overcome resistance. CONCLUSIONS: This study provides a comprehensive characterization of MET&#x394;ex14 in NSCLC, revealing its dual role as a primary driver of oncogenesis and a potential resistance mechanism to EGFR/ALK inhibitors. The identification of concurrent genetic alterations and potential resistance mechanisms enhances our molecular understanding of treatment responses. These findings highlight the need for further investigation into targeted therapies that consider the genomic complexity of MET&#x394;ex14 to improve treatment efficacy and patient outcomes.

Humans↗
PubMed2026

Enozertinib Is a Selective, Brain-Penetrant EGFR Inhibitor for Treating Non-Small Cell Lung Cancers with EGFR Exon 20 and Atypical Mutations.

UNLABELLED: EGFR mutations are common oncogenic drivers in non-small cell lung cancer (NSCLC), and approximately half of patients develop brain metastases over the course of their disease. Patients with nonclassic EGFR mutations, such as insertions in exon 20, are a high unmet need with a worse prognosis compared with patients with classic EGFR mutations. Here, we describe the discovery and development of enozertinib (formerly ORIC-114), a highly brain-penetrant, orally bioavailable, irreversible inhibitor that targets EGFR exon 20 mutations with unparalleled kinome selectivity. Preclinical studies revealed strong potency and tumor regressions driven by enozertinib across a broad range of atypical EGFR-mutant models. In a phase I clinical trial of enozertinib in patients with advanced NSCLC bearing atypical mutations in EGFR, a patient harboring an EGFR exon 20 insertion experienced sustained complete response of all systemic and brain metastases. Together, these findings identify enozertinib as a promising investigational inhibitor to address the unmet need for brain-penetrant therapies in NSCLC with EGFR exon 20 insertions or other atypical mutations. SIGNIFICANCE: Preclinical and initial phase I clinical data demonstrate the potency, kinome selectivity, efficacy, and brain penetration of enozertinib in NSCLC with EGFR exon 20 insertions and atypical mutations, warranting further clinical development.

Carcinoma, Non-Small-Cell Lung↗
PubMed2026

RHAMM drives formation of polyploid cancer cells and confers resistance to ER-targeted therapy in breast cancer.

Endocrine resistance in ER+ breast cancer remains a major clinical challenge. Here, we identify RHAMM as a key driver of resistance by orchestrating polyploid cancer cell (PCC) formation. Single-cell transcriptomics uncovered a G2/M-enriched, RHAMM+ subpopulation in endocrine-resistant tumors. Mechanistically, RHAMM binds Septin9/10 to promote aberrant cytoskeleton polymerization, activating YAP independent of Hippo signaling, which induces cytokinesis failure and facilitates PCC generation. Concurrently, RHAMM destabilizes p21 mRNA, enabling cell cycle progression despite genomic instability. The RHAMM-p21 axis serves as a bypass mechanism supporting polyploidization. Upon endocrine treatment, RHAMM is transcriptionally up-regulated by Slug. Clinically, RHAMMhigh signatures are enriched in metastatic and recurrent ER+ tumors and correlate with poor prognosis, highlighting its therapeutic relevance. Importantly, targeting RHAMM or YAP abrogates PCC formation and restores fulvestrant sensitivity. These findings reveal RHAMM-mediated polyploidization as an adaptive mechanism underlying endocrine resistance, suggesting the therapeutic potential of targeting the RHAMM-YAP axis.

Humans↗
PubMed2005

Truck drivers and heart disease in the United States, 1979-1990.

BACKGROUND: Studies of truck drivers and cardiovascular disease (CVD), myocardial infarction, or ischemic heart disease (IHD) are limited, although studies of other professional drivers reported increased risk. METHODS: US mortality data from 1979 to 1990 for ages 15-90 were used to calculate proportional mortality ratios (PMRs) for heart disease and lung cancer for short and long haul truck drivers. Analysis was performed for Black (998 short haul and 13,241 long haul) truck drivers and White (4,929 short and 74,315 long haul) truck drivers separately. RESULTS: The highest significantly elevated proportionate heart disease (IHD, acute myocardial infarction (AMI), and other forms of heart disease) and lung cancer mortality was found for White and Black male long haul truck drivers age 15-54. Mortality was not significantly elevated for short haul truck drivers of either race or gender, nor for truck drivers who died after age 65, except for lung cancer among White males. An indirect adjustment suggested that smoking could explain the excess IHD mortality, but no direct data for smoking or the other known risk factors for heart disease were available and occupational exposures were not measured. CONCLUSIONS: The highest significant excess proportionate mortality for lung cancer, IHD and AMI was found for long haul truck drivers who were under age 55 at death. A cohort or longitudinal study of heart disease among long haul truck drivers, that obtains data for occupational exposures as well as lifestyle risk factors, could help explain inconsistencies between the findings of this and previous studies.

Adolescent↗